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Synthesis, characterization, cytotoxic and antitubercular activities of new gold(I) and gold(III) complexes containing ligands derived from carbohydrates

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Abstract

Novel gold(I) and gold(III) complexes containing derivatives of d-galactose, d-ribose and d-glucono-1,5-lactone as ligands were synthesized and characterized by IR, 1H, and 13C NMR, high resolution mass spectra and cyclic voltammetry. The compounds were evaluated in vitro for their cytotoxicity against three types of tumor cells: cervical carcinoma (HeLa) breast adenocarcinoma (MCF-7) and glioblastoma (MO59J) and one non-tumor cell line: human lung fibroblasts (GM07492A). Their antitubercular activity was evaluated as well expressed as the minimum inhibitory concentration (MIC90) in μg/mL. In general, the gold(I) complexes were more active than gold(III) complexes, for example, the gold(I) complex (1) was about 8.8 times and 7.6 times more cytotoxic than gold(III) complex (8) in MO59J and MCF-7 cells, respectively. Ribose and alkyl phosphine derivative complexes were more active than galactose and aryl phosphine complexes. The presence of a thiazolidine ring did not improve the cytotoxicity. The study of the cytotoxic activity revealed effective antitumor activities for the gold(I) complexes, being more active than cisplatin in all the tested tumor cell lines. Gold(I) compounds (1), (2), (3), (4) and (6) exhibited relevant antitubercular activity even when compared with first line drugs such as rifampicin.

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Fig. 1
Scheme 1
Scheme 2
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Fig. 2
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Abbreviations

IR:

Infrared

NMR:

Nuclear magnetic resonance

TMS:

Tetramethylsilane

Isop:

Isopropylidene

DMF:

Dimethyl formamide

HEPES:

4-(2-Hydroxyethyl)piperazine-1-ethanesulfonic acid, N-(2-hydroxyethyl)piperazine-N′-(2-ethanesulfonic acid)

HMRS(ESI):

High-resolution mass spectra (eletrospray ionization)

HAM-F10:

Nutrient mixture F-10

DMEM:

Dulbecco’s modified Eagle’s medium

XTT:

2,3-Bis-(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide

DMSO:

Dimethylsulfoxide

PBS:

Phosphate buffer saline

References

  • Al-Jaroudi S, Monim-ul-Mehboob M, Altaf M, Al-Saadi AA, Wazeer MIM, Altuwaijri S, Isab AA (2014) Synthesis, spectroscopic characterization, electrochemical behavior and computational analysis of mixed diamine ligand gold(III) complexes: antiproliferative and in vitro cytotoxic evaluations against human cancer cell lines. Biometals 27:1115–1136

    Article  CAS  PubMed  Google Scholar 

  • Al-Maythalony BA, Wazeer MIM, Isab AA (2009) Synthesis and characterization of gold(III) complexes with alkyldiamine ligands. Inorg Chim Acta 362:3109–3113

    Article  CAS  Google Scholar 

  • Almeida MV, Cesar ET, Fontes APS, Felício ECA (2000) Synthesis of platinum complexes from sugar derivatives. J Carbohydr Chem 19:323–329

    Article  Google Scholar 

  • Al-Thebeiti MS (1999) Regiocontrolled incorporation and annulation of glucose into spirothiazole and spirothiazoloxazole derivatives. J Carbohydr Chem 18:667–674

    Article  CAS  Google Scholar 

  • Amarante GW (2005) Síntese de Compostos Anfifílicos derivados da d-Galactose, Potenciais Agentes Surfactantes. Dissertação, Universidade Federal de Juiz de Fora

  • Baenziger NC, Bennet WE, Soboroff DM (1976) Chloro(triphenylphosphine)god(I). Acta Cryst B 32:962

    Article  Google Scholar 

  • Barnard PJ, Berners-Price SJ (2007) Targeting the mitochondrial cell death pathway with gold compounds. Coord Chem Rev 251:1889–1902

    Article  CAS  Google Scholar 

  • Benedek TG (2004) The history of gold therapy for tuberculosis. J Hist Med Allied Sci 59:50–89

    Article  PubMed  Google Scholar 

  • Brown FC (1961) 4-Thiazolidinones. Chem Rev 61:464–521

    Article  Google Scholar 

  • Bruni B, Guerri A, Marcon G, Messori L, Orioli P (1999) Structure and cytotoxic properties of some selected gold(III) complexes. Croat Chem Acta 72:221–229

    CAS  Google Scholar 

  • Canetti J, Rist E, Grosset R (1963) Measurement of sensitivity of the tuberculous bacillus to antibacillary drugs by the method of proportions. Methodology, resistance criteria, results and interpretation. Rev Tuberc Pneumol 27:217–272

    CAS  Google Scholar 

  • Casseta MI, Marzo T, Fallani S, Novelli A, Messori L (2014) Drug repositioning: auranofin as a prospective antimicrobial agent for the treatment of severe staphylococcal infections. Biometals 27:787–791

    Article  Google Scholar 

  • Chaves JDS, Neumann F, Francisco TM, Corrêa CC, Lopes MTP, Silva H, Fontes APS, Almeida MV (2014) Synthesis and cytotoxic activity of god(I) complexes containing phosphines and 3-benzyl-1,3-thiazolidine-2-thione or 5-phenyl-1,3,4-oxadiazole-2-thione as ligands. Inorg Chim Acta 414:85–90

    Article  CAS  Google Scholar 

  • Chen H, Jiao L, Guo Z, Li X, Ba C, Zhang J (2008) Synthesis and biological activity of novel thiazolidin-4-ones with a carbohydrate moiety. Carbohydr Res 343:3015–3020

    Article  CAS  PubMed  Google Scholar 

  • Chirullo B, Sgarbanti R, Limongi D, Shytaj IL, Alvarez D, Das B, Boe A, Da Fonseca S, Chomont N, Liotta L, Petricoin E III, Norelli S, Pelosi E, Garaci E, Savarino A, Palamara AT (2013) A candidate anti-HIV reservoir compound, auranofin, exerts a selective ‘anti-memory’ effect by exploiting the baseline oxidative status of lymphocytes. Cell Death Dis 4:1–12

    Article  Google Scholar 

  • Coates GE, Kowala C, Swan JM (1966) Coordination compounds of Group IB metals. I. Triethylphosphine complexes of gold(I) mercaptides. Aust J Chem 19:539–545

    Article  CAS  Google Scholar 

  • Cuin A, Massabni AC, Pereira GA, Leite CQF, Pavan FR, Sesti-Costa R, Heinrich TA, Costa-Neto CM (2011) 6-Mercaptopurine complexes with silver and gold ions: anti-tuberculosis and anti-cancer activities. Biomed Pharmacother 65:334–338

    Article  CAS  PubMed  Google Scholar 

  • Debnath A, Parsonage D, Andrade RM, He C, Cobo ER, Hirata K, Chen S, Rivera-García G, Orozco E, Martínez M, Guntilleke S, Barrios AM, Arkin MR, Poole LB, Mckerrow JH, Reed S (2012) A high throughput drug screen for Entamoeba histolytica identifies a new lead and target. Nat Med 18:956–960

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Delaunay D, Toupet L, Le Corre M (1995) Reactivity of/β-amino alcohols with carbon disulfide. Study on the synthesis of 2-oxazolidinethiones and 2-thiazolidinethiones. J Org Chem 60:6604–6607

    Article  CAS  Google Scholar 

  • Eisler R (2003) Chrysotherapy: a synoptic review. Inflamm Res 52:487–501

    Article  CAS  PubMed  Google Scholar 

  • Eiter LC, Hall NW, Day CS, Saluta G, Kucera GL, Bierbach U (2009) Gold(I) analogues of a platinum-acridine antitumor agent are only moderately cytotoxic bus show potent activity against Mycobacterium tuberculosis. J Med Chem 52:6519–6522

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Franzblau SG, Witzig RS, McLaughlin JC, Torres P, Madico G, Hernandez A, Degnan MT, Cook MB, Quenzer VK, Fergu-son RM, Gilman RH (1998) Rapid, low-technology MIC determination with clinical Mycobacterium tuberculosis isolates by using the microplate Alamar Blue Assay. J Clin Microbiol 36:362–366

    PubMed Central  CAS  PubMed  Google Scholar 

  • Gabbiani C, Casini A, Messori L (2007) Gold(III) compounds as anticancer drugs. Gold Bull 40:73–81

    Article  CAS  Google Scholar 

  • Garegg PJ (1984) Some aspects of régio-stereo-, and chemoselective reactions in carbohydrate chemistry. Pure Appl Chem 56:845–858

    Article  CAS  Google Scholar 

  • Gyepes A, Schaffer R, Bajor G, Woller A, Fodor P (2008) Synthesis and chromatographic study of methyl-2,3-O-isopropylidene-5-dimethyl-arsinoyl-β-d-ribofuranoside and methyl-2,3-O-isopropylidene-5-deoxy-5-dimethyl-thioarsinoyl-β-d-ribofuranoside. Polyhedron 27:2655–2661

    Article  CAS  Google Scholar 

  • Hickey JL, Ruhayel RA, Barnard PJ, Baker MV, Berners-Price SJ, Filipovska A (2008) Mitochondria-targeted chemotherapeutics: the rational design of gold(I) N-heterocyclic carbene complexes that are selectively toxic to cancer cells and target protein selenols in preference to thiols. J Am Chem Soc 130:12570–12571

    Article  CAS  PubMed  Google Scholar 

  • Ingles DL, Whistler RL (1962) Preparation of several methyl d-pentothiapyranosides. J Org Chem 27:3896–3898

    Article  CAS  Google Scholar 

  • Lessa JA, Ferraz KSO, Guerra JC, De Miranda LF, Romeiro CFD, Souza-Fagundes EM, Barbeira PJS, Beraldo H (2012) Spectroscopic and electrochemical characterization of gold(I) and gold(III) complexes with glyoxaldehyde bis(thiosemicarbazones): cytotoxicity against human tumor cell lines and inhibition of thioredoxin reductase activity. Biometals 25:587–598

    Article  CAS  PubMed  Google Scholar 

  • Maiore L, Cinellu MA, Nobili S, Landini I, Mini E, Gabbiani C, Messori L (2012) Gold(III) complexes with 2-substituted pyridines as experimental anticancer agents: solution behavior, reactions with model proteins, antiproliferative properties. J Inorg Biochem 108:123–127

    Article  CAS  PubMed  Google Scholar 

  • Messori L, Marcon G (2004) Gold complexes as antitumor agents. Met Ions Biol 42:385–424

    CAS  Google Scholar 

  • Messori L, Francesco A, Marcon G, Orioli P, Fontani M, Mini E, Mazzei T, Carott S, O’connell T, Zanello P (2000) Gold(III) complexes as potential antitumor agents: solution chemistry and cytotoxic properties of some selected gold(III) compounds. J Med Chem 43:3541–3548

    Article  CAS  PubMed  Google Scholar 

  • Mirabelli CK, Johson RK, Sung CM, Faucette L, Muirhead K, Crooke ST (1985) Models cytotoxic properties of auranofin, a coordinated gold in vitro antitumor activity and in vivo evaluation. Cancer Res 45:32–39

    CAS  PubMed  Google Scholar 

  • Mirabelli CK, Johson RK, Hill DT, Faucette L, Girard GR, Kuo GY, Sung CM, Crooke ST (1986) Correlation of the in vitro cytotoxic and in vivo antitumor activities of gold(I) coordination complexes. J Med Chem 29:218–223

    Article  CAS  PubMed  Google Scholar 

  • Navarro M (2009) Gold complexes as potential anti-parasitic agentes. Coord Chem Rev 253:1619–1626

    Article  CAS  Google Scholar 

  • Ott I (2009) On the medicinal chemistry of gold complexes as anticancer drugs. Coord Chem Rev 253:1670–1681

    Article  CAS  Google Scholar 

  • Ott I, Qian X, Xu Y, Vlecken DHW, Marques IJ, Kubutat D, Sheldrick WS, Jesse P, Prokop A, Bagowski CP (2009) A gold(I) phosphine complex containing a naphthalimide ligand functions as a TrxR inhibiting antiproliferative agent and angiogenesis inhibitor. J Med Chem 52:763–770

    Article  CAS  PubMed  Google Scholar 

  • Rauter AP, Padilha M, Figueiredo JA, Ismael MI, Justino J, Ferreira H, Ferreira MJ, Rajendran C, Wilkins R, Vaz PD, Calhorda MJJ (2005) Bioactive pseudo-C-nucleosides containing thiazole, theazolidinone, and tetrazole rings. Carbohydr Chem 24:275–296

    Article  CAS  Google Scholar 

  • Reis RS, Ijr Neves, Lourenço SLS, Fonseca LS, Lourenço MCS (2004) Comparison of flow cytometric and Alamar Blue Tests with the proportional method for testing susceptibility of Mycobacterium tuberculosis to rifampin and isoniazid. Clin Microbiol 42:2247–2248

    Article  CAS  Google Scholar 

  • Releling H, Rouville E, Chittenden GJF (1987) The chemistry of d-gluconic acid derivatives. Part 1. Synthesis of 3,4;5,6-di-O-isopropylidene-d-glucitol and 2,3;4,5-di-O-isopropylidene-aldehydo-d-arabinose from d-glucono-1,5-lactone. Rec Trav Chim Pays-Bas 106:461–464

    Article  Google Scholar 

  • Rigobello MP, Messori L, Marcon G, Bragadin M, Folda A, Scutari G, Bindoli A (2004) Gold complexes inhibit mitochondrial thioredoxin reductase: consequences on mitochondrial functions. J Inorg Biochem 98:1634–1641

    Article  CAS  PubMed  Google Scholar 

  • Sadler PJ, Nasr M, Narayanan VL (1984) In: Douple EB, Krakhoff IH, Hacker MP (eds) Platinum coordination complexes in cancer chemotherapy. Martinus Nijhoff Publishers, Boston, pp 290–304

    Chapter  Google Scholar 

  • Shi J-C, Chen L-J, Huang S-Y, Wu D-X, Kang B-S (1997) Chiral phosphine ligands derived from sugars 10. Syntheses, structure, characterization and activity of the gold(I) complexes with sugar-substructure phosphine ligands. J Organomet Chem 535:17–23

    Article  CAS  Google Scholar 

  • Shoeib T, Atkinson DW, Sharp BL (2010) Structural analysis of the anti-arthritic drug Auranofin: its complexes with cysteine, selenocysteine and their fragmentation products. Inorg Chim Acta 363:184–192

    Article  CAS  Google Scholar 

  • Simon TM, Kunishima DH, Vibert GJ, Lorber A (1979) Inhibitory effects of a new oral gold compound on hela cells. Cancer 44:1965–1975

    Article  CAS  PubMed  Google Scholar 

  • Simon TM, Kunishima DH, Vibert GJ, Lorber A (1981) Screening trial with the coordinated gold compound auranofin using mouse lymphocytic leukemia P3881. Cancer Res 41:94–97

    CAS  PubMed  Google Scholar 

  • Sout EI, Doane WM, Russell CR, Jones LB (1975) Photolysis of some carbohydrate dithiobis(thioformates). J Org Chem 40:1331–1336

    Article  Google Scholar 

  • Sun RW-Y, Che C-M (2009) The anti-cancer properties of gold(III) compounds with dianionic porphyrin and tetradentate ligands. Coord Chem Rev 253:1682–1691

    Article  CAS  Google Scholar 

  • Tiekink ERT (2002) Gold derivatives for the treatment of cancer. Crit Ver Oncol Hematol 42:225–248

    Article  Google Scholar 

  • Trávnicek Z, Starha P, Vanco J, Hosek SJ, Suchý PJ, Prazanová G (2012) Anti-inflammatory active gold(I) complexes involving 6-substituted-purine derivatives. J Med Chem 55:4568–4579

    Article  PubMed  Google Scholar 

  • Tsubomura T, Yano S, Kobayashi K, Sakurai T, Yoshikawa S (1986) First synthesis and characterization of platinum(II) complexes of amino sugars having anti-tumour activity; crystal structure of [ptcl2(methyl 2,3-dideoxy-α-d-mannopyranoside)] H2O. J Chem Soc Chem Commun 6:459–460

    Article  Google Scholar 

  • Vanitha JD, Paramasivan CN (2004) Evaluation of microplate Alamar blue assay for drug susceptibility testing of Mycobacterium avium complex isolates. Diagn Microbiol Infect Dis 49:179–180

    Article  CAS  PubMed  Google Scholar 

  • Yoshida S-I, Kato T, Sakurada S, Kurono C, Yang J-P, Matsui N, Soji T, Okamato T (1999) Inhibition of IL-6 and IL-8 induction from cultured rheumatoid synovial fibroblasts by treatment with aurothioglucose. Int Immunol 11:151–158

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

The authors thank FAPEMIG, CAPES and CNPq for financial support. This work is a collaboration research project of members of the Rede Mineira de Química (RQ-MG) supported by FAPEMIG (Project: CEX—RED-0010-14).

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Authors and Affiliations

  1. Departamento de Química, ICE, Universidade Federal de Juiz de Fora, Juiz de Fora, MG, 36036-330, Brazil

    Joana Darc Souza Chaves, Gustavo Chevitarese Azevedo, Renato Camargo Matos, Heveline Silva, Ana Paula Soares Fontes & Mauro Vieira de Almeida

  2. Departamento de Pesquisas com Produtos Naturais, Universidade de Franca, Franca, SP, 14406-600, Brazil

    Jaqueline Lopes Damasceno, Marcela Cristina Ferreira Paula, Pollyanna Francielli de Oliveira & Denise Crispim Tavares

  3. Instituto de Tecnologia em Fármacos-Far Manguinhos, Fundação Oswaldo Cruz, Rio de Janeiro, RJ, 21041-250, Brazil

    Maria Cristina S. Lourenço

Authors
  1. Joana Darc Souza Chaves
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  2. Jaqueline Lopes Damasceno
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  3. Marcela Cristina Ferreira Paula
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  4. Pollyanna Francielli de Oliveira
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  5. Gustavo Chevitarese Azevedo
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  6. Renato Camargo Matos
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  7. Maria Cristina S. Lourenço
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  8. Denise Crispim Tavares
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  9. Heveline Silva
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  10. Ana Paula Soares Fontes
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  11. Mauro Vieira de Almeida
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Correspondence to Mauro Vieira de Almeida.

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Chaves, J.D.S., Damasceno, J.L., Paula, M.C.F. et al. Synthesis, characterization, cytotoxic and antitubercular activities of new gold(I) and gold(III) complexes containing ligands derived from carbohydrates. Biometals 28, 845–860 (2015). https://doi.org/10.1007/s10534-015-9870-8

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