School of Pharmaceutical science, Zhengzhou University, Zhengzhou 450001, China.
Department of Pharmacology, Henan Provincial Institute of Food and Drug Control, Zhengzhou 450008, China.
Molecules. 2018 May 28;23(6):1288. doi: 10.3390/molecules23061288.
We designed a series of novel phenothiazine-1,2,3-triazole hybrids by the molecular hybridization strategy and evaluated their antiproliferative activity against three cancer cell lines (MDA-MB-231, MDA-MB-468 and MCF-7). For the structure-activity relationships, the importance of 1,2,3-triazole and substituents on phenyl ring was explored. Among these phenothiazine-1,2,3-triazole hybrids, compound showed the most potent inhibitory effect against MCF-7 cells, with an IC value of 0.8 μM. Importantly, compound could induce apoptosis against MCF-7 cells by regulating apoptosis-related proteins (Bcl-2, Bax, Bad, Parp, and DR5). These potent phenothiazine-1,2,3-triazole hybrids as novel apoptosis inducers might be used as antitumor agents in the future.
我们设计了一系列新型吩噻嗪-1,2,3-三唑杂合体，通过分子杂交策略进行评估，并研究了它们对三种癌细胞系（MDA-MB-231、MDA-MB-468 和 MCF-7）的抗增殖活性。在结构-活性关系方面，我们探索了 1,2,3-三唑和苯环取代基的重要性。在这些吩噻嗪-1,2,3-三唑杂合体中，化合物 对 MCF-7 细胞表现出最强的抑制作用，IC 值为 0.8 μM。重要的是，化合物 通过调节凋亡相关蛋白（Bcl-2、Bax、Bad、Parp 和 DR5）诱导 MCF-7 细胞凋亡。这些具有潜力的吩噻嗪-1,2,3-三唑杂合体作为新型凋亡诱导剂，将来可能被用作抗肿瘤药物。
