Novel gold(I) complexes with 5-phenyl-1,3,4-oxadiazole-2-thione and phosphine as potential anticancer and antileishmanial agents.

Autor: Chaves JDS; Departamento de Química, ICE, Universidade Federal de Juiz de Fora, 36036-330, Juiz de Fora, MG, Brazil., Tunes LG; Centro de Pesquisas René Rachou - Fundação Oswaldo Cruz, 30190-002, Belo Horizonte, MG, Brazil., de J Franco CH; Departamento de Química, ICE, Universidade Federal de Juiz de Fora, 36036-330, Juiz de Fora, MG, Brazil., Francisco TM; Departamento de Física, Universidade Federal de Minas Gerais, 31270-901, Belo Horizonte, MG, Brazil., Corrêa CC; Departamento de Química, ICE, Universidade Federal de Juiz de Fora, 36036-330, Juiz de Fora, MG, Brazil., Murta SMF; Centro de Pesquisas René Rachou - Fundação Oswaldo Cruz, 30190-002, Belo Horizonte, MG, Brazil., Monte-Neto RL; Centro de Pesquisas René Rachou - Fundação Oswaldo Cruz, 30190-002, Belo Horizonte, MG, Brazil., Silva H; Departamento de Química, Universidade Federal de Minas Gerais, 31270-901, Belo Horizonte, MG, Brazil., Fontes APS; Departamento de Química, ICE, Universidade Federal de Juiz de Fora, 36036-330, Juiz de Fora, MG, Brazil., de Almeida MV; Departamento de Química, ICE, Universidade Federal de Juiz de Fora, 36036-330, Juiz de Fora, MG, Brazil. Electronic address: mauro.almeida@ufjf.edu.br.
Jazyk: angličtina
Zdroj: European journal of medicinal chemistry [Eur J Med Chem] 2017 Feb 15; Vol. 127, pp. 727-739. Date of Electronic Publication: 2016 Oct 24.
DOI: 10.1016/j.ejmech.2016.10.052
Abstrakt: The current anticancer and antileishmanial drug arsenal presents several limitations concerning their specificity, efficacy, costs and the emergence of drug-resistant cells lines, which encourages the urgent need to search for new alternatives. Inspired by the fact that gold(I)-based compounds are promising antitumoral and antileishmanial drug candidates, we synthesized novel gold(I) complexes containing phosphine and 5-phenyl-1,3,4-oxadiazole-2-thione and evaluated their anticancer and antileishmanial activities. Synthesis was performed by reacting 5-phenyl-1,3,4-oxadiazole-2-thione derivatives with chloro(triphenylphosphine)gold(I) and chloro(triethylphosphine)gold(I). The novel compounds were characterized by infrared, Raman, 1 H, 13 C nuclear magnetic resonance, high-resolution mass spectra, and x-ray crystallography. The coordination of the ligands to gold(I) occurred through the exocyclic sulfur atom. All gold(I) complexes were active at low micromolar or nanomolar range with IC 50 values ranging from <0.10 to 1.66 μM against cancer cell lines and from 0.9 to 4.2 μM for Leishmania infantum intracellular amastigotes. Compound (6-A) was very selective against murine melanoma B16F10, colon cancer CT26.WT cell lines and L. infantum intracellular amastigotes. Compound (7-B) presented the highest anticancer activity against both cancer cell lines while the promising antileishmanial lead was compound (6-A). Tiethylphosphine gold(I) complexes were more active than the conterparts triphenylphosphine derivatives for both anticancer and antileishmanial activities. Triethylphosphine gold(I) derivatives presented antimony cross-resistance in L. guyanensis demonstrating their potential to be used as chemical tools to better understand mechanisms of drug resistance and action. These findings revealed the anticancer and antileishmanial potential of gold(I) oxadiazole phosphine derivatives.
(Copyright © 2016 Elsevier Masson SAS. All rights reserved.)
Databáze: MEDLINE
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