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2023-01-01
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NOVEL GOLD(I) COMPLEXES WITH 5-PHENYL-1,3,4-OXADIAZOLE-2-THIONE AND PHOSPHINE AS POTENTIAL ANTICANCER AND ANTILEISHMANIAL AGENTS
5-Phenyl-1,3,4-oxadiazole-2-thione
Antitumor activity
antileishmanicidas
Author
Affilliation
Universidade Federal de Juiz de Fora. Instituto de Ciências Exatas. Departamento de Química. Juiz de Fora, MG, Brasil.
Fundação Oswaldo Cruz. Instituto Rene Rachou. Belo Horizonte, MG, Brasil.
Universidade Federal de Juiz de Fora. Instituto de Ciências Exatas. Departamento de Química. Juiz de Fora, MG, Brasil.
Universidade Federal de Minas Gerais. Departamento de Física. Belo Horizonte, MG, Brasil.
Universidade Federal de Juiz de Fora. Instituto de Ciências Exatas. Departamento de Química. Juiz de Fora, MG, Brasil.
Fundação Oswaldo Cruz. Instituto Rene Rachou. Belo Horizonte, MG, Brasil.
Fundação Oswaldo Cruz. Instituto Rene Rachou. Belo Horizonte, MG, Brasil.
Universidade Federal de Minas Gerais. Departamento de Química. Belo Horizonte, MG, Brasil.
Universidade Federal de Juiz de Fora. Instituto de Ciências Exatas. Departamento de Química. Juiz de Fora, MG, Brasil.
Universidade Federal de Juiz de Fora. Instituto de Ciências Exatas. Departamento de Química. Juiz de Fora, MG, Brasil.
Fundação Oswaldo Cruz. Instituto Rene Rachou. Belo Horizonte, MG, Brasil.
Universidade Federal de Juiz de Fora. Instituto de Ciências Exatas. Departamento de Química. Juiz de Fora, MG, Brasil.
Universidade Federal de Minas Gerais. Departamento de Física. Belo Horizonte, MG, Brasil.
Universidade Federal de Juiz de Fora. Instituto de Ciências Exatas. Departamento de Química. Juiz de Fora, MG, Brasil.
Fundação Oswaldo Cruz. Instituto Rene Rachou. Belo Horizonte, MG, Brasil.
Fundação Oswaldo Cruz. Instituto Rene Rachou. Belo Horizonte, MG, Brasil.
Universidade Federal de Minas Gerais. Departamento de Química. Belo Horizonte, MG, Brasil.
Universidade Federal de Juiz de Fora. Instituto de Ciências Exatas. Departamento de Química. Juiz de Fora, MG, Brasil.
Universidade Federal de Juiz de Fora. Instituto de Ciências Exatas. Departamento de Química. Juiz de Fora, MG, Brasil.
Abstract
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, 1H, 13C 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 IC50 values ranging from <0.10 to 1.66 mM against cancer cell lines and from 0.9 to 4.2 mM for Leishmania infantum intra-cellular 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.
Keywords in Portuguese
Complexos de ouro (I)5-Phenyl-1,3,4-oxadiazole-2-thione
Antitumor activity
antileishmanicidas
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