Department of Pharmacognosy, Faculty of Pharmacy, Beni-Suef University, Beni-Suef 62511, Egypt.
Department of Pharmacognosy, Faculty of Pharmacy, Deraya University, 7 Universities Zone, New Minia 61111, Egypt.
Molecules. 2022 Aug 31;27(17):5617. doi: 10.3390/molecules27175617.
Malaria is one of the most important infectious diseases worldwide. The causative of the most severe forms of malaria, , has developed resistances against all the available antimalarial drugs. In the present study, the phytochemical investigation of the green seaweed has afforded two new compounds -, along with 4 known ones -. The structures of the compounds had been confirmed using 1& 2D-NMR and HRESIMS analyses. Extensive machine-learning-supported virtual-screening suggested cytochrome-C enzyme as a potential target for compound . Docking, absolute-binding-free-energy (Δ) and molecular-dynamics-simulation (MDS) of compound revealed the strong binding interaction of this compound with cytochrome-C. In vitro testing for crude extract and isolated compounds revealed the potential in vitro inhibitory activity of both extract and compound against . The crude extract was able to inhibit the parasite growth with an IC value of 1.8 ± 0.35 µg/mL. Compound also showed good inhibitory activity with an IC value of 3.2 ± 0.23 µg/mL. Meanwhile, compound showed moderate inhibitory activity with an IC value of 19.3 ± 0.51 µg/mL. Accordingly, the scaffold of compound can be considered as a good lead compound for the future development of new antimalarial agents.
疟疾是全球最重要的传染病之一。引起最严重疟疾形式的疟原虫已经对所有现有的抗疟药物产生了耐药性。在本研究中，对绿海藻的植物化学研究提供了两种新化合物——和两种已知化合物——。通过 1&2D-NMR 和 HRESIMS 分析确定了化合物的结构。广泛的机器学习支持的虚拟筛选表明细胞色素-C 酶可能是化合物的潜在靶标。化合物的对接、绝对结合自由能（Δ）和分子动力学模拟（MDS）表明，该化合物与细胞色素-C 具有很强的结合相互作用。粗提取物和分离化合物的体外测试显示，提取物和化合物均具有体外抑制疟原虫生长的潜力。粗提取物能以 1.8 ± 0.35 µg/mL 的 IC 值抑制寄生虫生长。化合物也表现出良好的抑制活性，IC 值为 3.2 ± 0.23 µg/mL。同时，化合物表现出中等抑制活性，IC 值为 19.3 ± 0.51 µg/mL。因此，化合物的骨架可以被认为是未来开发新抗疟药物的良好先导化合物。
