Design, synthesis and inhibitory activities of naringenin derivatives on human colon cancer cells.

Abstract

Based on the previous result, several naringenin derivatives modified at position 7 with bulky substituents were designed and synthesized, and their inhibitory effects on HCT116 human colon cancer cells were tested using a clonogenic assay. The half maximal inhibitory concentrations (IC(50)) of five naringenin derivatives ranged between 1.20 μM and 20.01 μM which are much better than naringenin used as a control. In addition, new structural modification at C-4 of flavanone results in improving both the anti-cancer effect and anti-oxidative effect. In vitro cyclin dependent kinase 2 (CDK2) binding assay was carried out based on the previous results. To elucidate the possible interaction between naringenin derivatives and CDK2, in silico docking study was performed. This result demonstrates the rationale for the different inhibitory activities of the naringenin derivatives. These findings could be used for designing cancer therapeutic or preventive flavanone-derived agents.

• Authors: Hyuk Yoon, Tae Woo Kim, Soon Young Shin, Mi Joo Park, Yeonjoong Yong, Dong Woon Kim, Tasneem Islam, Young Han Lee, Kang-Yeoun Jung, Yoongho Lim
• Journal: Bioorganic & medicinal chemistry letters (Bioorg Med Chem Lett) Vol. 23 Issue 1 Pg. 232-8 (Jan 01 2013) ISSN: 1464-3405 [Electronic] England
• PMID: 23177257 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2012 Elsevier Ltd. All rights reserved.

Chemical References

• Flavanones
• Cyclin-Dependent Kinase 2
• naringenin
• flavanone

Topics

• Binding Sites
• Cell Survival (drug effects)
• Colonic Neoplasms (metabolism, pathology)
• Cyclin-Dependent Kinase 2 (chemistry, metabolism)
• Drug Design
• Flavanones (chemical synthesis, chemistry, toxicity)
• HCT116 Cells
• Humans
• Molecular Docking Simulation
• Protein Binding
• Protein Structure, Tertiary