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Semicarbazone derivatives bearing phenyl moiety: synthesis, anticancer activity, cell cycle, apoptosis-inducing and metabolic stability study.
Chemical & Pharmaceutical Bulletin 2019 January 25
A series of semicarbazone derivatives bearing phenyl moiety were synthesized and evaluated for the vitro anticancer activities in four human cancer cell lines (HT29, SK-N-SH, MDA-MB-231 and MKN45). Biological evaluation led to the identification of 11q and 11s, which showed excellent anticancer activities against tested cancer cell lines with IC50 values ranging from 0.32 to 1.57 μM, respectively, while exhibiting weak cytotoxicity on the normal cells (HUVEC). Flow cytometric assay for cell cycle and apoptosis revealed that 11q and 11s caused an arrest in the Sub-G1 cell cycle and inhibited proliferation of cancer cells by inducing apoptosis in a dose-dependent manner. Further enzymatic assay suggested that 11q and 11s could significantly activated procaspase-3 to caspase-3. Metabolic stability study indicated that 11q and 11s showed moderate stability in vitro in human and rat liver microsomes. In view of promising pharmacological activities of 11q and 11s, which had emerged as the valuable lead for further development in the treatment for cancer.
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