RESUMO
A series of novel ß-diketo derivatives which combined the virtues of 1,3-diketo, 1,2,3-triazole and polyhydroxylated aromatics moieties, were designed and synthesized as potential HIV-1 integrase (IN) inhibitors and evaluated their inhibition to the strand transfer process of HIV-1 integrase. The result indicates that 3,4,5-trihydroxylated aromatic derivatives exhibit good inhibition to HIV-1 integrase, but dihydroxylated aromatic derivatives and corresponding methoxy aromatic derivatives appear little inhibition to HIV-1 integrase.
Assuntos
Desenho de Fármacos , Inibidores de Integrase de HIV/síntese química , Inibidores de Integrase de HIV/farmacologia , Integrase de HIV/química , Cetoácidos/química , Ativação Enzimática/efeitos dos fármacos , Integrase de HIV/metabolismo , Inibidores de Integrase de HIV/química , HIV-1/efeitos dos fármacos , Humanos , Cetoácidos/síntese química , Cetoácidos/farmacologia , Relação Estrutura-Atividade , Triazóis/químicaRESUMO
A series of aromatic diketone derivatives were designed and synthesized as potential HIV-1 integrase (IN) inhibitors and evaluated to determine their ability to inhibit the strand transfer process of HIV-1 integrase. The results indicate that (Z)-1-(3-acetyl-2-hydroxy-4,6-dimethoxyphenyl)-3-hydroxy-3-(substituted)phenylprop-2-en-1-one (5a-5d) can moderately inhibit HIV-1 integrase. The cyclization and condensation products (6a-6c and 7e-7f) of compounds 5a-5d show poor inhibitory activity against HIV-1 integrase. The molecular docking results indicate that the different types of compounds act on HIV-1 integrase in different ways, and these results can explain the differences in the inhibitory activities.