- Antiproliferative phenothiazine hybrids as novel apoptosis inducers against MCF-7 breast cancer
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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 IC50 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.
- Zhang, Jun-Xia,Guo, Jiao-Mei,Zhang, Ting-Ting,Lin, Hong-Jun,Qi, Nai-Song,Li, Zhen-Guo,Zhou, Ji-Chun,Zhang, Zhen-Zhong
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- Structural requirements for the antitubercular quaternized triflupromazine pharmacophore
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Quaternized triflupromazine derivatives (QTDs) must possess benzyl groups attached to the quaternary nitrogen in order to have significant antitubercular potency. Replacing the quaternary amine with a triazole abolishes antitubercular activity. A modest halogen substitution effect exists, with the 4-bromophenyl QTD 3 having the best selectivity index (>21). All N-benzyl QTDs 1-4 similarly inhibit non-replicating, persistent Mycobacterium tuberculosis with MIC 50 >128 μM).
- Kunciw, Dominique L.,Liechty, Jacob J.,Mitchell, Miguel O.,Wan, Baojie,Franzblau, Scott G.
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