Design, synthesis and biological evaluation of chrysin long-chain derivatives as potential anticancer agents.
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 0.048 microM and 0.035 microM), 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.
Lv
Peng-Cheng
PC
State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing 210093, People's Republic of China.
Wang
Kai-Rui
KR
Li
Qing-Shan
QS
Chen
Jin
J
Sun
Juan
J
Zhu
Hai-Liang
HL
D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004354:Drug Screening Assays, Antitumor; D066246:ErbB Receptors / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism*; D005419:Flavonoids / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy; D008958:Models, Molecular; D011485:Protein Binding
D000970:Antineoplastic Agents; D005419:Flavonoids; C043561:chrysin; D066246:ErbB Receptors