Design, synthesis and biological evaluation of chrysin long-chain derivatives as potential anticancer agents.
Bioorganic & medicinal chemistry 2009 Dec 24; In press
Lv P PC, Wang K KR, Li Q QS, Chen J, Sun J, Zhu H HL
State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing 210093, People's Republic of China.
A series of long-chain derivatives of chrysin (compounds 3-22) were synthesized to evaluate for their antiproliferative activities against the human liver cancer cell line HT-29 and EGFR inhibitory activity. Among the compounds tested, compounds hexadecyl 2-(5-hydroxy-4-oxo-2-phenyl-4H-chromen-7-yloxy)acetate (10) and N-hexadecyl 2-(5-hydroxy-4-oxo-2-phenyl-4H-chromen-7-yloxy)acetamide (20) displayed potent EGFR inhibitory activity with IC(50) values of 0.048muM and 0.035muM), comparable to the positive control erlotinib. Docking simulation of compounds 10 and 20 was carried out to illustrate the binding mode of the molecular into the EGFR active site, and the result suggested that compound 10 and 20 can bind the EGFR kinase well. Thus, compounds 10 and 20 with potent EGFR inhibitory activity would be potential anticancer agents.
Keywords: EGFR