School of Bio Sciences and Technology, Vellore Institute of Technology, Vellore, Tamil Nadu, India.
Department of Life Science, Kristu Jayanti College, Bengaluru, India.
Curr Cancer Drug Targets. 2019;19(6):495-503. doi: 10.2174/1568009619666181127122230.
The major attention has been received by the natural products in the prevention of diseases due to their pharmacological role.
The major focus of the study was to search for highly potential anti-cancer compounds from marine Streptomyces sp. VITJS4 (NCIM No. 5574).
Cytotoxic assay was examined by MTT assay on HepG2 cells. Bioassay-guided fractionation of the ethyl acetate extract from the fermented broth led to the isolation of the compound. The lead compound structure was elucidated by combined NMR and MS analysis, and the absolute configuration was assigned by extensive spectroscopic analysis.
On the basis of spectroscopic data, the compound was identified as 1, 2 benzenedicarboxylic acid, mono 2-ethylhexyl (BMEH). The compound exhibited in vitro anticancer potential against liver (HepG2) cancer cells. Based on the flow cytometric analysis, it was evident that the BMEH was also effective in arresting the cell cycle at G1 phase. Further, the Western blotting analysis confirmed the down-regulation of Bcl-2 family proteins, and activation of caspase-9 and 3. The molecular docking and dynamics simulation were performed to reveal the activity of the compound over a time period of 10ns. From the molecular dynamics studies, it was found that the stability and compactness were attained by the protein by means of the compound interaction.
This study highlights our collaborative efforts to ascertain lead molecules from marine actinomycete. This is the first and foremost report to prove the mechanistic studies of the purified compound 1, 2-benzene dicarboxylic acid, mono(2-ethylhexyl) ester isolated from marine Streptomyces sp.VITJS4 against HepG2 cells.
由于其药理作用，天然产物在疾病预防方面受到了极大关注。
本研究的主要重点是从海洋链霉菌 sp. VITJS4（NCIM No. 5574）中寻找具有高潜力的抗癌化合物。
通过 MTT 法在 HepG2 细胞上检测细胞毒性。从发酵液的乙酸乙酯提取物中进行生物活性导向分离，得到化合物。通过组合 NMR 和 MS 分析阐明了先导化合物的结构，并通过广泛的光谱分析确定了其绝对构型。
根据光谱数据，该化合物被鉴定为 1,2-苯二甲酸，单 2-乙基己基酯（BMEH）。该化合物表现出体外抗肝癌（HepG2）癌细胞的潜力。基于流式细胞术分析，BMEH 还能有效阻止细胞周期进入 G1 期。此外，Western blot 分析证实了 Bcl-2 家族蛋白的下调，以及 caspase-9 和 3 的激活。进行了分子对接和动力学模拟，以揭示该化合物在 10ns 时间内的活性。从分子动力学研究中发现，通过化合物相互作用，蛋白质获得了稳定性和紧凑性。
本研究强调了我们从海洋放线菌中确定先导分子的合作努力。这是第一个也是最重要的报告，证明了从海洋链霉菌 sp. VITJS4 中分离得到的纯化化合物 1,2-苯二甲酸，单（2-乙基己基）酯对 HepG2 细胞的作用机制研究。
