科研之友
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摘要
Two novel series of 1,2,3-triazole-phenothiazine hybrids and dithiocarbamate-phenothiazine hybrids were designed and synthesized by molecular hybridization strategy. Their antiproliferative activity against three gastric cancer cell lines (MKN28, MGC-803 and MKN45) were evaluated. Among them, hybrid 13h displayed the most potent inhibitory activity against gastric cancer MGC-803 cells with an IC50 value of 1.2M. Hybrid 13h could inhibit migration by regulating the expression level of N-cadherin, E-cadherin, Vimentin, and actived-MMP2. Furthermore, it could regulate wnt/-catenin signaling pathway on MGC-803 cells in a concentration-dependent manner by decreasing the expression level of Wnt5, -catenin and TCF4. From the tubulin polymerization assay results in vitro, hybrid 13h was a novel tubulin polymerization inhibitor. By oral administration assay, compound 13h could effectively inhibit MGC-803 xenograft tumor growth in vivo without obvious side effects. In summary, compound 13h might be an orally active antitumor agent with clinical applications to the treatment of gastric cancer.
