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Desulfurization of thiosemicarbazones: the role of metal ions and biological implications

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Abstract

Thiosemicarbazones are biologically active substances whose structural formula is formed by an azomethine, an hydrazine, and a thioamide fragments, to generate a R2C=N–NR–C(=S)–NR2 backbone. These compounds often act as ligands to generate highly stable metal–organic complexes. In certain experimental conditions, however, thiosemicarbazones undergo reactions leading to the cleavage of the chain. Sometimes, the breakage involves desulfurization processes. The present work summarizes the different chemical factors that influence the desulfurization reactions of thiosemicarbazones, such as pH, the presence of oxidant reactants or the establishment of redox processes as those electrochemically induced, the effects of the solvent, the temperature, and the electromagnetic radiation. Many of these reactions require coordination of thiosemicarbazones to metal ions, even those present in the intracellular environment. The nature of the products generated in these reactions, their detection in vivo and in vitro, together with the relevance for the biological activity of these compounds, mainly as antineoplastic agents, is discussed.

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References

  1. Gingras BA, Somorjai RI, Bayley CH (1961) The preparation of some thiosemicarbazones and their copper complexes. Can J Chem 39:973–985. https://doi.org/10.1139/v61-122

    Article  CAS  Google Scholar 

  2. Benns BG, Gingras BA, Bayley CH (1960) Antifungal activity of some thiosemicarbazones and their copper complexes. Appl Microbiol 8:353–356. https://doi.org/10.1128/am.8.6.353-356.1960

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Singh RB, Ishii H (1991) Analytical potentialities of thiosemicarbazones and semicarbazones. Crit Rev Anal Chem 22:381–409. https://doi.org/10.1080/10408349108051640

    Article  CAS  Google Scholar 

  4. Arion VB (2019) Coordination chemistry of S-substituted isothiosemicarbazides and isothiosemicarbazones. Coord Chem Rev 387:348–397. https://doi.org/10.1016/j.ccr.2019.02.013

    Article  CAS  Google Scholar 

  5. González-Barcia LM, Romero MJ, González-Noya AM, Bermejo MR, Maneiro M, Zaragoza G, Pedrido R (2016) “The Golden Method”: electrochemical synthesis is an efficient route to gold complexes. Inorg Chem 55:7823–7825. https://doi.org/10.1021/acs.inorgchem.6b01362

    Article  CAS  PubMed  Google Scholar 

  6. González-Barcia LM, Fernández-Fariña S, Rodríguez-Silva L, Bermejo MR, González-Noya AM, Pedrido R (2020) Comparative study of the antitumoral activity of phosphine-thiosemicarbazone gold(I) complexes obtained by different methodologies. J Inorg Biochem 203:110931–110940. https://doi.org/10.1016/j.jinorgbio.2019.110931

    Article  CAS  PubMed  Google Scholar 

  7. Lobana TS, Sharma R, Bawa G, Khanna S (2009) Bonding and structure trends of thiosemicarbazone derivatives of metals—an overview. Coord Chem Rev 253:977–1055. https://doi.org/10.1016/j.ccr.2008.07.004

    Article  CAS  Google Scholar 

  8. Osman UM, Silvarajoo S, Kamarudin KH, Tahir MIM, Kwong HC (2021) Ni(II) complex containing a thiosemicarbazone ligand: synthesis, spectroscopy, single-crystal X-ray crystallographic and conductivity studies. J Mol Struct 1223:128994. https://doi.org/10.1016/j.molstruc.2020.128994

    Article  CAS  Google Scholar 

  9. Macalik L, Pyrkosz-Bulska M, Małecki G, Hermanowicz K, Solarz P, Janczak J, Hanuza J (2021) Synthesis, structural and spectroscopic properties of [N′-[(2,4-dihydroxyphenyl) methylidene]-4-(4-fluorophenyl) piperazine-1-carbothiohydrazide] thiosemicarbazone and its terbium complex. Inorg Chem Commun 123:108351. https://doi.org/10.1016/j.inoche.2020.108351

    Article  CAS  Google Scholar 

  10. Yousef TA, Abu El-Reash GM (2020) Synthesis, and biological evaluation of complexes based on thiosemicarbazone ligand. J Mol Struct 1201:127180. https://doi.org/10.1016/j.molstruc.2019.127180

    Article  CAS  Google Scholar 

  11. West DX, Liberta AE, Yerande RG (1993) Thiosemicarbazone complexes of copper(II): structural and biological studies. Coord Chem Rev 123:49–71

    Article  CAS  Google Scholar 

  12. Beiles RH, Calvin M (1947) The oxygen-carrying synthetic chelate compounds. VII. Preparation. J Am Chem Soc 69:1886–1893. https://doi.org/10.1021/ja01200a013

    Article  Google Scholar 

  13. Al-Jeboori M, Dawood AH (2008) Synthesis and structural studies of novel 2,6-diformyl-p-cresol bis-(thiosemicarbazone) ligand and their binuclear complexes with Ni+2, Pd+2, Zn+2, Cd+2 and Hg+2 metal ions. J Kerbala Univ 6:133–143

    Google Scholar 

  14. Chandra S, Sangeetika C, Rathi A (2001) Magnetic and spectral studies on copper(II) complexes of NO and NS donor ligands. J Saudi Chem Soc 5:175–182

    CAS  Google Scholar 

  15. Sahin M, Bal-Demirci T, Pozan-Soylu G, Ülküseven B (2009) Synthesis, characterization and thermal decomposition of dioxouranium(VI) complexes with N1,N4-diarylidene-S-propyl-thiosemicarbazone: crystal structure of [UO2(LI)(C4H9OH)]. Inorg Chim Acta 362:2407–2412. https://doi.org/10.1016/j.ica.2008.10.036

    Article  CAS  Google Scholar 

  16. Ferrari MB, Bisceglie F, Pelosi G, Tarasconi P, Albertini R, Dall’Aglio PP, Pinelli S, Bergamo A, Sava G (2004) Synthesis, characterization and biological activity of copper complexes with pyridoxal thiosemicarbazone derivatives. X-ray crystal structure of three dimeric complexes. J Inorg Biochem 98:301–312. https://doi.org/10.1016/j.jinorgbio.2003.09.011

    Article  CAS  Google Scholar 

  17. Christlieb M, Dilworth JR (2016) Ligands for molecular imaging: the synthesis of bis(thiosemicarbazone) ligands. Chem Eur J 12:6194–6206. https://doi.org/10.1002/chem.200501069

    Article  CAS  Google Scholar 

  18. Hałdys K, Latajka R (2019) Thiosemicarbazones with tyrosinase inhibitory activity. MedChemComm 10:378–389. https://doi.org/10.1039/c9md00005d

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Paterson BM, Donnelly PS (2011) Copper complexes of bis(thiosemicarbazones): from chemotherapeutics to diagnostic and therapeutic radiopharmaceuticals. Chem Soc Rev 40:3005–3018. https://doi.org/10.1039/c0cs00215a

    Article  CAS  PubMed  Google Scholar 

  20. Gupta S, Singh N, Khan T, Joshi S (2022) Thiosemicarbazone derivatives of transition metals as multi-target drugs: a review. Results Chem 4:100459. https://doi.org/10.1016/j.rechem.2022.100459

    Article  CAS  Google Scholar 

  21. French FA, Blanz EJ Jr (1965) The carcinostatic activity of α-(N) heterocyclic carboxaldehyde thiosemicarbazones: I. Isoquinoline-1-carboxaldehyde thiosemicarbazone. Can Res 25:1454–1458

    CAS  Google Scholar 

  22. Campbell MJM (1975) Transition metal complexes of thiosemicarbazide and thiosemicarbazones. Coord Chem Rev 15:279–319. https://doi.org/10.1016/S0010-8545(00)80276-3

    Article  CAS  Google Scholar 

  23. Padhyé S, Kauffman GB (1985) Transition metal complexes of semicarbazones and thiosemicarbazones. Coord Chem Rev 63:127–160. https://doi.org/10.1016/0010-8545(85)80022-9

    Article  Google Scholar 

  24. Casas JS, García-Tasende MS, Sordo J (2000) Main group metal complexes of semicarbazones and thiosemicarbazones. A structural review. Coord Chem Rev 209:197–261. https://doi.org/10.1016/S0010-8545(00)00363-5

    Article  CAS  Google Scholar 

  25. Quiroga AG, Ranninger CN (2004) Contribution to the SAR field of metallated and coordination complexes: studies of the palladium and platinum derivatives with selected thiosemicarbazones as antitumoral drugs. Coord Chem Rev 248:119–133. https://doi.org/10.1016/j.cct.2003.11.004

    Article  CAS  Google Scholar 

  26. Devi J, Kumar B, Taxak B (2022) Recent advancements of organotin(IV) complexes derived from hydrazone and thiosemicarbazone ligands as potential anticancer agents. Inorg Chem Commun 139:109208. https://doi.org/10.1016/j.inoche.2022.109208

    Article  CAS  Google Scholar 

  27. Kalinowski DS, Quach P, Richardson DR (2009) Thiosemicarbazones: the new wave in cancer treatment. Fut Med Chem 1:1143–1151. https://doi.org/10.4155/fmc.09.80

    Article  CAS  Google Scholar 

  28. Yu Y, Kalinowski DS, Kovacevic Z, Siafakas AR, Jansson PJ, Stefani C, Lovejoy DB, Sharpe PC, Bernhardt PV, Richardson DR (2009) Thiosemicarbazones from the old to new: iron chelators that are more than just ribonucleotide reductase inhibitors. J Med Chem 52:5271–5294. https://doi.org/10.1021/jm900552r

    Article  CAS  PubMed  Google Scholar 

  29. Parrilha GL, dos Santos RG, Beraldo H (2022) Applications of radiocomplexes with thiosemicarbazones and bis(thiosemicarbazones) in diagnostic and therapeutic nuclear medicine. Coord Chem Rev 458:214418. https://doi.org/10.1016/j.ccr.2022.214418

    Article  CAS  Google Scholar 

  30. Dilworth JR, Hueting R (2012) Metal complexes of thiosemicarbazones for imaging and therapy. Inorg Chim Acta 389:3–15. https://doi.org/10.1016/j.ica.2012.02.019

    Article  CAS  Google Scholar 

  31. Eram Jamal S, Iqbal A, Abdul Rahman K, Tahmeena K (2019) Thiosemicarbazone complexes as versatile medicinal chemistry agents: a review. J Drug Deliv Therap 9:689–703. https://doi.org/10.22270/jddt.v9i3.2888

    Article  CAS  Google Scholar 

  32. Bajaj K, Buchanan RM, Grapperhaus CA (2021) Antifungal activity of thiosemicarbazones, bis(thiosemicarbazones), and their metal complexes. J Inorg Biochem 225:111620. https://doi.org/10.1016/j.jinorgbio.2021.111620

    Article  CAS  PubMed  Google Scholar 

  33. Moorthy SHN, Cerqueira MFSA, Ramos J, Fernandes A (2013) Aryl- and heteroaryl-thiosemicarbazone derivatives and their metal complexes: a pharmacological template. Recent Pat Anticancer Drug Discov 8:168–182. https://doi.org/10.2174/1574892811308020005

    Article  CAS  PubMed  Google Scholar 

  34. Matesanz AI, Caballero AB, Lorenzo C, Espargaró A, Sabaté R, Quiroga AG, Gamez P (2020) Thiosemicarbazone derivatives as inhibitors of amyloid-β aggregation: effect of metal coordination. Inorg Chem 59:6978–6987. https://doi.org/10.1021/acs.inorgchem.0c00467

    Article  CAS  PubMed  Google Scholar 

  35. Bormio Nunes JH, Hager S, Mathuber M, Pósa V, Roller A, Enyedy EA, Stefanelli A, Berger W, Keppler BK, Heffeter P, Kowol CR (2020) Cancer cell resistance against the clinically investigated thiosemicarbazone COTI-2 is based on formation of intracellular copper complex glutathione adducts and ABCC1-mediated efflux. J Med Chem 63:13719–13732. https://doi.org/10.1021/acs.jmedchem.0c01277

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Beraldo H, Gambino D (2004) The wide pharmacological versatility of semicarbazones, thiosemicarbazones and their metal complexes. Mini Rev Med Chem 4:31–39. https://doi.org/10.2174/1389557043487484

    Article  CAS  PubMed  Google Scholar 

  37. Pahontu E, Julea F, Rosu T, Purcarea V, Chumakov Y, Petrenco P, Gulea A (2015) Antibacterial, antifungal and in vitro antileukaemia activity of metal complexes with thiosemicarbazones. J Cell Mol Med 19:865–878. https://doi.org/10.1111/jcmm.12508

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Matesanz AI, Herrero JM, Quiroga AG (2021) Chemical and biological evaluation of thiosemicarbazone-bearing heterocyclic metal complexes. Curr Top Med Chem 21:59–72. https://doi.org/10.2174/1568026620666201022144004

    Article  CAS  PubMed  Google Scholar 

  39. Braga SFP, Santos VC, Vieira RP, da Silva EB, Monti L, Krake SH, Martinez PDG, Dias LC, Caffrey CR, Siqueira-Neto JL, Oliveira RB, Ferreira RS (2022) From rational design to serendipity: discovery of novel thiosemicarbazones as potent trypanocidal compounds. Eur J Med Chem 244:114876. https://doi.org/10.1016/j.ejmech.2022.114876

    Article  CAS  PubMed  Google Scholar 

  40. Beraldo H (2004) Semicarbazonas e tiosemicarbazonas: o amplo perfil farmacológico e usos clínicos. Quim Nova 27:461–471. https://doi.org/10.1590/S0100-40422004000300017

    Article  CAS  Google Scholar 

  41. Matesanz AI, Souza P (2009) α-N-heterocyclic thiosemicarbazone derivatives as potential antitumor agents: a structure–activity relationships approach. Mini Rev Med Chem 9:1389–1396. https://doi.org/10.2174/138955709789957422

    Article  CAS  PubMed  Google Scholar 

  42. García-Tojal J, Gil-García R, Gómez-Saiz P, Ugalde M (2011) Pyridine-2-carbaldehyde thiosemicarbazonecopper system: extending some findings to other thiosemicarbazone and coordination compounds. Curr Inorg Chem 1:189–210. https://doi.org/10.2174/1877944111101020189

    Article  Google Scholar 

  43. Domagk G, Behnisch R, Mietzsch F, Schmidt H (1946) Uber eine neuo, gegen tuberketbazillen in vitro wirk- same verbindungsklasse. Naturwissenschaften 33:315. https://doi.org/10.1007/BF00624524

    Article  CAS  Google Scholar 

  44. Hickey JL, Lim S, Hayne DJ, Paterson BM, White M, Villemagne VL, Roselt P, Binns D, Cullinane C, Jeffery CM, Price RI, Barnham KJ, Donnelly PS (2013) Diagnostic imaging agents for Alzheimer’s disease: copper radiopharmaceuticals that target Aβ plaques. J Am Chem Soc 135:16120–16132. https://doi.org/10.1021/ja4057807

    Article  CAS  PubMed  Google Scholar 

  45. Hickey JL, Crouch PJ, Mey S, Caragounis A, White JM, White AR, Donnelly PS (2011) Copper(II) complexes of hybrid hydroxyquinoline-thiosemicarbazone ligands: GSK3β inhibition due to intracellular delivery of copper. Dalton Trans 40:1338–1347. https://doi.org/10.1039/C0DT01176B

    Article  CAS  PubMed  Google Scholar 

  46. Bauer DJ, Stvincent L, Kempe CH, Downie AW (1963) Prophylactic treatment of small pox contacts with N-methylisatin beta-thiosemicarbazone (compound 33T57, Marboran). Lancet 2:494–496. https://doi.org/10.1016/S0140-6736(63)90230-7

    Article  CAS  PubMed  Google Scholar 

  47. Molter A, Rust J, Lehmann CW, Deepa G, Chiba P, Mohr F (2011) synthesis, structures and anti-malaria activity of some gold(I) phosphine complexes containing seleno- and thiosemicarbazonato ligands. Dalton Trans 40:9810–9820. https://doi.org/10.1039/C1DT10885A

    Article  CAS  PubMed  Google Scholar 

  48. Lobana TS (2015) Activation of C-H bonds of thiosemicarbazones by transition metals: synthesis, structures and importance of cyclometallated compounds. RSC Adv 5:37231–37274. https://doi.org/10.1039/C5RA03333K

    Article  CAS  Google Scholar 

  49. Salas PF, Herrmann C, Orvig C (2013) Metalloantimalarials. Chem Rev 113:3450–3492. https://doi.org/10.1021/cr3001252

    Article  CAS  PubMed  Google Scholar 

  50. Cipriani M, Toloza J, Bradford L, Putzu E, Vieites M, Curbelo E, Tomaz AI, Garat B, Guerrero J, Gancheff JS, Maya JD, Azar CO, Gambino D, Otero L (2014) Effect of the metal ion on the anti T. cruzi activity and mechanism of action of 5-nitrofuryl-containing thiosemicarbazone metal complexes. Eur J Inorg Chem 2014:4677–4689. https://doi.org/10.1002/ejic.201402614

    Article  CAS  Google Scholar 

  51. Netalkar PP, Netalkar SP, Revankar VK (2015) Transition metal complexes of thiosemicarbazone: synthesis, structures and invitro antimicrobial studies. Polyhedron 100:215–222. https://doi.org/10.1016/j.poly.2015.07.07

    Article  CAS  Google Scholar 

  52. Argibay-Otero S, Gano L, Fernandes C, Paulo A, Carballo R, Vázquez-López EM (2020) Chemical and biological studies of Re(I)/Tc(I) thiosemicarbazonate complexes relevant for the design of radiopharmaceuticals. J Inorg Biochem 203:110917. https://doi.org/10.1016/j.jinorgbio.2019.110917

    Article  CAS  PubMed  Google Scholar 

  53. Brockman RW, Thomson JR, Bell MJ, Skipper HE (1956) Observations on the antileukemic activity of pyridine- 2-carboxaldehyde thiosemicarbazone and thiocarbohydrazone. Cancer Res 16:167–170

    CAS  PubMed  Google Scholar 

  54. King AP, Gellineau HA, Ahn JE, MacMillan SN, Wilson JJ (2017) Bis(thiosemicarbazone) Complexes of cobalt(III). Synthesis, characterization, and anticancer potential. Inorg Chem 56:6609–6623. https://doi.org/10.1021/acs.inorgchem.7b00710

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Arora S, Agarwal S, Singhal S (2014) Anticancer activities of thiosemicarbazides/thiosemicarbazones: a review. Int J Pharm Pharm Sci 6:34–41

    CAS  Google Scholar 

  56. Jansson PJ, Kalinowski DS, Lane DJR, Kovacevic Z, Seebacher NA, Fouani L, Sahni S, Merlot AM, Richardson DR (2015) The renaissance of polypharmacology in the development of anti-cancer therapeutics: inhibition of the “triad of death” in cancer by di-2-pyridylketone thiosemicarbazones. Pharmacol Res 100:255–260. https://doi.org/10.1016/j.phrs.2015.08.013

    Article  CAS  PubMed  Google Scholar 

  57. Salehi R, Abyar S, Ramazani F, Khandar AA, Hosseini-Yazdi SA, White JM, Edalati M, Kahroba H, Talebi M (2022) Enhanced anticancer potency with reduced nephrotoxicity of newly synthesized platin-based complexes compared with cisplatin. Sci Rep 12:8316. https://doi.org/10.1038/s41598-022-11904-3

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Mrozek-Wilczkiewicz A, Serda M, Musiol R, Malecki G, Szurko A, Muchowicz A, Golab J, Ratuszna A, Polanski J (2014) Iron chelators in photodynamic therapy revisited: synergistic effect by novel highly active thiosemicarbazones. ACS Med Chem Lett 5:336–339. https://doi.org/10.1021/ml400422a

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Stefani C, Jansson PJ, Gutierrez E, Bernhardt PV, Richardson DR, Kalinowski DS (2013) Alkyl substituted 2′-benzoylpyridine thiosemicarbazone chelators with potent and selective anti-neoplastic activity: novel ligands that limit methemoglobin formation. J Med Chem 56:357–370. https://doi.org/10.1021/jm301691s

    Article  CAS  PubMed  Google Scholar 

  60. Shao J, Ma ZY, Li A, Liu YH, Xie CZ, Qiang ZY, Xu JY (2014) Thiosemicarbazone Cu(II) and Zn(II) complexes as potential anticancer agents: syntheses, crystal structure, DNA cleavage, cytotoxicity and apoptosis induction activity. J Inorg Biochem 136:13–23. https://doi.org/10.1016/j.jinorgbio.2014.03.004

    Article  CAS  PubMed  Google Scholar 

  61. Palanimuthu D, Shinde SV, Somasundaram K, Samuelson AG (2013) In vitro and in vivo anticancer activity of copper bis(thiosemicarbazone) complexes. J Med Chem 56:722–734. https://doi.org/10.1021/jm300938r

    Article  CAS  PubMed  Google Scholar 

  62. Bisceglie F, Pinelli S, Alinovi R, Tarasconi P, Buschini A, Mussi F, Mutti A, Pelosi G (2012) Copper(II) thiosemicarbazonate molecular modifications modulate apoptotic and oxidative effects on U937 cell line. J Inorg Biochem 116:195–203. https://doi.org/10.1016/j.jinorgbio.2012.07.006

    Article  CAS  PubMed  Google Scholar 

  63. Hall MD, Brimacombe KR, Varonka MS, Pluchino KM, Monda JK, Li J, Walsh MJ, Boxer MB, Warren TH, Gales HM, Gottesman MM (2011) Synthesis and structure-activity evaluation of isatin-β-thiosemicarbazones with improved selective activity toward multidrug-resistant cells expressing P-glycoprotein. J Med Chem 54:5878–5889. https://doi.org/10.1021/jm2006047

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Prabhakaran R, Kalaivani P, Huang R, Poornima P, Padma VV, Dallemer F, Natarajan K (2013) DNA binding, antioxidant, cytotoxicity (MTT, lactate dehydrogenase, NO), and cellular uptake studies of structurally different nickel(II) thiosemicarbazone complexes: synthesis, spectroscopy, electrochemistry, and X-ray crystallography. J Biol Inorg Chem 18:233–247. https://doi.org/10.1007/s00775-012-0969-x

    Article  CAS  PubMed  Google Scholar 

  65. Kovacevic Z, Chikhani S, Lovejoy DB, Richardson DR (2011) Novel thiosemicarbazone iron chelators induce up-regulation and phosphorylation of the metastasis suppressor N-myc down-stream regulated gene 1: a new strategy for the treatment of pancreatic cancer. Mol Pharmacol 80:598–609. https://doi.org/10.1124/mol.111.073627

    Article  CAS  PubMed  Google Scholar 

  66. Milunovic MNM, Enyedy ÉA, Nagy NV, Kiss T, Trondl R, Jakupec MA, Keppler BK, Krachler R, Novitchi G, Arion VB (2012) L- and D-proline thiosemicarbazone conjugates: coordination behavior in solution and the effect of copper(II) coordination on their antiproliferative activity. Inorg Chem 51:9309–9321. https://doi.org/10.1021/ic300967j

    Article  CAS  PubMed  Google Scholar 

  67. Dixon KM, Lui GYL, Kovacevic Z, Zhang D, Yao M, Chen Z, Dong Q, Assinder SJ, Richardson DR (2013) Dp44mT targets the AKT, TGF-β and ERK pathways via the metastasis suppressor NDRG1 in normal prostate epithelial cells and prostate cancer cells. Br J Cancer 108:409–419. https://doi.org/10.1038/bjc.2012.582

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Qi J, Liang S, Gou Y, Zhang Z, Zhou Z, Yang F, Liang H (2015) Synthesis of four binuclear copper(II) complexes: structure, anticancer properties and anticancer mechanism. Eur J Med Chem 96:360–368. https://doi.org/10.1016/j.ejmech.2015.04.031

    Article  CAS  PubMed  Google Scholar 

  69. Menezes SV, Sahni S, Kovacevic Z, Richardson DR (2017) Interplay of the iron-regulated metastasis suppressor NDRG1 with epidermal growth factor receptor (EGFR) and oncogenic signaling. J Biol Chem 292:12772–12782. https://doi.org/10.1074/jbc.R117.776393

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Zou BQ, Lu X, Qin QP, Bai YX, Zhang Y, Wang M, Liu YC, Chen ZF, Liang H (2017) Three novel transition metal complexes of 6-methyl-2-oxo-quinoline-3-carbaldehyde thiosemicarbazone: synthesis, crystal structure, cytotoxicity, and mechanism of action. RSC Adv 7:17923–17933. https://doi.org/10.1039/C7RA00826K

    Article  CAS  Google Scholar 

  71. Brodowska K, Correia I, Garribba E, Marques F, Klewicka E, Lodyga-Chruscińska E, Pessoa JC, Dzeikala A, Chrusciński L (2016) Coordination ability and biological activity of a naringenin thiosemicarbazone. J Inorg Biochem 165:36–48. https://doi.org/10.1016/j.jinorgbio.2016.09.014

    Article  CAS  PubMed  Google Scholar 

  72. Basha MT, Bordini J, Richardson DR, Martinez M, Bernhardt PV (2016) Kinetico-mechanistic studies on methemoglobin generation by biologically active thiosemicarbazone iron(III) complexes. J Inorg Biochem 162:326333. https://doi.org/10.1016/j.jinorgbio.2015.12.004

    Article  CAS  Google Scholar 

  73. Pape VFS, Tóth S, Füredi A, Szebényi K, Lovrics A, Szabó P, Wiese M, Szakács G (2016) Design, synthesis, and biological evaluation of thiosemicarbazones, hydrazinobenzothiazoles and arylhydrazones as anticancer agents with a potential to overcome multidrug resistance. Eur J Med Chem 117:335–354. https://doi.org/10.1016/j.ejmech.2016.03.078

    Article  CAS  PubMed  Google Scholar 

  74. Myers CR (2016) Enhanced targeting of mitochondrial peroxide defense by the combined use of thiosemicarbazones and inhibitors of thioredoxin reductase. Free Radic Biol Med 91:81–92. https://doi.org/10.1016/j.freeradbiomed.2015.12.008

    Article  CAS  PubMed  Google Scholar 

  75. Fu Y, Liu Y, Wang J, Li C, Zhou S, Yang Y, Zhou P, Lu C, Li C (2017) Calcium release induced by 2-pyridinecarboxaldehyde thiosemicarbazone and its copper complex contributes to tumor cell death. Oncol Rep 37:1662–1670. https://doi.org/10.3892/or.2017.5395

    Article  CAS  PubMed  Google Scholar 

  76. French FA, Blanz EJ (1966) The carcinostatic activity of thiosemicarbazones of formyl heteroaromatic compounds.1 III. Primary correlation. J Med Chem 9:585–589. https://doi.org/10.1021/jm00322a032

    Article  CAS  PubMed  Google Scholar 

  77. Agrawal KC, Sartorelli AC (1975) Alpha-(N)-heterocyclic carboxaldehyde thiosemicarbazones. In: Sartorelli AC, Johns DG (eds) Handbook of experimental pharmacology. Springer, Berlin, pp 793–807

    Google Scholar 

  78. Sartorelli AC, Agrawal KC, Tsiftsoglou AS, Moore EC (1977) Characterization of the biochemical mechanism of action of α-(N)-heterocyclic carboxaldehyde thiosemicarbazones. Adv Enzyme Regul 15:117–139. https://doi.org/10.1016/0065-2571(77)90012-7

    Article  CAS  Google Scholar 

  79. Kunos CA, Ivy SP (2018) Triapine radiochemotherapy in advanced stage cervical cancer. Front Oncol 8:149–155. https://doi.org/10.3389/fonc.2018.00149

    Article  PubMed  PubMed Central  Google Scholar 

  80. Kolesar J, Brundage RC, Pomplun M, Alberti D, Holen K, Traynor A, Ivy P, Wilding G (2011) Population pharmacokinetics of 3-aminopyridine-2-carboxaldehyde thiosemicarbazone (Triapine®) in cancer patients. Cancer Chemother Pharmacol 67:393–400. https://doi.org/10.1007/s00280-010-1331-z

    Article  CAS  PubMed  Google Scholar 

  81. Miah AB, Harrington KJ, Nutting CM (2010) Triapine® in clinical practice. Eur J Clin Med Oncol 2:87–92

    Google Scholar 

  82. Guo ZL, Richardson DR, Kalinowski DS, Kovacevic Z, Tan-Un KC, Chan GCF (2016) The novel thiosemicarbazone, di-2-pyridylketone 4-cyclohexyl-4-methyl-3-thiosemicarbazone (DpC), inhibits neuroblastoma growth in vitro and in vivo via multiple mechanisms. J Hematol Oncol 9:98–114. https://doi.org/10.1186/s13045-016-0330-x

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  83. Serda M, Kalinowski DS, Rasko N, Potučková E, Mrozek-Wilczkiewicz A, Musiol R, Małecki JG, Sajewicz M, Ratuszna A, Muchowicz A, Gołąb J, Šimunek T, Richardson DR, Polanski J (2014) Exploring the anti-cancer activity of novel thiosemicarbazones generated through the combination of retro-fragments: dissection of critical structure-activity relationships. PLoS ONE 9:e110291. https://doi.org/10.1371/journal.pone.0110291

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  84. https://clinicaltrials.gov/ct2/show/NCT02688101?term=DpC&draw=2&rank=1. Accessed 21 June 2023

  85. https://clinicaltrials.gov/ct2/show/NCT02433626?term=thiose-micarbazone&draw=2&rank=9. Accessed 21 June 2023

  86. https://classic.clinicaltrials.gov/ct2/show/NCT02466971?term=thiosemicarbazone&draw=2. Accessed 21 June 2023

  87. Sartorelli AC, Booth BA (1967) Inhibition of the growth of sarcoma 180 ascites cells by combinations of inhibitors of nucleic acid biosynthesis and the cupric chelate of kethoxal bis-(thiosemicarbazone). Can Res 27:1614–1619

    CAS  Google Scholar 

  88. Nutting CM, van Herpen CML, Miah AB (2009) Phase II study of 3-AP Triapine in patients with recurrent or metastatic head and neck squamous cell carcinoma. Ann Oncol 20:1275–1279. https://doi.org/10.1093/annonc/mdn775

    Article  CAS  PubMed  Google Scholar 

  89. Ma B, Goh BC, Tan EH, Lam KC, Soo R, Leong SS, Wang LZ, Mo F, Chan ATC, Zee B, Mok T (2008) A multicenter phase II trial of 3-aminopyridine-2-carboxaldehyde thiosemicarbazone (3-AP, Triapine®) and gemcitabine in advanced non-small-cell lung cancer with pharmacokinetic evaluation using peripheral blood mononuclear cells. Invest New Drugs 26:169–173. https://doi.org/10.1007/s10637-007-9085-0

    Article  CAS  PubMed  Google Scholar 

  90. Priyarega S, Haribabu J, Karvembu R (2022) Development of thiosemicarbazone-based transition metal complexes as homogeneous catalysts for various organic transformations. Inorg Chim Acta 532:120742. https://doi.org/10.1016/j.ica.2021.120742

    Article  CAS  Google Scholar 

  91. Gil-García R, Ugalde M, Busto N, Lozano HJ, Leal JM, Pérez B, Madariaga G, Insausti M, Lezama L, Sanz R, Gómez-Sainz LM, García B, García-Tojal J (2016) Selectivity of a thiosemicarbazonatocopper(II) complex towards duplex RNA. Relevant noncovalent interactions both in solid state and solution. Dalton Trans 45:18704–18718. https://doi.org/10.1039/C6DT02907H

    Article  CAS  PubMed  Google Scholar 

  92. Ruiz R, García B, García-Tojal J, Busto N, Ibeas S, Leal JM, Martins C, Gaspar J, Borras J, Gil-García R, González-Álvarez M (2010) Biological assays and noncovalent interactions of pyridine-2-carbaldehyde thiosemicarbazonecopper(II) drugs with [poly(dA–dT)]2, [poly(dG–dC)]2, and calf thymus DNA. J Biol Inorg Chem 15:515–532. https://doi.org/10.1007/s00775-009-0620-7

    Article  CAS  PubMed  Google Scholar 

  93. Saswati CA, Dash SP, Panda AK, Acharyya R, Biswas A, Mukhopadhyay S, Crochet A, Patil YP, Nethaji M, Dinda R (2015) Synthesis, X-ray structure and in vitro cytotoxicity studies of Cu(I/II) complexes of thiosemicarbazone: special emphasis on their interactions with DNA. Dalton Trans 44:6140–6157. https://doi.org/10.1039/C4DT03764B

    Article  CAS  PubMed  Google Scholar 

  94. Muralisankar M, Bhuvanesh NSP, Sreekanth A (2016) Synthesis, X-ray crystal structure, DNA/protein binding and DNA cleavage studies of novel copper(II) complexes of N-substituted isatin thiosemicarbazone ligands. New J Chem 40:2661–2679. https://doi.org/10.1039/C5NJ02806J

    Article  CAS  Google Scholar 

  95. Lessa JA, Guerra JC, Miranda LF, Romeiro CFD, Da Silva JG, Mendes IC, Speziali NL, Souza-Fagundes EM, Beraldo H (2011) Gold(I) complexes with thiosemicarbazones: cytotoxicity against human tumor cell lines and inhibition of thioredoxin reductase activity. J Inorg Biochem 105:1729–1739. https://doi.org/10.1016/j.jinorgbio.2011.09.008

    Article  CAS  PubMed  Google Scholar 

  96. Myers JM, Cheng Q, Antholine WE, Kalyanaraman B, Filipovska A, Arnér ESJ, Myers CR (2013) Redox activation of Fe(III)–thiosemicarbazones and Fe(III)–bleomycin by thioredoxin reductase: specificity of enzymatic redox centers and analysis of reactive species formation by ESR spin trapping. Free Radic Biol Med 60:183–194. https://doi.org/10.1016/j.freeradbiomed.2013.02.016

    Article  CAS  PubMed  Google Scholar 

  97. Leigh M, Raines DJ, Castillo CE, Duhme-Klair AK (2011) Inhibition of xanthine oxidase by thiosemicarbazones, hydrazones and dithiocarbazates derived from hydroxy-substituted benzaldehydes. ChemMedChem 6:1107–1118. https://doi.org/10.1002/cmdc.201100054

    Article  CAS  PubMed  Google Scholar 

  98. Kaska WC, Carrano C, Michalowski J, Jackson J, Levinson W (1978) Inhibition of the RNA dependent DNA polymerase and the malignant transforming ability of Rous sarcoma virus by thiosemicarbazone-transition metal complexes. Bioinorg Chem 3:245–254. https://doi.org/10.1016/S0006-3061(00)80198-2

    Article  Google Scholar 

  99. Bacher F, Enyedy EA, Nagy NV, Rockenbauer A, Bognár GM, Trondl R, Novak MS, Klapproth E, Kiss T, Arion VB (2013) Copper(II) complexes with highly water-soluble L- and D-proline–thiosemicarbazone conjugates as potential inhibitors of topoisomerase IIα. Inorg Chem 52:8895–8908. https://doi.org/10.1021/ic401079w

    Article  CAS  PubMed  Google Scholar 

  100. Bisceglie F, Pinelli S, Alinovi R, Goldoni M, Mutti A, Camerini A, Piola L, Tarasconi P, Pelosi G (2014) Cinnamaldehyde and cuminaldehyde thiosemicarbazones and their copper(II) and nickel(II) complexes: a study to understand their biological activity. J Inorg Biochem 140:111–125. https://doi.org/10.1016/j.jinorgbio.2014.07.014

    Article  CAS  PubMed  Google Scholar 

  101. Bisceglie F, Musiari A, Pinelli S, Alinovi R, Menozzi I, Polverini E, Tarasconi P, Tavone M, Pelosi G (2015) Quinoline-2-carboxaldehyde thiosemicarbazones and their Cu(II) and Ni(II) complexes as topoisomerase IIa inhibitors. J Inorg Biochem 152:10–19. https://doi.org/10.1016/j.jinorgbio.2015.08.008

    Article  CAS  PubMed  Google Scholar 

  102. Djoko KY, Paterson BM, Donnelly PS, McEwan AG (2014) Antimicrobial effects of copper(II) bis(thiosemicarbazonato) complexes provide new insight into their biochemical mode of action. Metallomics 6:854–863. https://doi.org/10.1039/c3mt00348e

    Article  CAS  PubMed  Google Scholar 

  103. Moore EC, Zedeck MS, Agrawal KC, Sartorelli AC (1970) Inhibition of ribonucleoside diphosphate reductase by 1-formylisoquinoline thiosemicarbazone and related compounds. Biochemistry 9:4492–4498. https://doi.org/10.1021/bi00825a005

    Article  CAS  PubMed  Google Scholar 

  104. Moore EC, Booth BA, Sartorelli AC (1971) Inhibition of deoxyribonucleotide synthesis by pyridine carboxaldehyde thiosemicarbazones. Cancer Res 31:235–238

    CAS  PubMed  Google Scholar 

  105. Sartorelli AC, Agrawal KC, Moore EC (1971) Mechanism of inhibition of ribonucleoside diphosphate reductase by alpha-(N)-heterocycliccarboxaldehyde thiosemicarbazones. Biochem Pharmacol 20:3119–3123. https://doi.org/10.1016/0006-2952(71)90116-X

    Article  CAS  PubMed  Google Scholar 

  106. Thelander L, Gräslund A (1983) Mechanism of inhibition of mammalian ribonucleotide reductase by the iron chelate of 1-formylisoquinoline thiosemicarbazone. Destruction of the tyrosine free radical of the enzyme in an oxygen-requiring reaction. J Biol Chem 258:4063–4066. https://doi.org/10.1016/S0021-9258(18)32582-1

    Article  CAS  PubMed  Google Scholar 

  107. Shao J, Zhou B, Di Bilio AJ, Zhu L, Wang T, Qi C, Shih J, Yen Y (2006) A Ferrous-Triapine® complex mediates formation of reactive oxygen species that inactivate human ribonucleotide reductase. Mol Cancer Ther 5:586–592. https://doi.org/10.1158/1535-7163.MCT-05-0384

    Article  CAS  PubMed  Google Scholar 

  108. Popović-Bijelić A, Kowol CR, Lind MES, Luo J, Himo F, Enyedy ÉA, Arion VB, Gräslund A (2011) Ribonucleotide reductase inhibition by metal complexes of Triapine® (3-aminopyridine-2-carboxaldehyde thiosemicarbazone): a combined experimental and theoretical study. J Inorg Biochem 105:1422–1431. https://doi.org/10.1016/j.jinorgbio.2011.07.003

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  109. Akladios FN, Andrew SD, Parkinson CJ (2015) Selective induction of oxidative stress in cancer cells via synergistic combinations of agents targeting redox homeostasis. Bioorganic Med Chem 23:3097–3104. https://doi.org/10.1016/j.bmc.2015.05.006

    Article  CAS  Google Scholar 

  110. Kalinowski DS, Stefani C, Toyokuni S, Ganz T, Anderson GJ, Subramaniam NV, Trinder D, Olynyk JK, Chua A, Jansson PJ, Sahni S, Lane DJR, Merlot AM, Kovacevic Z, Huang MLH, Lee CS, Richardson DR (2016) Redox cycling metals: pedaling their roles in metabolism and their use in the development of novel therapeutics. Biochim Biophys Acta-Mol Cell Res 1863:727–748. https://doi.org/10.1016/j.bbamcr.2016.01.026

    Article  CAS  Google Scholar 

  111. Akladios FN, Andrew SD, Parkinson CJ (2016) Increased generation of intracellular reactive oxygen species initiates selective cytotoxicity against the MCF-7 cell line resultant from redox active combination therapy using copper–thiosemicarbazone complexes. J Biol Inorg Chem 21:407–419. https://doi.org/10.1007/s00775-016-1350-2

    Article  CAS  PubMed  Google Scholar 

  112. Whitnall M, Howard J, Ponka P, Richardson DR (2006) A class of iron chelators with a wide spectrum of potent antitumor activity that overcomes resistance to chemotherapeutics. Proc Natl Acad Sci 103:14901–14906. https://doi.org/10.1073/pnas.0604979103

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  113. Kolesar JM, Sachidanandam K, Schelman WR, Eickhoff J, Holen KD, Traynor AM, Alberti DB, Thomas JP, Chitambar CR, Wilding G, Antholine WE (2011) Cytotoxic evaluation of 3-aminopyridine-2-carboxaldehyde thiosemicarbazone in peripheral blood lymphocytes of patients with refractory solid tumors using electron paramagnetic resonance. Exp Ther Med 2:119–123. https://doi.org/10.3892/etm.2010.165

    Article  CAS  PubMed  Google Scholar 

  114. Lovejoy DB, Jansson PJ, Brunk UT, Wong J, Ponka P, Richardson DR (2011) Antitumor activity of metal-chelating compound Dp44mT is mediated by formation of a redox-active copper complex that accumulates in lysosomes. Cancer Res 71:5871–5880. https://doi.org/10.1158/0008-5472.CAN-11-1218

    Article  CAS  PubMed  Google Scholar 

  115. Ishiguro K, Lin ZP, Penketh PG, Shyam K, Zhu R, Baumann RP, Zhu YL, Sartorelli AC, Rutherford TJ, Ratner ES (2014) Distinct mechanisms of cell-kill by triapine, and its terminally dimethylated derivative Dp44mT due to a loss or gain of activity of their copper(II) complexes. Biochem Pharmacol 91:312–322. https://doi.org/10.1016/j.bcp.2014.08.006

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  116. Haeili M, Moore C, Davis CJC, Cochran JB, Shah S, Shrestha TB, Zhang Y, Bossmann SH, Benjamin WH, Kutsch O, Wolschendorf F (2014) Copper complexation screen reveals compounds with potent antibiotic properties against methicillin-resistant Staphylococcus aureus. Antimicrob Agents Ch 58:3727–3736. https://doi.org/10.1128/aac.02316-13

    Article  Google Scholar 

  117. Stacy AE, Palanimuthu D, Bernhardt PV, Kalinowski DS, Jansson PJ, Richardson DR (2016) Zinc(II)-thiosemicarbazone complexes are localized to the lysosomal compartment where they transmetallate with copper ions to induce cytotoxicity. J Med Chem 59:4965–4984. https://doi.org/10.1021/acs.jmedchem.6b00238

    Article  CAS  PubMed  Google Scholar 

  118. Jansson PJ, Sharpe PC, Bernhardt PV, Richardson DR (2010) Novel thiosemicarbazones of the ApT and DpT series and their copper complexes: identification of pronounced redox activity and characterization of their antitumor activity. J Med Chem 53:5759–5769. https://doi.org/10.1021/jm100561b

    Article  CAS  PubMed  Google Scholar 

  119. French FA, Blanz EJ, Shaddix SC, Brockman RW (1974) α-(N)-Formylheteroaromatic thiosemicarbazones. inhibition of tumor-derived ribonucleoside diphosphate reductase and correlation with in vivo antitumor activity. J Med Chem 17:172–181. https://doi.org/10.1021/jm00248a006

    Article  CAS  PubMed  Google Scholar 

  120. Lovejoy DL, Richardson DR (2002) Novel “hybrid” iron chelators derived from aroylhydrazones and thiosemicarbazones demonstrate selective antiproliferative activity against tumor cells. Blood 100:666–675. https://doi.org/10.1182/blood.V100.2.666

    Article  CAS  PubMed  Google Scholar 

  121. Bacher F, Dömötör O, Kaltenbrunner M, Mojović M, Popović-Bijelić A, Gräslund A, Ozarowski A, Filipovico L, Radulovićo S, Enyedy ÉA, Arion VA (2014) Effects of terminal dimethylation and metal coordination of proline-2-formylpyridine thiosemicarbazone hybrids on lipophilicity, antiproliferative activity, and hR2 RNR inhibition. Inorg Chem 53:12595–12609. https://doi.org/10.1021/ic502239u

    Article  CAS  PubMed  Google Scholar 

  122. Stefani C, Punnia-Moorthy G, Lovejoy DB, Jansson PJ, Kalinowski DS, Sharpe PC, Bernhardt PV, Richarrdson DR (2011) Halogenated 2′-benzoylpyridine thiosemicarbazone (XBpT) chelators with potent and selective anti-neoplastic activity: relationship to intracellular redox activity. J Med Chem 54:6936–6948. https://doi.org/10.1021/jm200924c

    Article  CAS  PubMed  Google Scholar 

  123. Wang L, He W, Yu Z (2013) Transition-metal mediated carbon–sulfur bond activation and transformations. Chem Soc Rev 42:599–621. https://doi.org/10.1039/C2CS35323G

    Article  CAS  PubMed  Google Scholar 

  124. Ren P, Pike SD, Pernik I, Weller AS, Willis MC (2015) Rh–POP pincer xantphos complexes for C-S and C–H activation. Implications for carbothiolation catalysis. Organometallics 34:711–723. https://doi.org/10.1021/om500984y

    Article  CAS  Google Scholar 

  125. Munjanja L, Brennessel WW, Jones WD (2015) Room-temperature carbon–sulfur bond activation by a reactive (dippe)Pd fragment. Organometallics 34:1716–1724. https://doi.org/10.1021/acs.organomet.5b00194

    Article  CAS  Google Scholar 

  126. Li Y, Rauchfuss TB (2016) Synthesis of diiron(I) dithiolato carbonyl complexes. Chem Rev 116:7043–7077. https://doi.org/10.1021/acs.chemrev.5b00669

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  127. Kumar S, Guyon F, Knorr M, Labat S, Miqueu K, Golz C, Strohmann C (2017) Experimental and theoretical studies on the mechanism of the C–S bond activation of PdII thiolate/thioether complexes. Organometallics 36:1303–1321. https://doi.org/10.1021/acs.organomet.7b00039

    Article  CAS  Google Scholar 

  128. Lou J, Wang Q, Wu P, Wang H, Zhou YG, Yu Z (2020) Transition-metal mediated carbon–sulfur bond activation and transformations: an update. Chem Soc Rev 49:4307–4359. https://doi.org/10.1039/C9CS00837C

    Article  CAS  Google Scholar 

  129. Gómez-Saiz P, Gil-García R, Maestro MA, Pizarro JL, Arriortua MI, Lezama L, Rojo T, García Tojal J (2005) Unexpected behaviour of pyridine-2-carbaldehyde thiosemicarbazonatocopper(II) entities in aqueous basic medium-partial transformation of thioamide into nitrile. Eur J Inorg Chem 3409–3413. https://doi.org/10.1002/ejic.200500326

  130. García-Tojal J, Urtiaga MK, Cortés R, Lezama L, Arriortua MI, Rojo T (1994) Synthesis, structure, spectroscopic and magnetic properties of two copper(II) dimers containing pyridine-2-carbaldehyde thiosemicarbazonate (L), [{CuL(X)}2] (X = Cl or Br). J Chem Soc Dalton Trans 2233–2238. https://doi.org/10.1039/DT9940002233

  131. García-Tojal J, Gil-García R, Fouz VI, Madariaga G, Lezama L, Galletero MS, Borrás J, Nollmann FI, García-Girón C, Alcaraz R, Cavia-Saiz M, Muñiz P, Palacios Ò, Samper KG, Rojo T (2018) Revisiting the thiosemicarbazonecopper(II) reaction with glutathione. Activity against colorectal carcinoma cell lines. J Inorg Biochem 180:69–79. https://doi.org/10.1016/j.jinorgbio.2017.12.005

    Article  CAS  PubMed  Google Scholar 

  132. Gil-García R, Fraile R, Donnadieu B, Madariaga G, Januskaitis V, Rovira J, González L, Borrás J, Arnáiz FJ, García-Tojal J (2013) Desulfurization processes of thiosemicarbazonecopper(II) derivatives in acidic and basic aqueous media. New J Chem 37:3568–3580. https://doi.org/10.1039/C3NJ00321C

    Article  Google Scholar 

  133. Ainscough EW, Brodie AM, Denny WA, Finlay GJ, Ranford JD (1998) Nitrogen, sulfur and oxygen donor adducts with copper(II) complexes of antitumor 2-formylpyridinethiosemicarbazone analogs: physicochemical and cytotoxic studies. J Inorg Biochem 70:175–185. https://doi.org/10.1016/S0162-0134(98)10011-9

    Article  CAS  PubMed  Google Scholar 

  134. Gil-García R, Madariaga G, Jiménez-Pérez A, Herrán-Torres I, Gago-González A, Ugalde M, Januskaitis V, Barrera-García J, Insausti M, Galletero MS, Borrás J, Cuevas JV, Pedrido R, Gómez-Saiz P, Lezama L, García-Tojal J (2023) Perchlorate-induced structural diversity in thiosemicarbazone-copper(II) complexes provides insights to understand the reactivity in acid and basic media. CrystEngComm 25:2213–2226. https://doi.org/10.1039/D3CE00119A

    Article  Google Scholar 

  135. Wang YT, Fang Y, Zhao M, Li MX, Ji YM, Han QX (2017) Cu(II), Ga(III) and In(III) complexes of 2-acetylpyridine N(4)-phenylthiosemicarbazone: synthesis, spectral characterization and biological activities. MedChemComm 8:2125–2132. https://doi.org/10.1039/C7MD00415J

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  136. Al-Eisawi Z, Stefani C, Jansson PJ, Arvind A, Sharpe PC, Basha MT, Iskander GM, Kumar N, Kovacevic Z, Lane DJR, Sahni S, Bernhardt PV, Richardson DR, Kalinowski DS (2016) Novel mechanism of cytotoxicity for the selective selenosemicarbazone, 2-acetylpyridine 4,4-dimethyl-3-selenosemicarbazone (Ap44mSe): lysosomal membrane permeabilization. J Med Chem 59:294–312. https://doi.org/10.1021/acs.jmedchem.5b01399

    Article  CAS  PubMed  Google Scholar 

  137. Enyedy ÉA, Nagy NV, Zsigó É, Kowol CR, Arion VB, Keppler BK, Kiss T (2010) Comparative solution equilibrium study of the interactions of copper(II), iron(II) and zinc(II) with triapine® (3-aminopyridine-2-carbaldehyde thiosemicarbazone) and related ligands. Eur J Inorg Chem 2010:1717–1728. https://doi.org/10.1002/ejic.200901174

    Article  CAS  Google Scholar 

  138. Dömötör O, May NV, Pelivan K, Kiss T, Keppler BK, Kowol CR, Enyedy EA (2018) A comparative study of α-N-pyridyl thiosemicarbazones: spectroscopic properties, solution stability and copper(II) complexation. Inorg Chim Acta 472:264–275. https://doi.org/10.1016/j.ica.2017.07.001

    Article  CAS  Google Scholar 

  139. Gil-García R, Gómez-Saiz P, Díez-Gómez V, Madariaga G, Insausti M, Lezama L, Cuevas JV, García-Tojal J (2014) Thiosemicarbazonecopper(II) compounds with halide/hexafluorosilicate anions: structure, water clusters, non-covalent interactions and magnetism. Polyhedron 81:675–686. https://doi.org/10.1016/j.poly.2014.07.032

    Article  CAS  Google Scholar 

  140. Abras A, Beraldo H, Fantini EO, Borges RHU, Da Rocha MA, Tosi L (1990) Spectroscopic studies of metal complexes containing π-delocalized sulfur ligands. Mössbauer and kinetic studies of iron(II) and iron(III) complexes of the antitumor agent 2-formylpyridine thiosemicarbazone. Inorg Chim Acta 172:113–117. https://doi.org/10.1016/S0020-1693(00)80459-4

    Article  CAS  Google Scholar 

  141. Borges RHU, Paniago E, Beraldo H (1997) Equilibrium and kinetic studies of iron(II) and iron(III) complexes of some α(N)-heterocyclic thiosemicarbazones. Reduction of the iron(III) complexes of 2-formylpyridine thiosemicarbazone and 2-acetylpyridine thiosemicarbazone by cellular thiol-like reducing agents. J Inorg Biochem 65:267–275. https://doi.org/10.1016/S0162-0134(96)00142-0

    Article  CAS  PubMed  Google Scholar 

  142. García-Tojal J, Donnadieu B, Costes JP, Serra JL, Lezama L, Rojo T (2002) Spectroscopic properties of iron thiosemicarbazone compounds. Structure of [Fe(C7H7N4S)2]·1.25H2O. Inorg Chim Acta 333:132–137. https://doi.org/10.1016/S0020-1693(02)00802-2

    Article  Google Scholar 

  143. Fukumoto K, Sakai A, Hayasaka K, Nakazawa H (2013) Desulfurization and H-migration of secondary thioamides catalyzed by an iron complex to yield imines and their reaction mechanism. Organometallics 32:2889–2892. https://doi.org/10.1021/om400304v

    Article  CAS  Google Scholar 

  144. Mutoh Y, Sakigawara M, Niiyama I, Saito S, Ishii Y (2014) Synthesis of rhodium−primary thioamide complexes and their desulfurization leading to rhodium sulfido cubane-type clusters and nitriles. Organometallics 33:5414–5422. https://doi.org/10.1021/om500714c

    Article  CAS  Google Scholar 

  145. Guo W, Liu G, Deng L, Mei W, Zou X, Zhong Y, Zhou X, Fan X, Zheng L (2021) Metal- and oxidant-free green three-component desulfurization and deamination condensation approach to fully substituted 1 H-1,2,4-triazol-3-amines and their photophysical properties. J Org Chem 86:17986–18003. https://doi.org/10.1021/acs.joc.1c02313

    Article  CAS  PubMed  Google Scholar 

  146. Gómez-Saiz P, García-Tojal J, Diez-Gómez V, Gil-García R, Pizarro JL, Arriortua MI, Rojo T (2005) Indirect evidences of desulfurization of a thiosemicarbazonecopper(II) system in aqueous basic medium. Inorg Chem Commun 8:259–262. https://doi.org/10.1016/j.inoche.2004.12.016

    Article  CAS  Google Scholar 

  147. Castiñeiras A, Garcia-Santos I (2008) Desulfuration and cyclization of (Z)-2-[amino(pyridine-2-yl)methylene]- hydrazonecarbothioamide in the presence of manganese(II). Zeitschrift fur Anorg und Allg Chemie 634:2907–2916. https://doi.org/10.1002/zaac.200800326

    Article  CAS  Google Scholar 

  148. Van Poppel LH, Groy TL, Caudle MT (2004) Carbon-Sulfur bond cleavage in bis(N-alkyldithiocarbamato)cadmium(II) complexes: heterolytic desulfurization coupled to topochemical proton transfer. Inorg Chem 43:3180–3188. https://doi.org/10.1021/ic035135v

    Article  CAS  PubMed  Google Scholar 

  149. Al-Mutairi AA, Al-Alshaikh MA, Al-Omary FAM, Hassan HM, El-Mahdy AM, El-Emam AA (2019) Synthesis, antimicrobial, and anti-proliferative activities of novel 4-(adamantan-1-yl)-1-arylidene-3- thiosemicarbazides, 4-arylmethyl N-(adamantan-1-yl) piperidine-1-carbothioimidates, and related derivatives. Molecules 24:4308. https://doi.org/10.3390/molecules24234308

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  150. Jeong H, Kang Y, Kim J, Kim BK, Hong S (2019) Factors that determine thione(thiol)-disulfide interconversion in a bis(thiosemicarbazone) copper(II) complex. RSC Adv 9:9049–9052. https://doi.org/10.1039/c9ra01115c

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  151. Pedrido R, Romero MJ, Bermejo MR, González-Noya AM, García-Lema I, Zaragoza G (2008) Metal-catalysed oxidation processes in thiosemicarbazones: new complexes with the ligand N-{2-([4-N-ethylthiosemicarbazone]-methyl)phenyl}-p- toluenesulfonamide. Chem Eur J 14:500–512. https://doi.org/10.1002/chem.200700867

    Article  CAS  PubMed  Google Scholar 

  152. Pedrido R, Romero MJ, Bermejo MR, Martínez-Calvo M, González-Noya AM, Zaragoza G (2009) Coordinative trends of a tridentate thiosemicarbazone ligand: synthesis, characterization, luminescence studies and desulfurization processes. Dalton Trans 39:8329–8340. https://doi.org/10.1039/b908782f

    Article  CAS  Google Scholar 

  153. Da Rosa Justim J, Correa Bohs LM, Barreto Martins B, Tribuzy Bandeira KC, Lopes de Melo AP, Carratu Gervini V, Bresolin L, Godoi M, de Menezes Peixoto CR (2021) Electrochemical characterization of isatin-thiosemicarbazone derivatives. J Chem Sci 133:124. https://doi.org/10.1007/s12039-021-01970-x

    Article  CAS  Google Scholar 

  154. Pelivan K, Frensemeier LM, Karst U et al (2018) Comparison of metabolic pathways of different α-N-heterocyclic thiosemicarbazones. Anal Bioanal Chem 410:2343–2361. https://doi.org/10.1007/s00216-018-0889-x

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  155. Gómez-Saiz P, García-Tojal J, Maestro MA, Arnaiz FJ, Rojo T (2002) Evidence of desulfurization in the oxidative cyclization of thiosemicarbazones. Conversion to 1,3,4-oxadiazole derivatives. Inorg Chem 41:1345–1347. https://doi.org/10.1021/ic015625s

    Article  CAS  PubMed  Google Scholar 

  156. Gómez-Saiz P, García-Tojal J, Maestro MA, Mahía J, Arnaiz FJ, Lezama L, Rojo T (2003) New 1,3,4-oxadiazolecopper(II) derivatives obtained from thiosemicarbazone complexes. Eur J Inorg Chem 2003:2639–2650. https://doi.org/10.1002/ejic.200200689

    Article  CAS  Google Scholar 

  157. Hiremath SP, Goudar NN, Purohit MG (1981) Synthesis of substituted 1′,3′,4′-oxadiazolyl-indoles, thiadiazolyl-indoles and triazolyl-indoles. Indian J Chem Sect B 20:388–390

    Google Scholar 

  158. Hiremath SP, Biradar JS, Kudari SM (1984) Synthesis of substituted oxadiazoles, thiadiazoles and triazoles and evaluation of their biological activity. J Indian Chem Soc 61:74–76. https://doi.org/10.5281/zenodo.6325527

    Article  CAS  Google Scholar 

  159. Fernandes PS, Sonar TM (1986) Synthesis and biological activity of heterocyclic derivatives derived from ethyl-2-hydroxyquinoxaline-3-carboxylate. J Indian Chem Soc 63:427–429. https://doi.org/10.5281/zenodo.6273852

    Article  CAS  Google Scholar 

  160. Hiremath SP, Sonar VN, Sekhar KR, Purohit MG (1989) Synthesis of substituted oxadiazolylindoles, thiadiazolylindoles and indolylthiazolidinones. Indian J Chem Sect B 28B:626–630

    CAS  Google Scholar 

  161. Raman K, Singh HK, Salzman SK, Parmar SS (1993) Substituted thiosemicarbazides and corresponding cyclized 1,3,4-oxadiazoles and their antiinflammatory activity. J Pharm Sci 82:167–169. https://doi.org/10.1002/jps.2600820210

    Article  CAS  PubMed  Google Scholar 

  162. Kelarev VI, Karakhanov RA, Gassanov SS, Morozova GV, Kuatbekova KP (1993) Synthesis of 1,3,4-oxa(thia)diazole and 1,2,4-triazolederivatives containing 3-indolylmethyl radicals. Russ J Org Chem 29:388–395

    CAS  Google Scholar 

  163. Albar HA, Makki MSI, Faidallah HM (1996) Synthesis of heterocyclic compounds from delta-unsaturated 1,3-diketo-esters. Indian J Chem Sect B 35:23–29

    Google Scholar 

  164. Vashi BS, Mehta DS, Shah VH (1996) Synthesis of 2,5-disubstituted-1,3,4-oxadiazole, 1,5-disubstituted-2-mercapto-1,3,4-triazole and 2,5-disubstituted-1,3,4-thiadiazole derivatives as potential antimicrobial agents. Indian J Chem Sect B 35:111–115. https://doi.org/10.1002/chin.199617050

    Article  Google Scholar 

  165. Rao GR, Mogilaiah K, Sreenivasulu B (1996) Synthesis and antimicrobial activity of 1′,2′,4′-triazolyl/1′,3′,4′-thiadiazolyl/1′,3′,4′-oxadiazolyl-1,8-naphthyridines and related compounds. Indian J Chem Sect B 35:339–344

    Google Scholar 

  166. Omar FA, Mahfouz NM, Rahman MA (1996) Design, synthesis and antiinflammatory activity of some 1,3,4-oxadiazole derivatives. Eur J Med Chem 31:819–825. https://doi.org/10.1016/0223-5234(96)83976-6

    Article  CAS  PubMed  Google Scholar 

  167. Tripathi P, Pal A, Jancik V, Pandey AK, Singh J, Singh NK (2007) Metal-assisted transformation of N-benzoyldithiocarbazate to 5-phenyl-1,3,4-oxadiazole-2-thiol in the presence of ethylenediamine, and its first row transition metalcomplexes. Polyhedron 26:2597–2602. https://doi.org/10.1016/j.poly.2006.12.046

    Article  CAS  Google Scholar 

  168. Hassan AA, Mourad AFE, Abou-Zied AH (2007) Reaction of 1-acylthiosemicarbazides with ethenetetracarbonitrile. J Heterocycl Chem 44:1171–1176. https://doi.org/10.1002/jhet.5570440532

    Article  CAS  Google Scholar 

  169. Hassan AA, Mourad AE, Abuo-Zied AH (2007) Benzo- and naphthoimidazoxadiazolediene, naphthobisthiazole as well as naphthothiazine derivatives from 1-acylthiosemicarbazides. ARKIVOC 222–235. https://doi.org/10.3998/ark.5550190.0008.124

  170. Mekuskiene G, Tumkevicius S, Vainilavicius P (2002) 5-(4,6-diphenyl-2-pyrimidinyl)-1,3,4-oxa(thia)diazoles and 1,2,4-triazoles. J Chem Res. https://doi.org/10.3184/030823402103171898

    Article  Google Scholar 

  171. Dolman SJ, Gosselin F, O’Shea PD, Davies IW (2006) Superior reactivity of thiosemicarbazides in the synthesis of 2-amino-1,3,4-oxadiazoles. J Org Chem 71:9548–9551. https://doi.org/10.1021/jo0618730

    Article  CAS  PubMed  Google Scholar 

  172. Singh NK, Bharty MK, Dulare R, Butcher RJ (2009) Synthesis and X-ray crystallographic studies of Ni(II) and Cu(II) complexes of [5-(4-pyridyl)-1,3,4] oxadiazole-2-thione/thiol formed by transformation of N-(pyridine-4-carbonyl)-hydrazine carbodithioate in the presence of ethylenediamine. Polyhedron 28:2443–2449. https://doi.org/10.1016/j.poly.2009.04.030

    Article  CAS  Google Scholar 

  173. Li Z, Zhu A, Yang J (2012) One-pot three-component mild synthesis of 2-aryl-3-(9-alkylcarbazol-3-yl)thiazolin-4-ones. J Heterocycl Chem 49:1458–1461. https://doi.org/10.1002/jhet.1047

    Article  CAS  Google Scholar 

  174. Bharti A, Bharty MK, Kashyap S, Singh UP, Butcher RJ, Singh NK (2013) Hg(II) complexes of 4-phenyl-5-(3-pyridyl)-1,2,4-triazole-3-thione and 5-(4-pyridyl)-1,3,4-oxadiazole-2-thione and a Ni(II) complex of 5-(thiophen-2-yl)-1,3,4-oxadiazole-2-thione: synthesis and X-ray structural studies. Polyhedron 50:582–591. https://doi.org/10.1016/j.poly.2012.11.043

    Article  CAS  Google Scholar 

  175. Yang Z, She M, Yin B, Hao L, Obst M, Li J (2015) Solvent-dependent turn-on probe for dual monitoring of Ag+ and Zn2+ in living biological samples. Anal Chim Acta 868:53–59. https://doi.org/10.1016/j.aca.2015.01.052

    Article  CAS  PubMed  Google Scholar 

  176. Bao W, Chen C, Yi N, Jiang J, Zeng Z, Deng W, Peng Z, Xiang J (2017) Synthesis of 2-amino-1,3,4-oxadiazoles through elemental sulfur promoted cyclization of hydrazides with isocyanides. Chin J Chem 35:1611–1618. https://doi.org/10.1002/cjoc.201700188

    Article  CAS  Google Scholar 

  177. Golmohammadi F, Balalaie S, Hamdan F, Maghari S (2018) Efficient synthesis of novel conjugated 1,3,4-oxadiazole-peptides. New J Chem 42:4344–4351. https://doi.org/10.1039/c7nj04720g

    Article  CAS  Google Scholar 

  178. Abu-Hashem AA (2021) Synthesis and antimicrobial activity of new 1,2,4-triazole, 1,3,4-oxadiazole, 1,3,4-thiadiazole, thiopyrane, thiazolidinone, and azepine derivatives. J Heterocycl Chem 58:74–92. https://doi.org/10.1002/jhet.4149

    Article  CAS  Google Scholar 

  179. Landquist JK (1970) Oxidative cyclisation of ketone thiosemicarbazones. Part I. 4-methyl- and 4-aryl-thiosemicarbazones. J Chem Soc C 63–66. https://doi.org/10.1039/J39700000063

  180. Xiao S, Lee W, Chen F, Zavalij PY, Gutierrez O, Davis JT (2020) Oxidation of 8-thioguanosine gives redox-responsive hydrogels and reveals intermediates in a desulfurization pathway. Chem Commun 56:6981–6984. https://doi.org/10.1039/D0CC02926B

    Article  CAS  Google Scholar 

  181. Baird IR, Cameron BR, Skerlj RT (2003) Unique chemistry of amino acid dithiocarbamates with Ru(III) bis-β-diketonates. Inorg Chim Acta 353:107–118. https://doi.org/10.1016/S0020-1693(03)00233-0

    Article  CAS  Google Scholar 

  182. Ng S, Ziller JW, Farmer PJ (2004) Multiple pathways for the oxygenation of a ruthenium(II) dithiocarbamate complex: S-oxygenation and S-extrusion. Inorg Chem 43:8301–8309. https://doi.org/10.1021/ic048661a

    Article  CAS  PubMed  Google Scholar 

  183. Fernández-Fariña S, González-Barcia LM, Romero MJ, García-Tojal J, Maneiro M, Seco JM, Zaragoza G, Martínez-Calvo M, González-Noya AM, Pedrido R (2022) Conversion of a double-tetranuclear cluster silver helicate into a dihelicate via a rare desulfurization process. Inorg Chem Front 9:531–536. https://doi.org/10.1039/d1qi01308d

    Article  CAS  Google Scholar 

  184. Alsop L, Cowley AR, Dilworth JR, Donnelly PS, Peach JM, Rider JT (2005) Investigations into some aryl substituted bis(thiosemicarbazones) and their copper complexes. Inorg Chim Acta 358:2770–2780. https://doi.org/10.1016/j.ica.2005.03.027

    Article  CAS  Google Scholar 

  185. Gooneh-Farahani S, Anbia M (2023) A review of advanced methods for ultra-deep desulfurization under mild conditions and the absence of hydrogen. J Environ Chem Eng 11:108997. https://doi.org/10.1016/j.jece.2022.108997

    Article  CAS  Google Scholar 

  186. Aly AA, Hassan AA, Brown AB, Ibrahim MAA, AbdAl-Latif ESSM (2017) Azines from one-pot reaction of thiosemicarbazones. J Sulphur Chem 38:11–17. https://doi.org/10.1080/17415993.2016.1210146

    Article  CAS  Google Scholar 

  187. Kassim K, Hamali MA, Yamin B (2019) A New alternative synthesis of salicylaldazine via microwave irradiation method. J Chem 2019:9546373. https://doi.org/10.1155/2019/9546373

    Article  CAS  Google Scholar 

  188. Qiu W, Shi S, Li R, Lin X, Rao L, Sun Z (2021) A mild, general, metal-free method for desulfurization of thiols and disulfides induced by visible-light. Chin J Chem 39:1255–1258. https://doi.org/10.1002/cjoc.202000607

    Article  CAS  Google Scholar 

  189. Maji M, Chatterjee M, Ghosh S, Chattopadhyay SK, Wu BM, Mak TCW (1999) Chemistry of ruthenium(II) complexes of the tridentate NNS donor methyl 2-pyridyl ketone 4-(4-tolyl)thiosemicarbazone. Isolation and structural characterisation of a novel ruthenium(II) complex containing a co-ordinated imine of an alpha-N heterocyclic ketone. J Chem Soc Dalton Trans 135–140. https://doi.org/10.1039/A806341I

  190. Hassan AA, El-Sheref EM (2010) Chemistry and heterocyclization of dithiobiurea and thioureidoalkylthiourea. J Heterocycl Chem 47:764–784. https://doi.org/10.1002/jhet.406

    Article  CAS  Google Scholar 

  191. Da S, Maia PI, Nguyen HH, Ponader D, Hagenbach A, Bergemann S, Gust R, Deflon VM, Abram U (2012) Neutral gold complexes with tridentate SNS thiosemicarbazide ligands. Inorg Chem 51:1604–1613. https://doi.org/10.1021/ic201905t

    Article  CAS  Google Scholar 

  192. Gil-García R, Zichner R, Díez-Gómez V, Donnadieu B, Madariaga G, Insausti M, Lezama L, Vitoria P, Pedrosa MR, García-Tojal J (2010) Polyoxometallate-thiosemicarbazone hybrid compounds. Eur J Inorg Chem 2010:4513–4525. https://doi.org/10.1002/ejic.201000484

    Article  CAS  Google Scholar 

  193. Cowley AR, Dilworth JR, Donnelly PS, Woollard-Shore J (2003) Synthesis and characterisation of new homoleptic rhenium thiosemicarbazone complexes. J Chem Soc Dalton Trans 3:748–754. https://doi.org/10.1039/B210540N

    Article  Google Scholar 

  194. Matesanz AI, Pastor C, Souza P (2007) Synthesis and structural characterization of a disulphide-bridged tetranuclear palladium(II) complex derived from 3,5-diacetyl 1,2,4-triazole bis(4-ethylthiosemicarbazone). Inorg Chem Commun 10:97–100. https://doi.org/10.1016/j.inoche.2006.09.016

    Article  CAS  Google Scholar 

  195. Zhao Y, Lin Z, He C, Wu H, Duan C (2006) A “turn-on” fluorescent sensor for selective Hg(II) detection in aqueous media based on metal-induced dye formation. Inorg Chem 45:10013–10015. https://doi.org/10.1021/ic061067b

    Article  CAS  PubMed  Google Scholar 

  196. Zhang P, Shi B, Zhang Y, Lin Q, Yao H, You XM, Wei TB (2013) A selective fluorogenic chemodosimeter for Hg2+ based on the dimerization of desulfurized product. Tetrahedron 69:10292–10298. https://doi.org/10.1016/j.tet.2013.10.024

    Article  CAS  Google Scholar 

  197. Hwang KS, Park KY, Bin KD, Chang SK (2017) Fluorescence sensing of Ag+ ions by desulfurization of an acetylthiourea derivative of 2-(2-hydroxyphenyl)benzothiazole. Dyes Pigm 147:413–419. https://doi.org/10.1016/j.dyepig.2017.08.041

    Article  CAS  Google Scholar 

  198. Bulak E, Dogan I, Varnali T, Schwederski B, Gunal SE, Lönnecke P, Bubrin M, Kaim W (2021) An acyclic diaminocarbene complex of platinum formed by desulfurization of 1,3-bis(3-methylpyridin-2-yl)thiourea. Eur J Inorg Chem 2:2425–2432. https://doi.org/10.1002/ejic.202100277

    Article  CAS  Google Scholar 

  199. Singh S, Chaturvedi J, Bhattacharya S (2012) Studies of synthesis, structural features of Cu(I) thiophene-2-thiocarboxylates and unprecedented desulfurization of Cu(II) thiocarboxylate complexes. Dalton Trans 41:424–431. https://doi.org/10.1039/C1DT10629E

    Article  CAS  PubMed  Google Scholar 

  200. Bigoli F, Deplano P, Mercuri L, Pellinghelli MA, Pintus G, Trogu EF (1999) Unusual desulfurization of a nickel dithiolene by bis(2-diphenylphosphinophenyl)phenylphosphine (tp) to produce Ni(tp)(R4btimdt) [R4btimdt = 5,5′-bis(1,3-dialkyl-4-imidazolidine-2-thione-4-thiolate], the first complex of this class of ligands. Chem Commun 698:2093–2094

    Article  Google Scholar 

  201. Chawla SK, Arora M, Nättinen K, Rissanen K (2006) Unique copper ion catalyzed hydrolytic cleavage of C-N(2) bond of thiosemicarbazide. Polyhedron 25:627–634. https://doi.org/10.1016/j.poly.2005.05.021

    Article  CAS  Google Scholar 

  202. Voitekhovich SV, Lyakhov AS, Ivashkevich LS, Ivashkevich OA (2020) Copper-assisted desulfurization of 1-R-tetrazole-5-thiols under complexation. Inorg Chem Commun 114:107827–107830. https://doi.org/10.1016/j.inoche.2020.107827

    Article  CAS  Google Scholar 

  203. Tardito S, Bussolati O, Maffini M, Tegoni M, Giannetto M, Dall’Asta V, Franchi-Gazzola R, Lanfranchi M, Pellinghelli MA, Mucchino C, Mori G, Marchiò L (2007) Thioamido coordination in a thioxo-1,2,4-triazole copper(II) complex enhances nonapoptotic programmed cell death associated with copper accumulation and oxidative stress in human cancer cells. J Med Chem 50:1916–1924. https://doi.org/10.1021/jm061174f

    Article  CAS  PubMed  Google Scholar 

  204. Madshus IH (1988) Regulation of intracellular pH in eukaryotic cells. Biochem J 250:1–8. https://doi.org/10.1042/bj2500001

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  205. Nunes P, Guido D, Demaurex N (2015) Measuring phagosome pH by ratiometric fluorescence microscopy. J Vis Exp 53402. https://doi.org/10.3791/53402

  206. Asokan A, Cho MJ (2002) Exploitation of intracellular pH gradients in the cellular delivery of macromolecules. J Pharm Sci 91:903–913. https://doi.org/10.1002/jps.10095

    Article  CAS  PubMed  Google Scholar 

  207. Porcelli AM, Ghelli A, Zanna C, Pinton P, Rizzuto R, Rugolo M (2005) pH difference across the outer mitochondrial membrane measured with a green fluorescent protein mutant. Biochem Biophys Res Commun 326:799–804. https://doi.org/10.1016/j.bbrc.2004.11.105

    Article  CAS  PubMed  Google Scholar 

  208. Wilson AF, Simmons DH (1970) Organ and whole body cell pH. Proc Soc Exp Biol Med 134:127–130. https://doi.org/10.3181/00379727-134-34743

    Article  CAS  PubMed  Google Scholar 

  209. Park HJ, Lim CS, Kim ES, Han HJ, Lee TH, Chun HJ, Cho BR (2012) Measurement of pH values in human tissues by two-photon microscopy. Angew Chem Int Ed 51:2673–2676. https://doi.org/10.1002/anie.201109052

    Article  CAS  Google Scholar 

  210. Persi E, Duran-Frigola M, Damaghi M, Roush WR, Aloy P, Cleveland JL, Gillies RJ, Ruppin E (2018) Systems analysis of intracellular pH vulnerabilities for cancer therapy. Nat Commun 9:2997. https://doi.org/10.1038/s41467-018-05261-x

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  211. Radi R (2018) Oxygen radicals, nitric oxide, and peroxynitrite: redox pathways in molecular medicine. Proc Natl Acad Sci U S A 115:5839–5848. https://doi.org/10.1073/pnas.1804932115

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  212. Hu X, Dong D, Xia M, Yang Y, Wang J, Su J, Sun L, Yu H (2020) Oxidative stress and antioxidant capacity: development and prospects. New J Chem 44:11405–11419. https://doi.org/10.1039/D0NJ02041A

    Article  CAS  Google Scholar 

  213. Di Meo S, Reed TT, Venditti P, Victor VM (2016) Role of ROS and RNS sources in physiological and pathological conditions. Oxid Med Cell Longev 2016:1245049.  https://doi.org/10.1155/2016/1245049

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  214. Zhang Y, Wong HS (2021) Are mitochondria the main contributor of reactive oxygen species in cells. J Exp Biol 224:jeb221606. https://doi.org/10.1242/jeb.221606

    Article  PubMed  Google Scholar 

  215. Neha K, Haider MR, Pathak A, Yar MS (2019) Medicinal prospects of antioxidants: a review. Eur J Med Chem 178:687–704. https://doi.org/10.1016/j.ejmech.2019.06.010

    Article  CAS  PubMed  Google Scholar 

  216. Pisoschi AM, Pop A, Iordache F, Stanca L, Predoi G, Serban AI (2021) Oxidative stress mitigation by antioxidants—an overview on their chemistry and influences on health status. Eur J Med Chem 209:112891. https://doi.org/10.1016/j.ejmech.2020.112891

    Article  CAS  PubMed  Google Scholar 

  217. Jungwirth U, Kowol CR, Keppler BK, Hartinger CG, Berger W, Heffeter P (2011) Anticancer activity of metal complexes: involvement of redox processes. Antioxidant Redox Signal 15:1085–1127. https://doi.org/10.1089/ars.2010.3663

    Article  CAS  Google Scholar 

  218. Eteshola EOU, Haupt DA, Koos SI, Siemer LA, Morris DL (2020) The role of metal ion binding in the antioxidant mechanisms of reduced and oxidized glutathione in metal-mediated oxidative DNA damage. Metallomics 79–91. https://doi.org/10.1039/C9MT00231F

  219. Ouyang Y, Peng Y, Li J, Holmgren A, Lu J (2018) Modulation of thiol-dependent redox system by metal ions via thioredoxin and glutaredoxin systems. Metallomics 10:218–228. https://doi.org/10.1039/C7MT00327G

    Article  CAS  PubMed  Google Scholar 

  220. Arunachalam V, Tummanapelli AK, Vasudevan S (2019) The multiple dissociation constants of glutathione disulfide: interpreting experimental pH-titration curves with: ab initio MD simulations. Phys Chem Chem Phys 21:9212–9217. https://doi.org/10.1039/C9CP00761J

    Article  CAS  PubMed  Google Scholar 

  221. Falcone E, Ritacca AG, Hager S, Schueffl H, Vileno B, Khoury YE, Hellwig P, Kowol CR, Heffeter P, Sicilia E, Faller P (2022) Copper-catalyzed glutathione oxidation is accelerated by the anticancer thiosemicarbazone Dp44mT and further boosted at lower pH. J Am Chem Soc 144:14758–14768. https://doi.org/10.1021/jacs.2c05355

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  222. Nutting LA, Weber EM, Tryon JL (1967) Metabolic removal of sulfur from 1-methylisatin 3-thiosemicarbazone. J Virol 1:650–651. https://doi.org/10.1128/jvi.1.3.650-651.1967

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  223. Creasey WA, Agrawal KC, Capizzi RL, Stinson KK, Sartorelli AC (1972) Studies of the antineoplastic activity and metabolism of α-(N)-heterocyclic carboxaldehyde thiosemicarbazones in dogs and mice. Cancer Res 32:565–572

    CAS  PubMed  Google Scholar 

  224. DeConti RC, Toftness BR, Agrawal KC, Tomchick R, Mead JA, Bertino JR, Sartorelli AC, Creasey WA (1972) Clinical and pharmacological studies with 5-hydroxy-2-formylpyridine thiosemicarbazone. Cancer Res 32:1455–1462

    CAS  PubMed  Google Scholar 

  225. Pelivan K, Frensemeier L, Karst U, Koellensperger G, Bielec B, Hager S, Heffeter P, Kepplerae BK, Kowol CR (2017) Understanding the metabolism of the anticancer drug Triapine®: electrochemical oxidation, microsomal incubation and: In vivo analysis using LC-HRMS. Analyst 142:3165–3176. https://doi.org/10.1039/C7AN00902J

    Article  CAS  PubMed  Google Scholar 

  226. Stariat J, Šesták V, Vávrová K, Nobilis M, Kollárová Z, Klimeš J, Kalinowski DS, Richardson DR, Kovaříková P (2012) LC-MS/MS identification of the principal in vitro and in vivo phase I metabolites of the novel thiosemicarbazone anti-cancer drug, Bp4eT. Anal Bioanal Chem 403:309–321. https://doi.org/10.1007/s00216-012-5766-4

    Article  CAS  PubMed  Google Scholar 

  227. Sestak V, Stariat J, Cermanova J, Potuckova E, Chladek J, Roh J, Bures J, Jansova H, Prusa P, Sterba M, Micuda S, Simunek T, Kalinowski DS, Richardson DR, Kovarikova P (2015) Novel and potent anti-tumor and anti-metastatic di-2-pyridylketone thiosemicarbazones demonstrate marked differences in pharmacology between the first and second generation lead agents. Oncotarget 6:42411–42428. https://doi.org/10.18632/oncotarget.6389

    Article  PubMed  PubMed Central  Google Scholar 

  228. Agrawal KC, Sartorelli AC (1969) Potential antitumor agents. II. Effects of modifications in the side chain of 1-formylisoquinoline thiosemicarbazone. J Med Chem 12:771–774. https://doi.org/10.1021/jm00305a011

    Article  CAS  PubMed  Google Scholar 

  229. Kalinowski DS, Sharpe PC, Bernhardt PV, Richardson DR (2007) Design, synthesis, and characterization of new iron chelators with anti-proliferative activity: structure–activity relationships of novel thiohydrazone analogues. J Med Chem 50:6212–6225. https://doi.org/10.1021/jm070839q

    Article  CAS  PubMed  Google Scholar 

  230. Richardson DR, Sharpe PC, Lovejoy DB, Senaratne D, Kalinowski DS, Islam M, Bernhardt PV (2006) Dipyridyl thiosemicarbazone chelators with potent and selective antitumor activity form iron complexes with redox activity. J Med Chem 49:6510–6521. https://doi.org/10.1021/jm0606342

    Article  CAS  PubMed  Google Scholar 

  231. Potůčková E, Roh J, Macháček M, Sahni S, Stariat J, Šesták V, Jansová H, Hašková P, Jirkovská A, Vávrová K, Kovaříková P, Kalinowski DS, Richardson DR, Šimůnek T (2015) In vitro characterization of the pharmacological properties of the anti-cancer chelator, Bp4eT, and its phase I metabolites. PLoS ONE 10:e0139929. https://doi.org/10.1371/journal.pone.0139929

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  232. Boström J, Hogner A, Llinàs A, Wellner E, Plowright AT (2012) Oxadiazoles in medicinal chemistry. J Med Chem 55:1817–1830. https://doi.org/10.1021/jm2013248

    Article  CAS  PubMed  Google Scholar 

  233. Raab A, Feldmann J (2019) Biological sulphur-containing compounds – Analytical challenges. Anal Chim Acta 1079:20–29. https://doi.org/10.1016/j.aca.2019.05.064

    Article  CAS  PubMed  Google Scholar 

  234. Komarnisky LA, Christopherson RJ, Basu TK (2003) Sulfur: its clinical and toxicologic aspects. Nutrition 19:54–61. https://doi.org/10.1016/S0899-9007(02)00833-X

    Article  CAS  PubMed  Google Scholar 

  235. Markovich D (2001) Physiological roles and regulation of mammalian sulfate transporters. Physiol Rev 81:1499–1533. https://doi.org/10.1152/physrev.2001.81.4.1499

    Article  CAS  PubMed  Google Scholar 

  236. Takano Y, Shimamoto K, Hanaoka K (2016) Chemical tools for the study of hydrogen sulfide (H2S) and sulfane sulfur and their applications to biological studies. J Clin Biochem Nutr 58:7–15. https://doi.org/10.3164/jcbn.15-91

    Article  CAS  PubMed  Google Scholar 

  237. Pavlik JW, Noll BC, Oliver AG, Schulz CE, Scheidt WR (2010) Hydrosulfide (HS−) coordination in iron porphyrinates. Inorg Chem 49:1017–1026. https://doi.org/10.1021/ic901853p

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

This work was supported by European Union H2020-LC-SC3-2020-NZE-RES-CC NEFERTITI, NMBP-16-2020-GA 953152 DIAGONAL, DT-NMBP-04-2020-GA 952941 BIOMAC and HORIZON-CL4-2021-RESILIENCE-01-12 Projects, together with Ministerio de Ciencia, Innovación y Universidades PID2021-127531NB-I00 (AEI/https://doi.org/10.13039/501100011033/FEDER, UE) and CTQ(QMC) RED2018-102471-T MultiMetDrugs Network (Spain), Consejería de Educación de la Junta de Castilla y León and FEDER BU049P20, Consellería de Cultura, Educación e Ordenación Universitaria, Xunta de Galicia GRC GI-1584 (ED431C 2023/02). AJP wishes to thank the Consejería de Educación de la Junta de Castilla y León and the Fondo Social Europeo Plus (FSE +) for her Doctoral Contract and to ICCRAM for the financial support.

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Authors and Affiliations

  1. Departamento de Química, Facultad de Ciencias, Universidad de Burgos, 09001, Burgos, Spain

    Alondra Jiménez-Pérez & Javier García-Tojal

  2. Departamento de Química Inorgánica, Facultade de Química, Campus Vida, Universidade de Santiago de Compostela, 15782, Santiago de Compostela, Spain

    Sandra Fernández-Fariña & Rosa Pedrido

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  1. Alondra Jiménez-Pérez
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  2. Sandra Fernández-Fariña
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  3. Rosa Pedrido
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  4. Javier García-Tojal
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RP and JGT contributed to the idea, conception, and design of the present work. All the authors performed the literature search and analysis, and equally contributed to the writing of this manuscript. All the authors read and approved the final manuscript.

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Correspondence to Rosa Pedrido or Javier García-Tojal.

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Jiménez-Pérez, A., Fernández-Fariña, S., Pedrido, R. et al. Desulfurization of thiosemicarbazones: the role of metal ions and biological implications. J Biol Inorg Chem 29, 3–31 (2024). https://doi.org/10.1007/s00775-023-02037-7

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