Bhowmik Prasenjit, Mallick Rahul, Duttaroy Asim K
Department of Chemistry-BMC, Biochemistry, Disciplinary Domain of Science and Technology, Uppsala University, Uppsala, Sweden.
A.I. Virtanen Institute for Molecular Sciences, Faculty of Health Sciences, University of Eastern Finland, Kuopio, Finland.
Front Chem. 2025 May 27;13:1545834. doi: 10.3389/fchem.2025.1545834. eCollection 2025.
More than a thousand new marine natural products have been isolated each year over the past ten years, and compared to synthetic compounds, the success ratio of approved marine drugs to the total number of reported potential marine natural products is extremely high. In a recent in vitro cytotoxicity test, 11 suberitenones-a class of oxidized sesterterpenes-were identified and shown to have low levels of cytotoxicity. This study focuses on the investigation of the anti-neoplastic ability of of these suberitenones through different in silico analysis.
The study uses a variety of computational techniques, including quantitative structure-activity relationship (QSAR), ADMET, prediction of activity spectra for substances (PASS) prediction, network pharmacology, molecular docking, and molecular dynamics simulation.
The molecular docking showed that Suberitenone I, Secosuberitenone A, and Suberitenone J exhibited higher binding affinity of - 8.9, -9.4, and -8.8 kcal/mole against CASP3, MAPK3, and EGFR respectively which is further supported by molecular dynamics simulation analysis and can be considered for in vitro and in vivo investigation as potential antineoplastic agents.
在过去十年中，每年都有超过一千种新的海洋天然产物被分离出来，与合成化合物相比，已获批的海洋药物在已报道的潜在海洋天然产物总数中的成功率极高。在最近的一项体外细胞毒性试验中，鉴定出了11种苏贝瑞烯酮（一类氧化的倍半萜烯），并显示其细胞毒性水平较低。本研究重点通过不同的计算机模拟分析来研究这些苏贝瑞烯酮的抗肿瘤能力。
该研究使用了多种计算技术，包括定量构效关系（QSAR）、药物代谢及毒性预测（ADMET）、物质活性谱预测（PASS）、网络药理学、分子对接和分子动力学模拟。
分子对接表明，苏贝瑞烯酮I、脱甲苏贝瑞烯酮A和苏贝瑞烯酮J分别对半胱天冬酶3（CASP3）、丝裂原活化蛋白激酶3（MAPK3）和表皮生长因子受体（EGFR）表现出较高的结合亲和力，分别为-8.9、-9.4和-8.8千卡/摩尔，分子动力学模拟分析进一步支持了这一结果，它们可作为潜在的抗肿瘤药物进行体外和体内研究。
