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01-02-2019 | SHORT REPORT

Antitumor evaluation of novel phenothiazine derivatives that inhibit migration and tubulin polymerization against gastric cancer MGC-803 cells

Authors: Nan Liu, Zhe Jin, Jing Zhang, Jianjun Jin

Published in: Investigational New Drugs | Issue 1/2019

Summary

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 1.2 μM. Hybrid 13h could inhibit migration by regulating the expression level of N-cadherin, E-cadherin, Vimentin, and actived-MMP2. Furthermore, it could regulate wnt/β-catenin signaling pathway on MGC-803 cells in a concentration-dependent manner by decreasing the expression level of Wnt5α, β-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.

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Title: Antitumor evaluation of novel phenothiazine derivatives that inhibit migration and tubulin polymerization against gastric cancer MGC-803 cells
Authors: Nan Liu
Zhe Jin
Jing Zhang
Jianjun Jin
Publication date: 01-02-2019
Publisher: Springer US
Published in: Investigational New Drugs / Issue 1/2019
Print ISSN: 0167-6997
Electronic ISSN: 1573-0646
DOI: https://doi.org/10.1007/s10637-018-0682-x

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