Department of Biotechnology and Genetic Engineering, Faculty of Biological Sciences, Islamic University, Kushtia 7003, Bangladesh.
Division of Genome Sciences and Cancer, The John Curtin School of Medical Research and The Shine-Dalgarno Centre for RNA Innovation, The Australian National University, Canberra, ACT 2601, Australia.
Molecules. 2022 Jul 15;27(14):4526. doi: 10.3390/molecules27144526.
L. is widely distributed and commonly used medicinally important herb. It can also be used as a medication for type 2 diabetes patients. In this study, compounds of were screened to investigate the inhibitory action of alpha-amylase and alpha-glucosidase against type 2 diabetes through molecular docking, molecular dynamics simulation, and ADMET (absorption, distribution, metabolism, excretion, and toxicity) analysis. The molecule apigenin-7--glucoside showed the highest binding affinity among 123 (one hundred twenty-three) tested compounds. This compound simultaneously bound with the two-target proteins alpha-amylase and alpha-glucosidase, with high molecular mechanics-generalized born surface area (MM/GBSA) values (ΔG Bind = -45.02 kcal mol for alpha-amylase and -38.288 for alpha-glucosidase) compared with control inhibitor acarbose, which had binding affinities of -36.796 kcal mol for alpha-amylase and -29.622 kcal mol for alpha-glucosidase. The apigenin-7--glucoside was revealed to be the most stable molecule with the highest binding free energy through molecular dynamics simulation, indicating that it could compete with the inhibitors' native ligand. Based on ADMET analysis, this phytochemical exhibited a wide range of physicochemical, pharmacokinetic, and drug-like qualities and had no significant side effects, making them prospective drug candidates for type 2 diabetes. Additional in vitro, in vivo, and clinical investigations are needed to determine the precise efficacy of drugs.
L. 广泛分布且在医学上被广泛应用，是一种重要的药用植物。它也可以作为治疗 2 型糖尿病患者的药物。在这项研究中，筛选了 的化合物，通过分子对接、分子动力学模拟和 ADMET（吸收、分布、代谢、排泄和毒性）分析，研究其对 2 型糖尿病的α-淀粉酶和α-葡萄糖苷酶抑制作用。在所测试的 123 种化合物中，芹菜素-7--葡萄糖苷表现出最高的结合亲和力。该化合物同时与两种靶蛋白α-淀粉酶和α-葡萄糖苷酶结合，与对照抑制剂阿卡波糖相比，具有较高的分子力学-广义 Born 表面面积（MM/GBSA）值（-45.02 kcal/mol 用于α-淀粉酶和-38.288 用于α-葡萄糖苷酶）。阿卡波糖与α-淀粉酶的结合亲和力为-36.796 kcal/mol，与α-葡萄糖苷酶的结合亲和力为-29.622 kcal/mol。分子动力学模拟表明，芹菜素-7--葡萄糖苷是最稳定的分子，具有最高的结合自由能，表明它可以与抑制剂的天然配体竞争。基于 ADMET 分析，这种植物化学物质表现出广泛的物理化学、药代动力学和类药性，并且没有明显的副作用，因此它们可能是 2 型糖尿病的潜在药物候选物。还需要进行更多的体外、体内和临床研究，以确定药物的确切疗效。
