title: 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.affiliation: Division of Bioscience and Biotechnology, BMIC, Konkuk University, Seoul 143-701, Republic of Korea.
authors.forename: Hyuk
authors.initials: H
authors.lastname: Yoon
authors.forename: Tae Woo
authors.initials: TW
authors.lastname: Kim
authors.forename: Soon Young
authors.initials: SY
authors.lastname: Shin
authors.forename: Mi Joo
authors.initials: MJ
authors.lastname: Park
authors.forename: Yeonjoong
authors.initials: Y
authors.lastname: Yong
authors.forename: Dong Woon
authors.initials: DW
authors.lastname: Kim
authors.forename: Tasneem
authors.initials: T
authors.lastname: Islam
authors.forename: Young Han
authors.initials: YH
authors.lastname: Lee
authors.forename: Kang-Yeoun
authors.initials: KY
authors.lastname: Jung
authors.forename: Yoongho
authors.initials: Y
authors.lastname: Lim
mesh_terms: D001665:Binding Sites; D002470:Cell Survival / Q000187:drug effects; D003110:Colonic Neoplasms / Q000378:metabolism / Q000473:pathology; D051357:Cyclin-Dependent Kinase 2 / Q000737:chemistry / Q000378:metabolism; D015195:Drug Design; D044950:Flavanones / Q000138:chemical synthesis / Q000737:chemistry* / Q000633:toxicity; D045325:HCT116 Cells; D006801:Humans; D062105:Molecular Docking Simulation; D011485:Protein Binding; D017434:Protein Structure, Tertiary
chemical_list: D044950:Flavanones; D051357:Cyclin-Dependent Kinase 2; C005273:naringenin; C028610:flavanone