Abstract：
Inhibition of α-glucosidase and α-amylase are key tactics for managing blood glucose levels. Currently, stronger, and more accessible inhibitors are needed to treat diabetes. Indeno[1,2-b] quinoxalines-carrying thiazole hybrids 1-17 were created and described using NMR. All analogues were tested for hypoglycaemic effect against STZ-induced diabetes in mice. Compounds 4, 6, 8, and 16 were the most potent among the synthesised analogues. These hybrids were examined for their effects on plasma insulin, urea, creatinine, GSH, MDA, ALT, AST, and total cholesterol. Moreover, these compounds were tested against α-glucosidase and α-amylase enzymes in vitro. The four hybrids 4, 6, 8, and 16 represented moderate to potent activity with IC50 values 0.982 ± 0.04, to 10.19 ± 0.21 for α-glucosidase inhibition and 17.58 ± 0.74 to 121.6 ± 5.14 μM for α-amylase inhibition when compared to the standard medication acarbose with IC50=0.316 ± 0.02 μM for α-glucosidase inhibition and 31.56 ± 1.33 μM for α-amylase inhibition. Docking studies as well as in silico ADMT were done.
摘要：
抑制α-葡萄糖苷酶和α-淀粉酶是控制血糖水平的关键策略。目前,更强,和更容易获得的抑制剂需要治疗糖尿病。产生并使用NMR描述携带吲哚[1,2-b]喹喔啉的噻唑杂化物1-17。在小鼠中测试所有类似物对STZ诱导的糖尿病的降血糖作用。在合成的类似物中,化合物4、6、8和16是最有效的。检查了这些杂种对血浆胰岛素的影响，尿素,肌酐,GSH,MDA,ALT,AST,和总胆固醇。此外，这些化合物在体外对α-葡萄糖苷酶和α-淀粉酶进行了测试。四个杂种4、6、8和16表现出中等至有效的活性，IC50值分别为0.982±0.04，α-葡萄糖苷酶抑制为10.19±0.21，α-淀粉酶抑制为17.58±0.74至121.6±5.14μM，与标准药物阿卡波糖相比，α-葡萄糖苷酶抑制为IC50=0.316±0.02μM，α-淀粉酶抑制为31.56±1.33μM。进行了对接研究以及计算机ADMT。
