海绵中提取的异臭椿萜类化合物作用靶标的识别

摘要

A strategy combining structure alignment and comparation, target cluster, and invert-docking screening were undertaken to detect the potential bioactivities of several isomalabaricane triterpenoids that were extracted from sponge.The prediction results revealed that the chemicals underwent myocardial ischemia treatment and had antineoplastic bioactivities.Enzymatic bioassays showed that epidermal growth factor receptor (EGFR), focal adhesion kinase (FAK), insulin-like growth factor 1 receptor (IGF1-R), c-Src kinase, and vascular endothelial growth factor receptor 2 (VEGF-R2) were potential targets for these compounds.They had IC50 values ranging from 0.41 g·m-3 (0.41 μg·mL-1) to 9.8 g·m-3 (9.8 μg·mL-1), which is meaningful for the use of these marine natural products as leads for further modifications to new agents.Ligand-target binding mode with these compounds were undertaken and indicated that the four studied chemicals bound well with the targets.%采取了包括化学结构相似性学习、靶标聚类分析以及反向对接筛选等多种方法在内的综合性策略,尝试对中国南海海绵中提取得到的异臭椿萜类化合物进行生物学活性和作用靶标的预测.结果表明:这类化合物具有治疗心肌缺血和抗肿瘤的潜在生物学活性;表皮细胞生长因子受体(EGFR),焦点(局部)粘着斑激酶(FAK),胰岛素样生长因子1受体(IGF1-R),c-Src激酶以及血管表皮生长因子受体2(VEGF-R2)是这类化合物可能的作用靶标.IC50值从0.41 g·m-3(0.41 μg·mL-1)到9.8 g·m-3(9.8 μg·mL-1)不等.活性数据显示这些海绵提取的海洋天然产物可作为先导化合物,通过进一步的优化获得新的药物.同时还讨论了化合物与预测靶标的结合模式,结果显示四个化合物都与相应的受体有较好的结合.