Department of Pharmaceutical Chemistry, University of Dhaka, Dhaka 1000, Bangladesh.
Department of Pharmacy, University of Asia Pacific, 74/A, Green Road, Dhaka 1205, Bangladesh.
Molecules. 2022 Nov 24;27(23):8191. doi: 10.3390/molecules27238191.
A new dimeric prenylated quinolone alkaloid, named 2,11-didemethoxy-vepridimerine A, was isolated from the root bark of , together with twelve known compounds. The structure of the new compound was elucidated on the basis of spectroscopic investigations (NMR and Mass). The interaction of the isolated compounds with the main protease of SARS-CoV-2 (Mpro) was evaluated using molecular docking followed by MD simulations. The result suggests that 2,11-didemethoxy-vepridimerine A, the new compound, has the highest negative binding affinity against the Mpro with a free energy of binding of -8.5 Kcal/mol, indicating interaction with the Mpro. This interaction was further validated by 100 ns MD simulation. This implies that the isolated new compound, which can be employed as a lead compound for an Mpro-targeting drug discovery program, may be able to block the action of Mpro.
从 根皮中分离得到了一种新的二聚倍半萜喹诺酮生物碱，命名为 2,11-二甲氧基-vepridimerine A，同时还分离得到了 12 种已知化合物。新化合物的结构是基于光谱研究（NMR 和 Mass）阐明的。采用分子对接结合 MD 模拟的方法评估了分离得到的化合物与 SARS-CoV-2 主要蛋白酶（Mpro）的相互作用。结果表明，新化合物 2,11-二甲氧基-vepridimerine A 对 Mpro 具有最高的负结合亲和力，结合自由能为-8.5 Kcal/mol，表明与 Mpro 相互作用。这种相互作用通过 100 ns MD 模拟得到了进一步验证。这意味着，作为一种针对 Mpro 的药物发现计划的先导化合物，所分离的新型化合物可能能够阻断 Mpro 的作用。
