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Structure–activity relationship study of thiosemicarbazones on an African trypanosome: Trypanosoma brucei brucei

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Abstract

To explore the structure–activity relationships of thiosemicarbazones on African trypanosome: Trypanosoma brucei brucei, a series of thirty-five thiosemicarbazones (1–35) have been synthesized and characterized by their 1H NMR, 13C NMR, and FT-IR spectra. All compounds were tested for trypanocidal activity using the method “Lilit alamar blue”. The comparison of trypanocidal power of thiosemicarbazones was performed considering their structures. This study that was done using acetophenone thiosemicarbazone (1) as basic model, showed that: (a) the presence of lipophilic substituents in para position on benzene ring, (b) substitution of benzene ring and (c) substitution of hydrogen of thioamide function by a phenyl, strongly influence trypanocidal activity. The various modifications to basic structure (1) allowed the synthesis of 1-(4-chlorophenyl) ethylidene-4-phenyl-thiosemicarbazide (34). With a trypanocidal activity of 3.97 μM, this compound is the most active of the series.

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References

  • Afrasiabi Z, Sinn E, Padhye S, Dutta S, Newton C, Anson CE, Powell AK (2003) Transition metal complexes of phenanthrenequinone thiosemicarbazone as potential anticancer agents: synthesis, structure, spectroscopy, electrochemistry and in vitro anticancer activity against human breast cancer cell-line T47D. J Inorg Biochem 95(4):306–314

    Article  PubMed  CAS  Google Scholar 

  • Afrasiabi Z, Sinn E, Chen JN, Ma YF, Rheingold AL, Zakharov LN, Rath N, Padhye S (2004) Appended 1,2-naphthoquinones as anticancer agents 1: synthesis, structural, spectral and antitumor activities of ortho-naphthoquinone thiosemicarbazone and its transition metal complexes. Inorg Chim Acta 357(1):271–278

    Article  CAS  Google Scholar 

  • Aguirre G, Boiani M, Cerecetto H, Gerpe A, Gonzalez M, Sainz YF, Denicola A, Ocariz CO, Nogal JJ, Montero D (2004) In vitro activity and mechanism of action against the protozoan parasite Trypanosoma cruzi of 5-nitrofuryl containing thiosemicarbazones. Bioorg Med Chem 12:4885–4893

    Article  PubMed  CAS  Google Scholar 

  • Baltz T, Baltz D, Giroud C, Crockett J (1985) Cultivation in a semi defined medium of animal infective forms of Trypanosoma brucei, T. equiperdum, T. evansi, T. rhodhesiense et T.gambiense. EMBO J 4(5):1273–1277

    PubMed  CAS  Google Scholar 

  • Chapleo CB, Myers PL, Smith ACB, Stillings MR, Tulloch IF, Walter SD (1988) Substituted 1,3,4-thiadiazolines with anticonvulsant activity. 4. Amidines. J Med Chem 31:7

    Article  PubMed  CAS  Google Scholar 

  • Du X, Guo C, Hansell E, Doyle PS, Caffrey CR, Holler TP, Mckerrow JH, Cohen FE (2002) Synthesis and structure–activity relationship study of potent trypanocidal thio semicarbazone inhibitors of the trypanosomal cysteine protease cruzain. J Med Chem 45:2695–2707

    Article  PubMed  CAS  Google Scholar 

  • Easmon J, Purstinger G, Heinisch G, Roth T, Fiebig HH, Holzer W, Jäger W, Jenny M, Hofmann J (2001) Synthesis, cytotoxicity, and antitumor activity of copper (II) and iron (II) complexes of (4) N-azabicyclo [3. 2. 2] nonane thiosemicarbazones derived from acyldiazines. Med Chem 44:2164

    Article  CAS  Google Scholar 

  • Fujii N, Mallari JP, Hansell EJ, Mackey Z, Doyle P, Zhou YM, Gut J, Rosenthal PJ, McKerrow JH, Guy RK (2005) Dicovery of potent thiosemicarbazones inhibitors of rhodesain and cruzain. Bioorg Med Chem Lett 15:121–123

    Article  PubMed  CAS  Google Scholar 

  • Garcia CC, Brousse BN, Carlucci MJ, Moglioni AG, Martins AM, Moltrasio GY, D’Accorso NB, Damonte EB (2003) Inhibitory effect of thiosemicarbazone derivatives on Junin virus replication in vitro. Antivir Chem Chemother 14:99–105

    PubMed  CAS  Google Scholar 

  • Hall IH, Lachey CB, Kistler TD, Durham RW, Jouad EM, Khan M, Thanh XD, Djebbar-Sid S, Benali-Baitich O, Bouet GM (2000) Cytotoxicity of copper and cobalt complexes of furfural semicarbazone and thiosemicarbazone derivatives in murine and human tumor cell lines. Pharmazie 55(12):937–941

    PubMed  CAS  Google Scholar 

  • Hirumi K (1994) Axenic culture et African trypanosome bloodstream forms. Parasitol Today 10(2):80–84

    Article  PubMed  CAS  Google Scholar 

  • Kasuga NC, Sekino K, Ishibawa (2003) Synthesis, crystal structures and antibacterial activity of monomeric 7-cordinate bismuth (III) complexes with tridentate and pentadentate thiosemicarbazones ligand. Inorg Biochem 96:298

    Article  CAS  Google Scholar 

  • Klayman DL, Scovill JP, Bruce J, Bartosevich JF (1984) 2-Acethylpyridine thiosemicarbazones derivatives of acethylisoquinoline as potential antimalarial agents. J Med Chem 27:84

    Article  PubMed  CAS  Google Scholar 

  • Kovala-Demertzi D, Demertzis MA, Miller JR, Papadopoulou C, Dodorou C, Filousis G (2002) Structure of bis(2-acetylpyridine 3-hexamethyleneiminylthiosemicarbazonato) palladium (II), a potential antitumor complex. J Inorg Biochem 92:137

    Article  PubMed  CAS  Google Scholar 

  • Lipinski CA, Lombardo F, Dominy BW, Feeney PJ (1997) Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings. Adv Drug Delivery Rev 23:3–25

    Article  CAS  Google Scholar 

  • Pandeya SN, Mishra Y, Singh PN, Rupainwar DC (1998) Anticonvulsant activity of thioureido derivatives of acetophenone semicarbazone. Pharmacol Res 37:17

    Article  PubMed  CAS  Google Scholar 

  • Pandeya SN, Aggarwal N, Jain JS (1999) Evaluation of semicarbazones for anticonvulsant and sedative-hypnotic properties. Pharmazie 54:300

    PubMed  CAS  Google Scholar 

  • Perez JM, Matesanz AI, Martin A, Navaro P, Alonso C, Sousa P (1999) Synthesis and characterization of complexes of p-isopropylbenzaldehyde and methyl 2-pyridyl ketone thiosemicarbazones with Zn(II) and Cd(II) metallic centers. Cytotoxic activity and induction of apoptosis in Pam-ras cells. J Inorg Biochem 75:255–261

    Article  PubMed  CAS  Google Scholar 

  • Quiroga AG, Pérez JM, López-Solera I, Montero EI, Masaguer JR, Luque A, Román P, Edwards A, Alonso C, Navarro-Ranninger C (1998) Novel tetranuclear orthometalated complexes of Pd (II) and Pt(II) derived from p-isopropylbenzaldehyde thiosemicarbazone with cytotoxic activity in cis-DDP resistant tumor cell lines. Interaction of these complexes with DNA. J Med Chem 41(9):1399–1408

    Article  PubMed  CAS  Google Scholar 

  • Räz B, Ten M, Grether-Bühler Y, Kaminsky R, Brun R (1997) The Alamar cylamino BlueR essay to determine drugs sensitivity of African trypanosomes (T. b rhodhesiense et T. b gambiense) in vitro. Acta Trop 68:139–147

    Article  PubMed  Google Scholar 

  • Rebolledo AP, de Lima GM, Gambi LN, Speziali NL, Maia DF, Pinheiro CB, Ardisson JD, Cortes ME, Beraldo Hl (2003) Tin (IV) complexes of 2-benzoylpyridine N (4)-phenylthiosemicarbazone: spectral characterization, structural studies and antifungal activity. Appl Organomet Chem 17:945

    Article  CAS  Google Scholar 

  • Sau DK, Butcher RJ, Chandhuri S, Saha N (2003) Spectroscopic, structural and antibacterial properties of copper (II) complexes with bio-relevant 5-methyl-3-formylpyrazole N(4)-benzyl-N(4) methylthiosemicarbazone. Mol Cell Biochem 253(1–2):21–22

    Article  PubMed  CAS  Google Scholar 

  • Tiuman TS, Ueda-Nakamura T, Garcia Cortez DA, Dias Filho BP, Morgado-Diaz JA, de Souza W, Nakamura CV (2005) Antileishmanial activity of Parthenolide, a sesquiterpene lactone isolated from Tanacetum parthenium. Antimic Agents chemother 49:176–182

    Google Scholar 

  • Williamson KL (1999) Macroscale and microscale organic experiments, 3rd edn. Houghto-Mifflin, Boston, pp 426–427. ISBN 0-395-90220-7

  • World Health Organization (2012) Human African trypanosomiasis. http://www.who.int/trypanosomiasis_african/en/. Accessed 13 May 2012

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Acknowledgments

This study was possible thanks to financial and technical support of the Belgium Kingdom through the BTC that we thank very sincerely. We also thank Professor Lambert and all the staff of LDRI at the Catholic University of Louvain.

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Authors and Affiliations

  1. Laboratoire de Chimie Organique Physique et de Synthèse, Faculté des Sciences et Techniques, Université d’Abomey-Calavi, Cotonou, BP 4521, Republic of Benin

    Houssou Raymond Fatondji, Salomé Kpoviessi & Georges Coffi Accrombessi

  2. Laboratoire National de Pharmacognosie/Centre Béninois de la Recherche Scientifique et Technique, CBRST, Bp 06 Oganla, Porto-Novo, Republic of Benin

    Fernand Gbaguidi & Mansourou Moudachirou

  3. Louvain Drug Research Institute, LDRI, Université catholique de Louvain, B1 7203, Av. E. Mounier 72, 1200, Brussels, Belgium

    Joanne Bero, Joëlle Quetin-Leclercq & Jacques Poupaert

  4. Institut de Pathologie Cellulaire Christian Duve, ICP, 73.30, 1200, Brussels, Belgium

    Veronique Hannaert

Authors
  1. Houssou Raymond Fatondji
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  2. Salomé Kpoviessi
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  3. Fernand Gbaguidi
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  4. Joanne Bero
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  6. Joëlle Quetin-Leclercq
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  8. Mansourou Moudachirou
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  9. Georges Coffi Accrombessi
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Corresponding author

Correspondence to Salomé Kpoviessi.

Appendix: Spectral data of thiosemicarbazones

Appendix: Spectral data of thiosemicarbazones

Acetophenone-thiosemicarbazone (1)

IR ν (KBr cm−1): 3408, 3233, 3145 (NH), 1587 (C=N).

1H NMR δ (CDCl3 ppm): 2.3 (3H, s, CH3), 7.39–7.52 (several signals: 5H of ArH and 1H of NH2), 6.54 (1H, s, NH2); 8.87 (1H, s, NH).

13C NMR δ (DMSO-d 6 ppm): 12.28 (CH3) from 124.31 to 135.24 (Aromatic C), 146.75 (C=N), 177.21 (C=S).

4-Methoxyacetophenone-thiosemicarbazone (2)

IR ν (KBr cm−1): 3400, 3247, 3162 (NH), 1588 (C=N).

1H NMR δ (DMSO-d 6 ppm): 2.26 (3H, s, CH3), 3.78 (3H, s, O–CH3), 7.39–7.52 (several signals, 4H of ArH and 1H of NH2) 8.19 (1H, s, NH2) 10.10 (1H, s, NH).

13C NMR δ (DMSO-d 6 ppm): 13.24 (CH3) 54.59 (O–CH3) from 112.94 to 129.45 and 159.61 (Aromatic C), 147.21 (C=N), 178.02 (C=S).

3′,4′-Dimethoxyacetophenone-thiosemicarbazone (3)

IR ν (KBr cm−1): 3376, 3267, 3155 (NH), 1588 (C=N).

1H NMR δ (DMSO-d 6 ppm): 2.27 (3H, s, CH3), 3.78 (3H, s, O–CH3), 3.82 (3H, s, O–CH3), 6.92–7.51 (3H, several signals, ArH), 7.88 (1H, s, NH2), 8.22 (1H, s, NH2), 10.06 (1H, s, NH).

13C NMR δ (DMSO-d 6 ppm): 12.95 (CH3) 54.45 (O–CH3) 54.65 (O–CH3) from 108.60 to 129.19 and 149.12, 147.49 (Aromatic C), 147.19 (C=N), 177.52 (C=S).

2′,3′,4′-Trimethoxyacetophenone-thiosemicarbazone (4)

IR ν (KBr cm−1): 3341, 3264, 3173 (NH), 1585 (C=N).

1H NMR δ (DMSO-d 6 ppm): 2.30 (3H, s, CH3), 3.68 (3H, s, O–CH3), 3.84 (6H, s, 2-OCH3) 7, 12 (2H, s, ArH), 7.92 (1H, s, NH2), 8.27 (1H, s, NH2), 10.10 (1H, s, NH).

13C NMR δ (DMSO-d 6 ppm): 12.25 (CH3) 53.98 (2 O–CH3) 57.91 (O–CH3), 102.24 to 136.70 and 150.51 (Aromatic C), 146.12 (C=N), 176.60 (C=S).

2′-Chloroacetophenone-thiosemicarbazone (5)

IR ν (KBr cm−1): 3400, 3138 (NH), 1587 (C=N).

1H NMR δ (DMSO-d 6 ppm): 2.28 (3H, s, CH3), 7.38–7.49 (4H, several signals, ArH), 7.62 (1H, s, NH2) 8, 24 (1H, s, NH2), 10.34 (1H, s, NH).

13C NMR δ (DMSO-d 6 ppm): 18.46 (CH3) 127–138 (Aromatic C), 148.44 (C=N), 179.21 (C=S).

4′-Chloroacetophenone-thiosemicarbazone (6)

IR ν (KBr cm−1): 3418, 3139 (NH), 1587 (C=N, C=C).

1H NMR δ (DMSO-d 6 ppm): 2.29 (3H, s, CH3), 7.41–7.96 (4H, several signals, ArH), 8.00 (1H, s, NH2) 8, 32 (1H, s, NH2), 10.26 (1H, s, NH).

13C NMR δ (DMSO-d 6 ppm): 14.12 (CH3) from 128.42 to 136.74 (Aromatic C), 146.80 (C=N), 179.25 (C=S).

3′-Bromoacetophenone-thiosemicarbazone (7)

IR ν (KBr cm−1): 3392, 3212, 3144 (NH), 1588 (C=N, C=C).

1H NMR δ (DMSO-d 6 ppm): 2.28 (3H, s, CH3), 7.34–7.90 and 8.19 (4H, several signals, ArH), 8.11 (1H, s, NH2), 8.32 (1H, s, NH2), 10.25 (1H, s, NH).

13C NMR δ (DMSO-d 6 ppm): 13.93 (CH3) from 122.01 to 140.01 (Aromatic C), 146.27 (C=N), 179.01 (C=S).

4′-Bromoacetophenone-thiosemicarbazone (8)

IR ν (KBr cm−1): 3410, 3193, 3140 (NH), 1587 (C=N, C=C).

1H NMR δ (DMSO-d 6 ppm): 2.28 (1H, s, CH3), 7.54–7.90 (4H, several signals, ArH), 8.00 (1H, s, NH2) 8, 32 (1H, s, NH2), 10.33 (1H, s, NH). 13C NMR δ (DMSO-d 6 ppm): 13.79 (CH3) from 122.68 to 136.83 and 146.59 (Aromatic C), 142.12 (C=N), 178.96 (C=S).

Acetonaphthone-thiosemicarbazone (9)

IR ν (KBr cm−1): 3435, 3193 (NH), 1606 (C=N).

1H NMR δ (DMSO-d 6 ppm): 2.4 (3H, s, CH3), 7.54–7.88 (7H, several signals, ArH), 8.00 (1H, s, NH2) 8, 38 (1H, s, NH2), 10.30 (1H, s, NH).

13C NMR δ (DMSO-d 6 ppm): 11.89 (CH3) from 122.18 to 133.19 (Aromatic C), 145.71 (C=N), 177.05 (C=S).

Benzaldehyde-thiosemicarbazone (10)

IR ν (KBr cm−1): 3401, 3145 (NH), 1600, 1584 (C=N).

1H NMR δ (DMSO-d 6 ppm): 7.39–7.79 (5H, several signals, ArH), 8.00 (1H, s, NH2), 8.06 (1H, s, CH=N); 8.21 (1H, s, NH2), 11.44 (1H, s, NH).

13C NMR δ (DMSO-d 6 ppm): 127.26–134.15 (Aromatic C), 142.24 (C=N), 177.97 (C=S).

2′-Chlorobenzaldehyde-thiosemicarbazone (11)

IR ν (KBr cm−1): 3416, 3154 (NH), 1593 (C=N, C=C).

1H NMR δ (DMSO-d 6 ppm): 7.35–7.42 and 8.28 (4H, several signals, ArH), 8.11 (1H, s, NH2), 8.31 (1H, s, NH2), 8.47 (1H, s, CH=N), 11.62 (1H, s, NH). 13C NMR δ (DMSO-d 6 ppm): 127.28–133.09 (Aromatic C), 138.11 (C=N), 178.21 (C=S).

3′-Thiosemicarbazone-chlorobenzaldehyde (12)

IR ν (KBr cm−1): 3392, 3233, 3156 (NH), 1532 (C=N, C=C).

1H NMR δ (DMSO-d 6 ppm): 7.41–7.90 (4H, several signals, ArH), 7.93 (1H, s, CH=N), 8.19 (1H, s, NH2); 8.26 (1H, s, NH2), 11.51 (1H, s, NH).

13C NMR δ (DMSO-d 6 ppm): 125.98–136.45 (Aromatic C), 140.48 (C=N), 178.17 (C=S).

4′-Chlorobenzaldehyde-thiosemicarbazone (13)

IR ν (KBr cm−1): 3437, 3281, 3165 ν (NH), 1600, 1525 (C=N).

1H NMR δ (DMSO-d 6 ppm): 7.43–7.84 (4H, several signals, ArH), 8.03 (1H, s, CH=N), 8.07 (1H, s, NH2); 8.24 (1H, s, NH), 11.49 (1H, s, NH).

13C NMR δ (DMSO-d 6 ppm): 128.65–134.22 (Aromatic C), 140.85 (C=N), 178.06 (C=S).

3′-Thiosemicarbazone-methoxybenzaldehyde (14)

IR ν (KBr cm−1): 3396, 3279, 3155 (NH), 1576 (C=N, C=C).

1H NMR δ (DMSO-d 6 ppm): 3.80 (1H, s, OCH3), 6.94–7.44 (4H, several signals, ArH), 8.02 (1H, s, CH=N); 8.06 (1H, s, NH2), 8.22 (1H, s, NH2), 11.43 (1H, s, NH).

13C NMR δ (DMSO-d 6 ppm): 55.25 (OCH3), 110.91–135.57 and 159.54 (Aromatic C), 142.12 (C=N), 177.94 (C=S).

4′-Methoxybenzaldehyde-thiosemicarbazone (15)

IR ν (KBr cm−1): 3404, 3290 (NH), 1599, 1537 (C=N).

1H NMR δ (DMSO-d 6 ppm): 3.78 (3H, s, O–CH3) 6.94–7.74 (4H, several signals, ArH), 7.91 (1H, s, NH2) 8, 01 (1H, s, CH=N), 8.11 (1H, s, NH), 11.32 (1H, s, NH).

13C NMR δ (DMSO-d 6 ppm): 55.91 (OCH3), 113.29–128.87 and 160.65 (Aromatic C), 142.23 (C=N), 177.59 (C=S).

Methoxypropiophenone-4′-thiosemicarbazone (16)

IR ν (KBr cm−1): 3433, 3278 (NH), 1596 (C=N).

1H NMR δ (DMSO-d 6 ppm): 1.01 (3H, t, CH3), 2.83 (2H, q, CH2), 3.78 (3H, s, O–CH3), 6.92–7.87 (4H, several signals, ArH), 7.85 (1H, s, NH2), 8.18 (1H, s, NH2), 10.19 (1H, s, NH).

13C NMR δ (DMSO-d 6 ppm): 11.01 (CH3) 19.11 (CH2) 55.17 (O–CH3) from 112.96 to 128.06 and 160.17 (Aromatic C) 151, 78 (C=N), 178.70 (C=S).

4′-Methylbenzaldehyde-thiosemicarbazone (17)

IR ν (KBr cm−1): 3402, 3239, 3156 (NH), 1598 (C=N).

1H NMR δ (DMSO-d 6 ppm): 2.31 (1H, s, CH3), 7.19–7.68 (4H, several signals, ArH), 8.03 (1H, s, CH=N); 7.94 (1H, s, NH2), 8.18 (1H, s, NH2), 11.38 (1H, s, NH).

13C NMR δ (DMSO-d 6 ppm): 18.83 (CH3) from 124.79 to 137.15 (Aromatic C), 139.92 (C=N), 175.36 (C=S).

2′-Methylbenzaldehyde-thiosemicarbazone (18)

IR ν (KBr cm−1): 3420, 3257, 3156 (NH), 1592 (C=N, C=C).

1H NMR δ (DMSO-d 6 ppm): 2.34 (1H, s, CH3), 7.19–7.26 and 8.03 (4H, several signals, ArH), 7.83 (1H, s, NH2), 8.19 (1H, s, NH2), 8.40 (1H, s, CH=N), 11.34 (1H, s, NH).

13CNMR δ (DMSO-d 6 ppm): 18.83 (CH3) from 125.96 to 136.75 and 159.54 (Aromatic C), 141.08 (C=N), 177.82 (C=S).

2′-Nitrobenzaldehyde-thiosemicarbazone (19)

IR ν (KBr cm−1): 3424, 3245, 3159 ν (NH), 1539 (C=N, C=C).

1H NMR δ (DMSO-d 6 ppm): 7.63–8.02 and 8.41 (4H, several signals, ArH), 8.11 (1H, s, NH2), 8.39 (1H, s, NH2), 8.47 (1H, s, CH=N), 11.74 (1H, s, NH). 13C NMR δ (DMSO-d 6 ppm): 124.44–137.19 (Aromatic C), 148.22 (C=N), 178.45 (C=S).

3′-Thiosemicarbazone-nitrobenzaldehyde (20)

IR ν (KBr cm−1): 3395, 3242, 3157 (NH), 1604, 1526 (C=N).

1H NMR δ (DMSO-d 6 ppm): 7.65–8.24 (4H, several signals, ArH), 8.33 (1H, s, NH2), 8.30 (1H, s, CH=N); 8.63 (1H, s, NH2), 11.61 (1H, s, NH).

13C NMR δ (DMSO-d 6 ppm): 121.32–139.88 (Aromatic C), 148.33 (C=N), 178.31 (C=S).

2′-Hydroxybenzaldehyde-thiosemicarbazone (21)

IR ν (KBr cm−1): 3443, 3319, 3172 ν (NH), 1539 ν (C=N).

1H NMR δ (DMSO-d 6 ppm): 6.79–7.90 (4H, several signals, ArH), 7.67 (1H, s, NH2), 7.92 (1H, s, NH2) 8, 37 (1H, s, CH=N), 9.86 (OH) 11.37 (1H, s, NH). 13CNMR δ (DMSO-d 6 ppm): 114.91–155.28 (Aromatic C), 138.50 (C=N), 176.55 (C=S).

4′-Hydroxy-3′-thiosemicarbazone-methoxybenzaldehyde (22)

IR ν (KBr cm−1): 3528 (OH), 3437, 3276, 3154 (NH), 1587 (C=N).

1H NMR δ (DMSO-d 6 ppm): 3.83 (3H, s, CH3), 6.79–7.32 (3H, several signals, ArH), 7.95 (1H, s, CH=N); 7.93 (1H, s, NH2), 8.08 (1H, s, NH2), 9.41 (1H, s, OH), 11.23 (1H, s, NH).

13C NMR δ (DMSO-d 6 ppm): 55.74 (O–CH3) from 109.31 to 140.77 and 148.06 (Aromatic C), 142.89 (C=N), 177.38 (C=S).

5′-Chloro-2′-hydroxybenzaldehyde-thiosemicarbazone (23)

IR ν (KBr cm−1): 3405, 3236, 3165 ν (NH), 1598, 1565 ν (C=N).

1H NMR δ (DMSO-d 6 ppm): 6.86–8.08 (3H, several signals, ArH), 8.15 (2H, s, NH2), 8.31 (1H, s, CH=N); 10.18 (1H, s, OH), 11.42 (1H, s, NH).

13C NMR δ (DMSO-d 6 ppm): 117.64–130.33 and 155.09 (Aromatic C), 137.37 (C=N), 177.83 (C=S).

Cyclohexanone thiosemicarbazone (24)

IR ν (KBr cm−1): 3379, 3215, 3144 (NH), 1585 (C=N).

1H NMR δ (DMSO-d 6 ppm): 1.54–2.39 (10H, several signals, CH2 hexane), 7.50 (1H, s, NH2), 7.95 (1H, s, NH2) 10, 13 (1H, s, NH).

13C NMR δ (DMSO-d 6 ppm): 25.01–34.87 (cyclohexane CH2), 156.94 (C=N), 178.49 (C=S).

Carvone-thiosemicarbazone (25)

IR ν (KBr cm−1): 3415, 3259 (NH), 1598 (C=N).

1H NMR δ (DMSO-d 6 ppm): 1.82 (3H, s, CH3), 1.9 (3H, s, CH3) 2, 28 (4H, m, 2CH2), 2.68 (1H, q, CH2–CH2–CH), 4.8 (2H, s, =CH2), 5.1 (1H, t, CH=C), 6.3 (1H, s, NH2), 7.81 (1H, s, NH2) 10.3 (1H, s, NH).

13C NMR δ (DMSO-d 6 ppm): 19–22 (CH3) 29–42 (CH2 CH and carvone) 109–150 (=CH and =CH2), 148.29 (C=N), 176.16 (C=S).

Methyladamantylcetone-1-thiosemicarbazone (26)

1H NMR δ (DMSO-d 6 ppm): 1.62–1.71 (15H, several signals, CH and CH2), 1.98 (3H, s, CH3), 7.30 (1H, s, NH2); 8.10 (1H, s, NH2), 8.31 (1H, s, CH=N), 9.80 (1H, s, NH).

13C NMR δ (DMSO-d 6 ppm): 11.51 (CH3) 27.61–36.17 (several signals CH and CH2) 159.52 (C=N), 178.80 (C=S).

Cinnamaldehyde thiosemicarbazone (27)

IR ν (KBr cm−1): 3418, 3259, 3156 (NH), 1592 (C=N).

1H NMR δ (DMSO-d 6 ppm): 6.83–7.02 (2H, several signals, CH=CH), 7.29–7.55 (5H, several signals, ArH), 7.91 (1H, d, CH=N), 7.62 (1H, s, NH2), 8.18 (1H, s, NH2), 11.41 (1H, s, NH).

13C NMR δ (DMSO-d 6 ppm): 125.02–140.84 (Aromatic C and CH=CH), 144.72 (C=N), 177.67 (C=S).

4′-(N,N-dimethylamino)-cinnamaldehyde thiosemicarbazone (29)

IR (KBr cm−1): 3408, 3245, 3140 ν (NH), 1598 ν (C=N).

1H NMR δ (DMSO-d 6 ppm): 2.94 (6H, s, CH3–N–CH3), 6.54–7.38 (6H, several signals, CH=CH and ArH), 7.51 (1H, s, NH2), 7.85 (1H, d, CH=N), 8.05 (1H, s, NH2), 11.24 (1H, s, NH).

13C NMR δ (DMSO-d 6 ppm): 40.14 (CH3–N–CH3) from 112.00 to 139.81 and 150.66 (Aromatic C), 145.88 (C=N), 177.12 (C=S).

3′-Bromobenzaldehyde-thiosemicarbazone (30)

IR ν (KBr cm−1): 3391, 3235, 3155 (NH), 1602, 1532 (C=N).

1H NMR δ (DMSO-d 6 ppm): 7.22–7.48 and 7.74 (4H, several signals, ArH), 7.79 (1H, s, CH=N), 7.84 (1H, s, NH2), 7.87 (1H, s, NH2), 11.51 (1H, s, NH). 13CNMR δ (DMSO-d 6 ppm): 122.33–136.65 (Aromatic C), 140.43 (C=N), 178.15 (C=S).

Benzophenone-thiosemicarbazone (31)

IR ν (KBr cm−1): 3412, 3248, 3153 (NH), 1609 (C=N).

1H NMR δ (DMSO-d 6 ppm): 7.35–7.47 (10H, several signals, ArH), 7.86 (1H, s, NH2), 7.87 (1H, s, NH2) 8, 65 (1H, s, NH).

13C NMR δ (DMSO-d 6 ppm): 127.55–136.29 (Aromatic C), 149.06 (C=N), 177.85 (C=S).

1,3-Diphenylacetone-thiosemicarbazone (32)

IR ν (KBr cm−1): 3336, 3296, 3228, 3138 (NH), 1601 (C=N).

1H NMR δ (DMSO-d 6 ppm): 3.48 (1H, s, CH2), 3.75 (1H, s, CH2), 7.12–7.25 (10H, several signals, ArH), 7, 43 (1H, s, NH2), 8.21 (1H, s, NH2), 10.43 (1H, s, NH).

13C NMR δ (DMSO-d 6 ppm): 34.41 (CH2) 42.35 (CH2) 126.53–137.04 (Aromatic C), 152.36 (C=N), 179.03 (C=S).

1-(1-(Naphth-2-yl) ethylidene)-4-phenylthiosemicarbazide (33)

IR ν (KBr cm−1): 3303, 3237 (NH), 1589, 1520 (C=N).

1H NMR δ (DMSO-d 6 ppm): 2.53 (3H, s, CH3), 7.24–8.28 (12H, several signals, ArH), 10.17 (1H, s, NH-ArH); 10.82 (1H, s, NH).

13C NMR δ (DMSO-d 6 ppm): 14.25 (CH3) from 124.77 to 139.22 (Aromatic C), 148.77 (C=N), 177.10 (C=S).

1-(4-Chlorophenyl) ethylidene-4-phenyl-thiosemicarbazide (34)

IR ν (KBr cm−1): 3303, 3256 (NH), 1590, 1520 (C=N).

1H NMR δ (DMSO-d 6 ppm): 2.39 (3H, s, CH3), 7.23–8.07 (9H, several signals, ArH), 10.10 (1H, s, NH-ArH); 10.65 (1H, s, NH).

13C NMR δ (DMSO-d 6 ppm): 14.22 (CH3) from 125.36 to 139.40 (Aromatic C), 147.54 (C=N), 177.07 (C=S).

1-(4-Bromophenyl) ethylidene-4-phenyl-thiosemicarbazide (35)

IR ν (KBr cm−1): 3303, 3225 (NH), 1587, 1518 (C=N).

1H NMR δ (DMSO-d 6 ppm): 2.38 (3H, s, CH3), 7.22–7.90 (9H, several signals, ArH), 10.10 (1H, s, NH-ArH); 10.65 (1H, s, NH).

13C NMR δ (DMSO-d 6 ppm): 14.23 (CH3) from 122.93 to 139.13 (Aromatic C), 147.67 (C=N), 177.01(C=S).

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Fatondji, H.R., Kpoviessi, S., Gbaguidi, F. et al. Structure–activity relationship study of thiosemicarbazones on an African trypanosome: Trypanosoma brucei brucei . Med Chem Res 22, 2151–2162 (2013). https://doi.org/10.1007/s00044-012-0208-6

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  • DOI: https://doi.org/10.1007/s00044-012-0208-6

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