Design Synthesis and Structural Characterization of Novel Diazaphenothiazines with 123-Triazole Substituents as Promising Antiproliferative Agents

摘要

A series of novel 1,2,3-triazole-diazphenothiazine hybrids was designed, synthesized, and evaluated for anticancer activity against four selected human tumor cell lines (SNB-19, Caco-2, A549, and MDA-MB231). The majority of the synthesized compounds exhibited significant potent activity against the investigated cell lines. Among them, compounds and showed excellent broad spectrum anticancer activity, with IC values ranging from 0.25 to 4.66 μM and 0.25 to 6.25 μM, respectively. The most promising compound , possessing low cytotoxicity against normal human fibroblasts NHFF, was used for gene expression analysis using reverse transcription–quantitative real-time PCR (RT–qPCR). The expression of and genes revealed that these compounds inhibited the proliferation in all cells ( ) and activated mitochondrial events of apoptosis ( ).