Department of Clinical Pharmacy Research, Institute for Research and Medical Consultations (IRMC), Imam Abdulrahman Bin Faisal University, P.O. Box 31441, Dammam, Saudi Arabia.
Atta-ur-Rahman Institute for Natural Product Discovery, Universiti Teknologi MARA (UiTM), Puncak Alam Campus, 42300 Bandar Puncak Alam, Selangor, Malaysia.
Bioorg Chem. 2021 May;110:104808. doi: 10.1016/j.bioorg.2021.104808. Epub 2021 Mar 10.
We have synthesized new hybrid class of indole bearing sulfonamide scaffolds (1-17) as α-glucosidase inhibitors. All scaffolds were found to be active except scaffold 17 and exhibited IC values ranging from 1.60 to 51.20 µM in comparison with standard acarbose (IC = 42.45 µM). Among the synthesized hybrid class scaffolds 16 was the most potent analogue with IC value 1.60 μM, showing many folds better potency as compared to standard acarbose. Whereas, synthesized scaffolds 1-15 showed good α-glucosidase inhibitory potential. Based on α-glucosidase inhibitory effect, Scaffold 16 was chosen due to highest activity in vitro for further evaluation of antidiabetic activity in Streptozotocin induced diabetic rats. The Scaffold 16 exhibited significant antidiabetic activity. All analogues were characterized through H, CNMR and HR MS. Structure-activity relationship of synthesized analogues was established and confirmed through molecular docking study.
我们合成了一类新型的吲哚磺酰胺杂合支架(1-17)作为α-葡萄糖苷酶抑制剂。所有支架都具有活性,除了支架 17,其 IC 值在 1.60 到 51.20 μM 之间,与标准阿卡波糖(IC = 42.45 μM)相比。在所合成的杂合支架中,16 是最有效的类似物,IC 值为 1.60 μM,与标准阿卡波糖相比具有多倍的效力。而,合成的支架 1-15 表现出良好的α-葡萄糖苷酶抑制潜力。基于α-葡萄糖苷酶抑制作用,选择了支架 16,因为它在体外具有最高的活性,用于进一步评估链脲佐菌素诱导的糖尿病大鼠的抗糖尿病活性。支架 16 表现出显著的抗糖尿病活性。所有的类似物都通过 H、CNMR 和 HR MS 进行了表征。通过分子对接研究建立并确认了合成类似物的构效关系。