Novel gold(I) complexes with 5-phenyl-1,3,4-oxadiazole-2-thione and phosphine as potential anticancer and antileishmanial agents.
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 IC50values 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.
Departamento de Química, ICE, Universidade Federal de Juiz de Fora, 36036-330, Juiz de Fora, MG, Brazil.
Joana Darc S
JDS
Chaves
Centro de Pesquisas René Rachou - Fundação Oswaldo Cruz, 30190-002, Belo Horizonte, MG, Brazil.
Luiza Guimarães
LG
Tunes
Departamento de Química, ICE, Universidade Federal de Juiz de Fora, 36036-330, Juiz de Fora, MG, Brazil.
Chris Hebert
CH
de J Franco
Departamento de Física, Universidade Federal de Minas Gerais, 31270-901, Belo Horizonte, MG, Brazil.
Thiago Martins
TM
Francisco
Departamento de Química, ICE, Universidade Federal de Juiz de Fora, 36036-330, Juiz de Fora, MG, Brazil.
Charlane Cimini
CC
Corrêa
Centro de Pesquisas René Rachou - Fundação Oswaldo Cruz, 30190-002, Belo Horizonte, MG, Brazil.
Silvane M F
SMF
Murta
Centro de Pesquisas René Rachou - Fundação Oswaldo Cruz, 30190-002, Belo Horizonte, MG, Brazil.
Rubens Lima
RL
Monte-Neto
Departamento de Química, Universidade Federal de Minas Gerais, 31270-901, Belo Horizonte, MG, Brazil.
Heveline
H
Silva
Departamento de Química, ICE, Universidade Federal de Juiz de Fora, 36036-330, Juiz de Fora, MG, Brazil.
Ana Paula S
APS
Fontes
Departamento de Química, ICE, Universidade Federal de Juiz de Fora, 36036-330, Juiz de Fora, MG, Brazil. Electronic address: mauro.almeida@ufjf.edu.br.
Mauro V
MV
de Almeida
D000965:Antimony / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology; D000981:Antiprotozoal Agents / Q000737:chemistry / Q000494:pharmacology; D045744:Cell Line, Tumor; D015195:Drug Design; D004351:Drug Resistance / Q000187:drug effects; D006046:Gold / Q000737:chemistry*; D006801:Humans; D018314:Leishmania infantum / Q000187:drug effects*; D050607:Organogold Compounds / Q000737:chemistry* / Q000494:pharmacology*; D010069:Oxadiazoles / Q000737:chemistry*; D010720:Phosphines / Q000737:chemistry*
D000970:Antineoplastic Agents; D000981:Antiprotozoal Agents; D050607:Organogold Compounds; D010069:Oxadiazoles; D010720:Phosphines; C583463:1,3,4-oxadiazole; D006046:Gold; D000965:Antimony
5-Phenyl-1,3,4-oxadiazole-2-thione; Antileishmania; Antitumor activity; Gold(I) complexes