RESUMO
A solid-state-based mechanochemical process was used to synthesize novel azachalcones and their oximes as tyrosinase inhibitors. Their inhibitory activities on mushroom tyrosinase using l-3,4-dihydroxyphenylalanine as a substrate were investigated. Two of the novel oxime derivatives synthesized were seen to be more potent than the positive control, kojic acid. Both the compounds 1b and 2b inhibited the diphenolase activity of tyrosinase in a dose-dependent manner with their IC50 values of 15.3 and 12.7 µm, respectively. The kinetic analysis showed that their inhibition mechanism was reversible. Both the novel oxime compounds displayed competitive inhibition with their Ki values of 5.1 and 2.5 µm, respectively. This method minimizes waste disposal problems and provides a simple, efficient, and benign method for the synthesis of novel tyrosinase inhibitors for use as skin-whitening agents or as anti-browning food additives.
Assuntos
Agaricales/enzimologia , Compostos Aza/farmacologia , Chalcona/farmacologia , Inibidores Enzimáticos/farmacologia , Monofenol Mono-Oxigenase/antagonistas & inibidores , Oximas/farmacologia , Compostos Aza/síntese química , Compostos Aza/química , Chalcona/análogos & derivados , Chalcona/química , Relação Dose-Resposta a Droga , Inibidores Enzimáticos/síntese química , Inibidores Enzimáticos/química , Cinética , Estrutura Molecular , Monofenol Mono-Oxigenase/metabolismo , Oximas/síntese química , Oximas/química , Relação Estrutura-AtividadeRESUMO
A series of hydroxy-substituted chalcone oxime derivatives were synthesized. These compounds were then evaluated for their inhibitory activities on tyrosinase and melanogenesis in murine B16F10 melanoma cells. The structures of the synthesized compounds were confirmed by (1) H NMR, (13) C NMR, FTIR, and HRMS. Two of the compounds exhibited much higher tyrosinase inhibitory activities (IC50 values of 4.77 and 7.89 µM, respectively) than the positive control, kojic acid (IC50 : 22.25 µM). Kinetic studies revealed them to act as competitive tyrosinase inhibitors with their Ki values of 5.25 and 8.33 µM, respectively. Both the compounds inhibited melanin production and tyrosinase activity in B16 cells. Docking results confirmed that the active inhibitors strongly interacted with the mushroom tyrosinase residues.