RESUMO
Glucokinase (GK) is a new target for the treatment of type II diabetes mellitus (T2DM). In order to find a structure-simplified small molecule GK activator, 19 salicylic acid derivatives were designed and synthesized based on new lead compound (1). Experimental results showed that the potency of compound 8h is superior to control RO-28-0450 in GK activation.
Assuntos
Ativadores de Enzimas/síntese química , Glucoquinase/metabolismo , Hipoglicemiantes/síntese química , Salicilatos/síntese química , Desenho de Fármacos , Ativação Enzimática/efeitos dos fármacos , Ativadores de Enzimas/química , Ativadores de Enzimas/farmacologia , Hipoglicemiantes/química , Hipoglicemiantes/farmacologia , Estrutura Molecular , Salicilatos/química , Salicilatos/farmacologia , Tiazóis/farmacologiaRESUMO
A novel series of sorafenib analogs containing 2-picolinyl hydrazide moiety were designed and synthesized. In vitro, most of synthesized compounds have antiproliferation activity on MDA-MB-231, ACHN, HepG2, Mia-PaCa-2 and SW1990 cell lines tested by MTT assay. It is worth noting that the antitumor activities of compounds 2c, 2d and 2f are more potent than that of sorafenib on pancreatic cancer cells Mia-PaCa-2 and SW1990, and the activities of compounds 3f and 3g are 2-3 times than that of sorafenib on human hepatocellular carcinoma HepG2 cell line.