Organometallic gold(iii) complexes with hybrid SNS-donating thiosemicarbazone ligands: cytotoxicity and anti-Trypanosoma cruzi activity.
Stable organogold(iii) compounds of the composition [AuIII(Hdamp)(L1)]Cl are formed from reactions of [AuCl2(damp)] with H2L1 (damp-= dimethylaminomethylphenyl; H2L1 = N'-(diethylcarbamothioyl)benzimidothiosemicarbazides). The cationic complexes can be neutralized by reactions with weak bases under the formation of [AuIII(damp)(L1)] compounds. The structures of the products show interesting features like relatively short AuH contacts between the methylene protons of the Hdamp ligand and the gold(iii) ions. Preliminary biological studies on the uncoordinated compounds H2L1 and their gold complexes indicate considerable cytotoxicity for the [AuIII(Hdamp)(L1)]Cl complexes against MCF-7 cells. The in vitro trypanocidal activity was evaluated against the intracellular form of Trypanosoma cruzi. The organometallic complexes display a remarkable activity, which is dependent on the alkyl substituents of the thiosemicarbazone building blocks of the ligands. One representative of the cationic [AuIII(Hdamp)(L1)]Cl complexes, where H2L1 contains a dimethylthiosemicarbazide building block, shows a trypanocidal activity against the intracellular amastigote form in the same order of magnitude as that of the standard drug benznidazole. Furthermore, no appreciable toxicity to mice spleen cells is observed for this compound resulting in a therapeutic index of about 30, which strongly recommends it as a promising candidate for the development of a future antiparasitic drug.
Departamento de Química, Universidade Federal do Triângulo Mineiro, 38025-440, Uberaba, MG, Brazil. pedro.maia@pq.cnpq.br.
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PI
Maia
Departamento de Análises Clínicas, Toxicológicas e Bromatológicas, Faculdade de Ciências Farmacêuticas de Ribeirão Preto - FCFRP-USP, Universidade de São Paulo, Avenida do Café s/n, 14040-903, Ribeirão Preto, SP, Brazil and Department of Biochemistry and Immunology, School of Medicine, University of São Paulo, Av. Bandeirantes 3900, 14040-900, Ribeirão Preto, SP, Brazil.
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ZA
Carneiro
Department of Biochemistry and Immunology, School of Medicine, University of São Paulo, Av. Bandeirantes 3900, 14040-900, Ribeirão Preto, SP, Brazil.
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CD
Lopes
Instituto de Química de São Carlos, Universidade de São Paulo, Av. Trabalhador São Carlense, 400, 13566-590, São Carlos, SP, Brazil.
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CG
Oliveira
Department of Biochemistry and Immunology, School of Medicine, University of São Paulo, Av. Bandeirantes 3900, 14040-900, Ribeirão Preto, SP, Brazil.
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JS
Silva
Departamento de Análises Clínicas, Toxicológicas e Bromatológicas, Faculdade de Ciências Farmacêuticas de Ribeirão Preto - FCFRP-USP, Universidade de São Paulo, Avenida do Café s/n, 14040-903, Ribeirão Preto, SP, Brazil.
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S
de Albuquerque
Freie Universität Berlin, Institute of Chemistry and Biochemistry, Fabeckstr. 34-36, D-14195 Berlin, Germany. ulrich.abram@fu-berlin.de.
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A
Hagenbach
Freie Universität Berlin, Institute of Pharmacy, Königin-Luise-Str. 2+4, 14195 Berlin, Germany.
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R
Gust
Instituto de Química de São Carlos, Universidade de São Paulo, Av. Trabalhador São Carlense, 400, 13566-590, São Carlos, SP, Brazil.
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VM
Deflon
Freie Universität Berlin, Institute of Chemistry and Biochemistry, Fabeckstr. 34-36, D-14195 Berlin, Germany. ulrich.abram@fu-berlin.de.
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http://orcid.org/0000-0002-1747-7927
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Abram
D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology; D006046:Gold / Q000737:chemistry*; D006801:Humans; D008024:Ligands; D061986:MCF-7 Cells; D008958:Models, Molecular; D008968:Molecular Conformation; D009942:Organometallic Compounds / Q000737:chemistry* / Q000494:pharmacology*; D013882:Thiosemicarbazones / Q000737:chemistry*; D014344:Trypanocidal Agents / Q000737:chemistry / Q000494:pharmacology; D014349:Trypanosoma cruzi / Q000187:drug effects*
D000970:Antineoplastic Agents; D008024:Ligands; D009942:Organometallic Compounds; D013882:Thiosemicarbazones; D014344:Trypanocidal Agents; D006046:Gold