AI Article Synopsis
- Aurora kinases are often overexpressed in solid tumors and play a role in cancer development and growth.
- Researchers synthesized nicotinamide derivatives to test their effectiveness as inhibitors of Aur A and Aur B, along with their antitumor effects on various cancer cell lines.
- The most effective compound, 10l, demonstrated strong antitumor activity with lower inhibitory concentration values compared to a reference compound and showed better binding interactions with Aur A.
Article 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 IC values were 0.61 and 1.06 μM, while the IC 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.
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| http://dx.doi.org/10.1016/j.bmc.2019.07.016 | DOI Listing |
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