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Gold(I) and Silver(I) Complexes Containing Hybrid Sulfonamide/Thiourea Ligands as Potential Leishmanicidal Agents

Affiliation
Bioactive Compounds Development Research Group, Federal University of Triângulo Mineiro, Av. Dr. Randolfo Borges 1400, Uberaba 38025-440, MG, Brazil;
Borges, Alice P.;
ORCID
0000-0002-6849-1702
Affiliation
Department of Microbiology, Immunology and Parasitology, Federal University of Triângulo Mineiro, Av. Getúlio Guarita, Uberaba 38025-440, MG, Brazil;(M.M.S.O.);(R.O.T.);(M.V.d.S.)
Obata, Malu M. S.;
Affiliation
São Carlos Institute of Chemistry, University of São Paulo, Av. Trabalhador São Carlense, 400, São Carlos 13566-590, SP, Brazil;(S.H.L.);(V.M.D.);(J.C.B.)
Libardi, Silvia H.;
Affiliation
Department of Microbiology, Immunology and Parasitology, Federal University of Triângulo Mineiro, Av. Getúlio Guarita, Uberaba 38025-440, MG, Brazil;(M.M.S.O.);(R.O.T.);(M.V.d.S.)
Trevisan, Rafael O.;
Affiliation
São Carlos Institute of Chemistry, University of São Paulo, Av. Trabalhador São Carlense, 400, São Carlos 13566-590, SP, Brazil;(S.H.L.);(V.M.D.);(J.C.B.)
Deflon, Victor M.;
ORCID
0000-0002-1747-7927
Affiliation
Institute of Chemistry and Biochemistry, Freie Universität Berlin, Fabeckstr. 34/36, 14195 Berlin, Germany;
Abram, Ulrich;
Affiliation
Associated Faculties of Uberaba, Av. do Tutuna 720, Uberaba 38061-500, MG, Brazil;
Ferreira, Francis B.;
ORCID
0000-0002-8544-2910
Affiliation
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;
Costa, Luiz Antônio S.;
ORCID
0000-0003-3141-3214
Affiliation
Laboratory of Photochemistry and Material Science, Institute of Chemistry, Federal University of Uberlândia, Av. João Naves de Ávila 2121, Uberlândia 38400-902, MG, Brazil;
Patrocínio, Antonio O. T.;
ORCID
0000-0002-2966-7621
Affiliation
Department of Microbiology, Immunology and Parasitology, Federal University of Triângulo Mineiro, Av. Getúlio Guarita, Uberaba 38025-440, MG, Brazil;(M.M.S.O.);(R.O.T.);(M.V.d.S.)
da Silva, Marcos V.;
ORCID
0000-0003-4856-748X
Affiliation
São Carlos Institute of Chemistry, University of São Paulo, Av. Trabalhador São Carlense, 400, São Carlos 13566-590, SP, Brazil;(S.H.L.);(V.M.D.);(J.C.B.)
Borges, Júlio C.;
ORCID
0000-0003-4699-9481
Affiliation
Bioactive Compounds Development Research Group, Federal University of Triângulo Mineiro, Av. Dr. Randolfo Borges 1400, Uberaba 38025-440, MG, Brazil;
Maia, Pedro I. S.

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 M I metal ions with thioureas, aiming to obtain potential leishmanicidal agents. The thiourea ligands (HL R ) were obtained by reactions of p -toluenesulfohydrazide with R-isothiocyanates and were used in complexation reactions with Ag I and Au I , leading to the formation of complexes of composition [M(HL R ) 2 ]X (M = Ag or Au; X = NO 3 − or Cl − ). All compounds were characterized by FTIR, 1 H 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.

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