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ID: ALA5257099

Journal: Bioorg Med Chem

Title: Design, synthesis and bioactivity evaluations of 8-substituted-quinoline-2-carboxamide derivatives as novel histone deacetylase (HDAC) inhibitors.

Authors: Zhao Y, Yao Z, Ren W, Yang X, Hou X, Cao S, Fang H.

Abstract: The inhibition of histone deacetylases (HDACs) has been considered a promising therapeutic strategy for treatment of many diseases, especially cancer. In the current study, a series of 8-substituted quinoline-2-carboxamide derivatives were designed and synthesized as potent HDAC inhibitors. The most potent compound 21 g (IC50 = 0.050 µM) exhibited 3-fold greater HDAC inhibitory activity compared to the known HDAC inhibitor Vorinostat (IC50 = 0.137 µM). Additionally, compound 21g exhibited low toxicity against normal cells(IC50 in HUVEC cell > 50 µM) and showed good liver microsomal stability, therefore, may serve as a new lead compound for further development.

CiteXplore: 37079967

DOI: 10.1016/j.bmc.2023.117242