Synthesis, Evaluation, and Mechanism Study of New Tepotinib Derivatives as Antiproliferative Agents
Institute of Drug Synthesis and Pharmaceutical Process, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, China
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Academic Editor: Jean Jacques Vanden Eynde
Molecules 2019, 24(6), 1173; https://doi.org/10.3390/molecules24061173
Received: 16 February 2019 / Revised: 18 March 2019 / Accepted: 20 March 2019 / Published: 25 March 2019
(This article belongs to the Collection Efficient Pharmaceutical and Chemical Approaches for Anticancer Therapy: Design, Preliminary Evaluations, and Further Developments)
Inspired by the potent inhibition activity of the c-Met (mesenchymal−epithelial transition factor) inhibitor Tepotinib, a series of new Tepotinib derivatives were synthesized and evaluated for their ability to act as antiproliferative agents to find the leading compounds with good activity and limited side effects. Among them, compound 31e exhibited potent antiproliferative activity (IC50 (50% inhibitory concentration) = 0.026 μΜ) against hepatic carcinoma 97H (human liver cancer cell) cells and, importantly, had very low inhibitory activity against normal cells. A mechanism study demonstrated that 31e induced G1 phase (First growth phase or G indicating gap) arrest, inhibited the phosphorylation of c-Met and its downstream signaling component, Akt (Protein Kinase B), and also inhibited the migration of hepatic carcinoma 97H cells.
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Keywords:
antiproliferative agents; c-Met inhibitor; 97H cells; low toxicity
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MDPI and ACS Style
Zhang, N.-n.; An, B.-j.; Zhou, Y.; Li, X.-s.; Yan, M. Synthesis, Evaluation, and Mechanism Study of New Tepotinib Derivatives as Antiproliferative Agents. Molecules 2019, 24, 1173. https://doi.org/10.3390/molecules24061173
AMA Style
Zhang N-n, An B-j, Zhou Y, Li X-s, Yan M. Synthesis, Evaluation, and Mechanism Study of New Tepotinib Derivatives as Antiproliferative Agents. Molecules. 2019; 24(6):1173. https://doi.org/10.3390/molecules24061173
Chicago/Turabian StyleZhang, Niu-niu; An, Bai-jiao; Zhou, Yan; Li, Xing-shu; Yan, Ming. 2019. "Synthesis, Evaluation, and Mechanism Study of New Tepotinib Derivatives as Antiproliferative Agents" Molecules 24, no. 6: 1173. https://doi.org/10.3390/molecules24061173
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