Abubakari Ismail, Kwiyukwa Lucas P, Paul Lucas
Department of Chemistry, The University of Dodoma, P.O.Box 338, Dodoma, Tanzania.
Chemistry Department, College of Natural and Applied Sciences, University of Dar es Salaam, P.O. Box 35061, Dar es Salaam, Tanzania.
BMC Chem. 2025 Jul 3;19(1):196. doi: 10.1186/s13065-025-01527-w.
Malaria remains a critical global health challenge, especially in Sub-Saharan Africa, with drug-resistant strains heightening the need for new treatment strategies. Plasmepsin II, a key enzyme in the life cycle of malaria presents a promising target for novel antimalarial drugs. This study investigates the interaction of luteolin, apigenin and their glycoside derivatives from Allophylus africanus with PMII target using molecular docking, molecular dynamics simulation and free energy calculations. Luteolin derivatives, particularly luteolin-7-O-glucoside and luteolin-3',7-di-O-glucoside showed strong binding with PMII at -9.1 and -9.5 kcal/mol, respectively, while in apigenin derivatives apigenin-6,8-di-C-hexoside exhibited the most significant binding energy (-10.2 kcal/mol). The free energy calculations further confirmed the strong binding affinity with the apigenin-8-C-hexoside, demonstrating the best binding free energy (-86.646 kJ/mol). The study highlights the potential of these compounds as promising candidates for antimalarial drug development, although further experimental validation is needed.
疟疾仍然是一项严峻的全球健康挑战，尤其是在撒哈拉以南非洲地区，耐药菌株增加了对新治疗策略的需求。疟原虫天冬氨酸蛋白酶II（Plasmepsin II）是疟疾生命周期中的一种关键酶，是新型抗疟药物的一个有前景的靶点。本研究使用分子对接、分子动力学模拟和自由能计算，研究了来自非洲异木患（Allophylus africanus）的木犀草素、芹菜素及其糖苷衍生物与PMII靶点的相互作用。木犀草素衍生物，特别是木犀草素-7-O-葡萄糖苷和木犀草素-3',7-二-O-葡萄糖苷，分别以-9.1和-9.5千卡/摩尔的亲和力与PMII紧密结合，而在芹菜素衍生物中，芹菜素-6,8-二-C-己糖苷表现出最显著的结合能（-10.2千卡/摩尔）。自由能计算进一步证实了芹菜素-8-C-己糖苷具有很强的结合亲和力，显示出最佳结合自由能（-86.646千焦/摩尔）。该研究突出了这些化合物作为抗疟药物开发的有前景候选物的潜力，不过还需要进一步的实验验证。
