1. Discovery of new chromen-4-one derivatives as telomerase inhibitors through regulating expression of dyskerin.
- Author
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Quan Wang J, Di Yang M, Chen X, Wang Y, Zeng Chen L, Cheng X, and Hua Liu X
- Subjects
- Animals, Antineoplastic Agents chemical synthesis, Antineoplastic Agents chemistry, Apoptosis drug effects, Cell Proliferation drug effects, Dose-Response Relationship, Drug, Enzyme Inhibitors chemical synthesis, Enzyme Inhibitors chemistry, Female, Humans, Liver Neoplasms, Experimental drug therapy, Liver Neoplasms, Experimental pathology, Male, Mice, Mice, Inbred Strains, Models, Molecular, Molecular Structure, Rats, Rats, Sprague-Dawley, Structure-Activity Relationship, Telomerase metabolism, Antineoplastic Agents pharmacology, Cell Cycle Proteins metabolism, Chromans pharmacology, Drug Discovery, Enzyme Inhibitors pharmacology, Nuclear Proteins metabolism, Telomerase antagonists & inhibitors
- Abstract
A series of new trimethoxyphenyl-4H-chromen derivatives as telomerase inhibitors through regulation dyskerin were designed and synthesised. The anticancer activity assay in vitro showed that compound 5i 3-(4-(4-isonicotinoylpiperazin-1-yl)butoxy)-5,7-dimethoxy-2-(3,4,5-trimethoxyphenyl)-4H-chromen-4-one exhibited high activity against Hela, SMMC-7721, SGC-7901, U87 and HepG2 cell lines. Compound 5i also showed potent inhibitory activity against telomerase. The further results confirmed this title compound could significantly improve pathological changes induced rat hepatic tumor in vivo. Preliminary mechanisms showed that compound 5i inhibited telomerase activity through decrease expression of dyskerin.
- Published
- 2018
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