Gold(I) and Silver(I) Complexes Containing Hybrid Sulfonamide/Thiourea Ligands as Potential Leishmanicidal Agents
Alice P. Borges,
Malu M. S. Obata,
Silvia H. Libardi,
Rafael O. Trevisan,
Victor M. Deflon,
Ulrich Abram,
Francis B. Ferreira,
Luiz Antônio S. Costa,
Antonio O. T. Patrocínio,
Marcos V. da Silva,
Júlio C. Borges,
Pedro I. S. Maia
Affiliations
Alice P. Borges
Bioactive Compounds Development Research Group, Federal University of Triângulo Mineiro, Av. Dr. Randolfo Borges 1400, Uberaba 38025-440, MG, Brazil
Malu M. S. Obata
Department of Microbiology, Immunology and Parasitology, Federal University of Triângulo Mineiro, Av. Getúlio Guarita, Uberaba 38025-440, MG, Brazil
Silvia H. Libardi
São Carlos Institute of Chemistry, University of São Paulo, Av. Trabalhador São Carlense, 400, São Carlos 13566-590, SP, Brazil
Rafael O. Trevisan
Department of Microbiology, Immunology and Parasitology, Federal University of Triângulo Mineiro, Av. Getúlio Guarita, Uberaba 38025-440, MG, Brazil
Victor M. Deflon
São Carlos Institute of Chemistry, University of São Paulo, Av. Trabalhador São Carlense, 400, São Carlos 13566-590, SP, Brazil
Ulrich Abram
Institute of Chemistry and Biochemistry, Freie Universität Berlin, Fabeckstr. 34/36, 14195 Berlin, Germany
Francis B. Ferreira
Associated Faculties of Uberaba, Av. do Tutuna 720, Uberaba 38061-500, MG, Brazil
Luiz Antônio S. Costa
Computational Chemistry Research Group, Institute of Exact Sciences, Federal University of Juiz de Fora, Campus Universitário s/n Martelos, Juiz de Fora 36036-900, MG, Brazil
Antonio O. T. Patrocínio
Laboratory of Photochemistry and Material Science, Institute of Chemistry, Federal University of Uberlândia, Av. João Naves de Ávila 2121, Uberlândia 38400-902, MG, Brazil
Marcos V. da Silva
Department of Microbiology, Immunology and Parasitology, Federal University of Triângulo Mineiro, Av. Getúlio Guarita, Uberaba 38025-440, MG, Brazil
Júlio C. Borges
São Carlos Institute of Chemistry, University of São Paulo, Av. Trabalhador São Carlense, 400, São Carlos 13566-590, SP, Brazil
Pedro I. S. Maia
Bioactive Compounds Development Research Group, Federal University of Triângulo Mineiro, Av. Dr. Randolfo Borges 1400, Uberaba 38025-440, MG, Brazil
Leishmaniasis is a group of parasitic diseases with the potential to infect more than 1 billion people; however, its treatment is still old and inadequate. In order to contribute to changing this view, this work consisted of the development of complexes derived from MI metal ions with thioureas, aiming to obtain potential leishmanicidal agents. The thiourea ligands (HLR) were obtained by reactions of p-toluenesulfohydrazide with R-isothiocyanates and were used in complexation reactions with AgI and AuI, leading to the formation of complexes of composition [M(HLR)2]X (M = Ag or Au; X = NO3− or Cl−). All compounds were characterized by FTIR, 1H NMR, UV-vis, emission spectroscopy and elemental analysis. Some representatives were additionally studied by ESI-MS and single-crystal XRD. Their properties were further analyzed by DFT calculations. Their cytotoxicity on Vero cells and the extracellular leishmanicidal activity on Leishmania infantum and Leishmania braziliensis cells were evaluated. Additionally, the interaction of the complexes with the Old Yellow enzyme of the L. braziliensis (LbOYE) was examined. The biological tests showed that some compounds present remarkable leishmanicidal activity, even higher than that of the standard drug Glucantime, with different selectivity for the two species of Leishmania. Finally, the interaction studies with LbOYE revealed that this enzyme could be one of their biological targets.
