RESUMO
Herein we report the regioselective synthesis of podophyllotoxin-Glycosyl triazole hybrids catalysed by Ag(I)-N-heterocyclic carbene (Ag(I)-NHC) in a short reaction time (â¼30 min) at ambient conditions. In principle, it is the first report of Click alkyne-azide cycloaddition catalysed by Ag(I)-NHC catalyst and moreover, this new methodology yielded good results when compared with traditional CuAAC in terms of reaction time and selectivity. The synthesised compounds were further explored for in vitro anticancer activity against four human cancer cell lines Du145, HeLa, A-549, and MCF-7 and found that these synthesised compounds possess significant anticancer activity. Further, the compounds 5a and 5e were identified as promising leads due to their better activity across all cell lines than that of the standard drug etoposide. Molecular docking studies of 5a & 5e with DNA Topoisomerase-II were revealed that the free energy calculations of active compounds were in good agreement with observed IC50 values.
Assuntos
Antineoplásicos/farmacologia , Podofilotoxina/química , Inibidores da Topoisomerase II/síntese química , Inibidores da Topoisomerase II/farmacologia , Antineoplásicos/síntese química , Antineoplásicos/química , Linhagem Celular Tumoral , Química Click , Reação de Cicloadição , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Metano/análogos & derivados , Metano/química , Simulação de Acoplamento Molecular , Prata/química , Relação Estrutura-Atividade , Inibidores da Topoisomerase II/química , Triazóis/químicaRESUMO
A new series (except compound 3a) of d-ring modified acid hydrazides of podophyllotoxin were synthesized by cleaving of its d-ring with various hydrazines. Furthermore, the synthesized compounds were screened for their anticancer activity against human tumor cell lines i.e., MCF-7, HeLa and A-549 and among the synthesized compounds 3c and 3f have shown significant anticancer activity almost similar to that of standard drug etoposide. Molecular modelling studies were also conducted for active compounds and found that the free energies obtained were in good agreement with the observed IC50 values.