Discovery of novel jaspine B analogues as autophagy inducer
Discovery of novel jaspine B analogues as autophagy inducer
复制标题
发现新型茉莉花 B 类似物作为自噬诱导剂
DOI：
10.1016/j.bmcl.2017.12.011
复制
发表时间：
2018
影响因子：
2.7
通讯作者：
Jin Cheng-Yun
中科院分区：
文献类型：
--
作者：
Zhang En;Wang Shang;Li Li-Li;Hua Yong-Gang;Yue Jing-Fei;Li Jin-Feng;Jin Cheng-Yun
合成了一系列2-烷氨基甲基茉莉碱B类似物，并评价了它们对人肺腺癌、乳腺癌、前列腺癌和小鼠黑色素瘤细胞株的细胞毒作用。大多数化合物对癌细胞表现出中等到良好的活性。化合物7f对PC-3细胞的整体细胞毒作用最好(IC_(50)= 0.85 μM)。进一步的机制研究表明，化合物7诱导PC-3细胞形态发生显著变化，扰乱线粒体膜电位，并增加自噬蛋白Beclin-1、Lc3和p62的表达。
A series of 2-alkylaminomethyl jaspine B analogues were synthesized and evaluated for their cytotoxic effects on human lung adenocarcinoma, breast cancer, and prostate cancer cell lines and a mouse melanoma cell line. Most of the compounds exhibited moderate to good activity against the cancer cell lines. Compound7fshowed the best overall cytotoxicity on PC-3 cells (IC50= 0.85 μM). Further mechanistic studies revealed that compound7finduced marked changes in PC-3 cell morphology, disrupted the mitochondrial membrane potential, and increased expression of the autophagy proteins beclin-1, LC3, and P62.