Department of Computer Information Systems, College of Computer Science & Information Technology (CCSIT), Imam Abdulrahman Bin Faisal University, P.O. Box 1982, Dammam 31441, Saudi Arabia.
Department of Clinical Pharmacy, Institute for Research and Medical Consultations (IRMC), Imam Abdulrahman Bin Faisal University, P.O. Box 1982, Dammam 31441, Saudi Arabia.
Bioorg Chem. 2018 Oct;80:112-120. doi: 10.1016/j.bioorg.2018.06.001. Epub 2018 Jun 2.
In search of better α-glucosidase inhibitors, a series of bis-indolylmethane sulfonohydrazides derivatives (1-14) were synthesized and evaluated for their α-glucosidase inhibitory potential. All derivatives exhibited outstanding α-glucosidase inhibition with IC values ranging between 0.10 ± 0.05 to 5.1 ± 0.05 μM when compared with standard drug acarbose having IC value 856.28 ± 3.15 μM. Among the series, analog 7 (0.10 ± 0.05 μM) with tri-chloro substitution on phenyl ring was identified as the most potent inhibitor of α-glucosidase (∼ 8500 times). The structure activity relationship has been also established. Molecular docking studies were also performed to help understand the binding interaction of the most active analogs with receptors. From the docking studies, it was observed that all the active bis-indolylmethane sulfonohydrazides derivatives showed considerable binding interactions within the active site (acarbose inhibition site) of α-glucosidase. We also evaluated toxicity of all derivatives and found none of them are toxic.
为了寻找更好的α-葡萄糖苷酶抑制剂，我们合成了一系列双吲哚基甲烷磺酰腙衍生物（1-14），并评估了它们对α-葡萄糖苷酶的抑制潜力。与标准药物阿卡波糖（IC 值为 856.28±3.15μM）相比，所有衍生物均表现出出色的α-葡萄糖苷酶抑制活性，IC 值在 0.10±0.05 至 5.1±0.05μM 之间。在该系列中，苯环上带有三氯取代基的类似物 7（0.10±0.05μM）被鉴定为α-葡萄糖苷酶（约 8500 倍）最有效的抑制剂。还建立了构效关系。还进行了分子对接研究，以帮助了解最活跃的类似物与受体的结合相互作用。从对接研究中可以看出，所有活性双吲哚基甲烷磺酰腙衍生物都在α-葡萄糖苷酶的活性部位（阿卡波糖抑制部位）表现出相当大的结合相互作用。我们还评估了所有衍生物的毒性，发现它们都没有毒性。
