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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 9f showed the most potent inhibitory effect against MCF-7 cells, with an IC 50 value of 0.8 μM. Importantly, compound 9f 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.

Antiproliferative Phenothiazine Hybrids as Novel Apoptosis Inducers against MCF-7 Breast Cancer