title: Gold(III) complexes with ONS-Tridentate thiosemicarbazones: Toward selective trypanocidal drugs.
abstract: Tridentate thiosemicarbazone ligands with an ONS donor set, H2L(R) (R = Me and Et) were prepared by reactions of 1-phenyl-1,3-butanedione with 4-R-3-thiosemicarbazides. H2L(R) reacts with Na[AuCl4]·2H2O in MeOH in a 1:1 M ratio under formation of green gold(III) complexes of composition [AuCl(L(R))]. These compounds represent the first examples of gold(III) complexes with ONS chelate-bonded thiosemicarbazones. The in vitro anti-Trypanosoma cruzi activity against both trypomastigote and amastigote forms (IC50try/ama) of CL Brener strains as well as the cytotoxicity against LLC-MK2 cells of the free ligands and complexes was evaluated. The complex [AuCl(L(Me))] was found to be more active and more selective than its precursor ligand and the standard drug benznidazole with a SItry/ama value higher than 200, being considered as a lead candidate for Chagas disease treatment. Moreover the in vitro activity against the replicative amastigote form (IC50ama) of T. cruzi was additionally investigated revealing that [AuCl(L(Me))] was also more potent than benznidazole still with a similar selectivity index. Finally, docking studies showed that free ligands and complexes interact with the same residues of the parasite protease cruzain but with different intensities, suggesting that this protease could be a possible target for the trypanocidal action of the obtained compounds.
authors.affiliation: Departamento de Química, Universidade Federal do Triângulo Mineiro, Av. Dr. Randolfo Borges 1400, 38025-440, Uberaba, MG, Brazil.
authors.forename: Andressa R
authors.initials: AR
authors.lastname: Rettondin
authors.affiliation: 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.
authors.forename: Zumira A
authors.initials: ZA
authors.lastname: Carneiro
authors.affiliation: Departamento de Química, Universidade Federal do Triângulo Mineiro, Av. Dr. Randolfo Borges 1400, 38025-440, Uberaba, MG, Brazil.
authors.forename: Ana C R
authors.initials: AC
authors.lastname: Gonçalves
authors.affiliation: Instituto de Química de São Carlos, Universidade de São Paulo, Av. Trabalhador São Carlense, 400, 13566-590, São Carlos, SP, Brazil.
authors.forename: Vanessa F
authors.initials: VF
authors.lastname: Ferreira
authors.affiliation: Instituto de Química de São Carlos, Universidade de São Paulo, Av. Trabalhador São Carlense, 400, 13566-590, São Carlos, SP, Brazil.
authors.forename: Carolina G
authors.initials: CG
authors.lastname: Oliveira
authors.affiliation: Laboratório de Biofísica Teórica, Departamento de Física, Universidade Federal do Triângulo Mineiro, Av. Dr. Randolfo Borges 1400, 38025-440, Uberaba, MG, Brazil.
authors.forename: Angélica N
authors.initials: AN
authors.lastname: Lima
authors.affiliation: Laboratório de Biofísica Teórica, Departamento de Física, Universidade Federal do Triângulo Mineiro, Av. Dr. Randolfo Borges 1400, 38025-440, Uberaba, MG, Brazil.
authors.forename: Ronaldo J
authors.initials: RJ
authors.lastname: Oliveira
authors.affiliation: 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.
authors.forename: Sérgio
authors.initials: S
authors.lastname: de Albuquerque
authors.affiliation: Instituto de Química de São Carlos, Universidade de São Paulo, Av. Trabalhador São Carlense, 400, 13566-590, São Carlos, SP, Brazil.
authors.forename: Victor M
authors.initials: VM
authors.lastname: Deflon
authors.affiliation: Departamento de Química, Universidade Federal do Triângulo Mineiro, Av. Dr. Randolfo Borges 1400, 38025-440, Uberaba, MG, Brazil. Electronic address: pedro.maia@pq.cnpq.br.
authors.forename: Pedro I S
authors.initials: PI
authors.lastname: Maia
mesh_terms: D000818:Animals; D014355:Chagas Disease / Q000188:drug therapy; D056831:Coordination Complexes / Q000737:chemistry / Q000494:pharmacology*; D006046:Gold / Q000737:chemistry*; D062105:Molecular Docking Simulation; D013329:Structure-Activity Relationship; D013882:Thiosemicarbazones / Q000737:chemistry / Q000494:pharmacology*; D014344:Trypanocidal Agents / Q000737:chemistry* / Q000494:pharmacology; D014349:Trypanosoma cruzi / Q000187:drug effects
chemical_list: D056831:Coordination Complexes; D013882:Thiosemicarbazones; D014344:Trypanocidal Agents; D006046:Gold
keywords: Chagas disease; Cruzain; Gold(III) complexes; Thiosemicarbazones; Trypanosoma cruzi