Design, synthesis and biological evaluation of chrysin long-chain derivatives as potential anticancer agents

• Published in: Bioorganic & medicinal chemistry 2010-02, Vol.18 (3), p.1117-1123
• Main Authors: Lv, Peng-Cheng, Wang, Kai-Rui, Li, Qing-Shan, Chen, Jin, Sun, Juan, Zhu, Hai-Liang
• Format: Article
• Language: English
• Subjects: Anticancer; Antineoplastic agents; Antineoplastic Agents - chemical synthesis; Antineoplastic Agents - chemistry; Antineoplastic Agents - pharmacology; Biological and medical sciences; Cell Line, Tumor; Cell Proliferation - drug effects; Chrysin; Drug Screening Assays, Antitumor; EGFR; Flavonoids - chemical synthesis; Flavonoids - chemistry; Flavonoids - pharmacology; General aspects; HT-29; Humans; Liver Neoplasms - drug therapy; Long-chain derivatives; Medical sciences; Models, Molecular; Pharmacology. Drug treatments; Protein Binding; Receptor, Epidermal Growth Factor - antagonists & inhibitors; Receptor, Epidermal Growth Factor - chemistry; Receptor, Epidermal Growth Factor - metabolism
• ISSN: 0968-0896; 1464-3391
• DOI: 10.1016/j.bmc.2009.12.048

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. Compounds 10 and 20 displayed potent EGFR inhibitory activity with IC 50 values of 0.048 μM and 0.035 μM, comparable to the positive control erlotinib. 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 μM and 0.035 μM), 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.