H. E. J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, Pakistan.
H. E. J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, Pakistan; Institute of Marine Biotechnology, Universiti Malaysia Terengannu, 21030 Kuala Terengganu, Terengganu, Malaysia.
Bioorg Med Chem. 2020 Nov 1;28(21):115605. doi: 10.1016/j.bmc.2020.115605. Epub 2020 Aug 15.
One of the most prevailing metabolic disorder diabetes mellitus has become the global health issue that has to be addressed and cured. Different marketed drugs have been made available for the treatment of diabetes but there is still a need of introducing new therapeutic agents that are economical and have lesser or no side effects. The current study deals with the synthesis of indole acrylonitriles (3-23) and the evaluation of these compounds for their potential for α-glucosidase inhibition. The structures of these synthetic molecules were deduced by using different spectroscopic techniques. Acarbose (IC = 2.91 ± 0.02 μM) was used as standard in this study and the synthetic molecules (3-23) have shown promising α-glucosidase inhibitory activity. Compounds 4, 8, 10, 11, 14, 18, and 21 displayed superior inhibition of α-glucosidase enzyme in the range of (IC = 0.53 ± 0.01-1.36 ± 0.04 μM) as compared to the standard acarbose. Compound 10 (IC = 0.53 ± 0.01 μM) was the most effective inhibitor of this library and displayed many folds enhanced activity in contrast to the standard. Molecular docking of synthetic compounds was performed to verify the binding interactions of ligand with the active site of enzyme. This study had identified a number of potential α-glucosidase inhibitors that can be used for further research to identify a potent therapeutic agent against diabetes.
糖尿病是一种流行的代谢紊乱疾病，已成为全球健康问题，必须加以解决和治疗。已经有不同的市售药物可用于治疗糖尿病，但仍需要引入新的治疗剂，这些治疗剂既经济实惠，又副作用较小或没有副作用。本研究涉及吲哚丙烯腈（3-23）的合成及其对α-葡萄糖苷酶抑制潜力的评估。这些合成分子的结构是通过使用不同的光谱技术推导出来的。阿卡波糖（IC = 2.91 ± 0.02 μM）在本研究中用作标准，合成分子（3-23）显示出有希望的α-葡萄糖苷酶抑制活性。与标准阿卡波糖相比，化合物 4、8、10、11、14、18 和 21 对α-葡萄糖苷酶的抑制作用更为优越，抑制范围为（IC = 0.53 ± 0.01-1.36 ± 0.04 μM）。化合物 10（IC = 0.53 ± 0.01 μM）是该库中最有效的抑制剂，与标准相比，其活性增强了多倍。对合成化合物进行了分子对接，以验证配体与酶活性位点的结合相互作用。本研究确定了一些潜在的α-葡萄糖苷酶抑制剂，可用于进一步研究，以确定对抗糖尿病的有效治疗剂。
