Nguyen Hai Xuan, Le Thu Minh, Le Tho Huu, Truong Thang Quoc, Nguyen Bui Quoc Huy, Nguyen Phong Thanh, Le Khang Minh, Van Do Truong Nhat, Nguyen Mai Thanh Thi, Nguyen Minh Hien, Nguyen Nhan Trung
Faculty of Chemistry, University of Science Ho Chi Minh City Vietnam
Vietnam National University Ho Chi Minh City Vietnam
RSC Adv. 2025 Jul 23;15(32):26444-26454. doi: 10.1039/d5ra01818h. eCollection 2025 Jul 21.
Phytochemical investigation of leaves led to the isolation of three new calaburones (1-3) and 12 known flavones (4-15). Their structures were elucidated by using advanced spectroscopic techniques and compared with existing literature. assay revealed that 12 out of the 15 flavones demonstrated potential α-glucosidase inhibitory activity compared to a positive control, acarbose. The three most potent compounds (3, 14, and 15), having IC values of 5.4, 12.8, and 3.1 μM, respectively, were further investigated using molecular dynamics (MD) simulations to explore the structure-activity relationship (SAR) and assess their interactions with the α-glucosidase enzyme. The SAR analysis suggests that the presence of methoxy groups at C-3 and C-8, along with a hydroxyl group at C-5, plays a crucial role in the α-glucosidase inhibitory activity of these compounds. Molecular docking and molecular dynamics (MD) simulations show that these compounds form strong interactions with key amino acids of α-glucosidase, particularly hydrogen bonds and hydrophobic interactions, leading to the structural stability of the enzyme when bound with the ligand. Compound 15 exhibits the most substantial binding with α-glucosidase, primarily through interactions at the allosteric site, enhancing the stability of the enzyme-ligand complex. These results suggest compound 15 is the most promising candidate for development as an α-glucosidase inhibitor in anti-diabetic drug discovery.
对树叶进行植物化学研究，分离出了三种新的卡拉布酮（1-3）和12种已知的黄酮类化合物（4-15）。通过先进的光谱技术阐明了它们的结构，并与现有文献进行了比较。实验表明，与阳性对照阿卡波糖相比，15种黄酮类化合物中有12种表现出潜在的α-葡萄糖苷酶抑制活性。对三种最有效的化合物（3、14和15）（其IC值分别为5.4、12.8和3.1 μM）进一步进行了分子动力学（MD）模拟研究，以探索构效关系（SAR）并评估它们与α-葡萄糖苷酶的相互作用。SAR分析表明，C-3和C-8位存在甲氧基以及C-5位存在羟基，对这些化合物的α-葡萄糖苷酶抑制活性起着关键作用。分子对接和分子动力学（MD）模拟表明，这些化合物与α-葡萄糖苷酶的关键氨基酸形成强相互作用，特别是氢键和疏水相互作用，与配体结合时导致酶的结构稳定性。化合物15与α-葡萄糖苷酶表现出最强的结合，主要通过变构位点的相互作用，增强了酶-配体复合物的稳定性。这些结果表明，化合物15是抗糖尿病药物研发中最有希望开发成为α-葡萄糖苷酶抑制剂的候选物。
