Optimization and biological evaluation of nicotinamide derivatives as Aurora kinase inhibitors.

ID: ALA4385642

Journal: Bioorg Med Chem

Title: Optimization and biological evaluation of nicotinamide derivatives as Aurora kinase inhibitors.

Authors: Qi B, Xu X, Yang Y, He H, Yue X.

Abstract: Aurora kinases are known to be overexpressed in various solid tumors and implicated in oncogenesis and tumor progression. A series of nicotinamide derivatives were synthesized and their biological activities were evaluated, including kinase inhibitory activity against Aur A and Aur B and in vitro antitumor activity against SW620, HT-29, NCI-H1975 and Hela cancer cell lines. In addition, the study of antiproliferation, cytotoxicity and apoptosis was performed meanwhile. As the most potent inhibitor of Aur A, 4-((3-bromo-4-fluorophenyl)amino)-6-chloro-N-(4-((6,7-dimethoxyquinolin-4-yl)oxy)-3-fluorophenyl)nicotinamide (10l) showed excellent antitumor activity against SW620 and NCI-H1975 with IC₅₀ values were 0.61 and 1.06 μM, while the IC₅₀ values of reference compound were 3.37 and 6.67 μM, respectively. Furthermore, binding mode studies indicated that compound 10l forms better interaction with Aur A.

CiteXplore: 31307762

DOI: 10.1016/j.bmc.2019.07.016

Patent ID: ┄