title: Benzoflavonoids Structure Hinders Human Colon Cancer Clonogenicity.
abstract: BACKGROUND
  Since flavonoids fused by benzene have been known for their potent chemopreventive effects, in this study, we examined the relationship between the structures and activities of benzoflavones, benzoflavanones, benzochalcones, and benzochalcone derivatives bearing the pyrazole moiety against human colon cancer cells.
  
  
  METHODS
  We investigated the effect of 34 benzoflavonoids on the inhibition of colon cancer cells based on the clonogenicity. The biological activity values used for the quantitative structure-activity relationship (QSAR) calculations were obtained from the cell growth inhibition on the basis of clonogenicity. 3D-QSAR calculations were performed using comparative molecular field analyses (CoMFA) and comparative molecular similarity index analyses (CoMSIA).
  
  
  RESULTS
  Of several CoMFA and CoMSIA models, the best models showing the highest cross validated correlation coefficient were selected and validated. The cell growth inhibition values were calculated using the above models. The structural conditions to show good cell growth inhibitory effects on human colon cancer cells were analyzed by CoMFA and CoMSIA contour maps. The contribution of steric fields remarkably decreased without any change in the contribution of the electrostatic field, which means that electrostatic contribution is more crucial than the steric contribution in the modification of benzoflavonoids. Furthermore, the increase in the hydrogen bond donor contribution was approximately proportional to the decrease in steric field contribution.
  
  
  CONCLUSIONS
  This study demonstrated that benzoflavonoids structure hinders colon cancer clonogenicity. Most of the benzoflavonoids structures comprised a C-3 linkage between the naphthalene and phenyl moieties, which contained diverse functional moieties such as oxygen-fused rings, double bonds, pyrazole rings, and sulfur constituents, and were able to exhibit great potential in diverse anticancer effects. Also, the positions of the hydroxyl group close to the naphthalene and phenyl rings were crucial for activity against colon cancer. The structural conditions obtained here may help us design potent benzoflavonoids against colon cancer cells and predict their activities.
authors.forename: Yeonjoong
authors.initials: Y
authors.lastname: Yong
authors.forename: Eun J
authors.initials: EJ
authors.lastname: Koh
authors.forename: Seunghyun
authors.initials: S
authors.lastname: Ahn
authors.forename: Beom S
authors.initials: BS
authors.lastname: Kim
authors.forename: Young H
authors.initials: YH
authors.lastname: Lee
authors.affiliation: Department of Biological Science, Konkuk University, Seoul, 143-701, Korea.
authors.forename: Soon Y
authors.initials: SY
authors.lastname: Shin
authors.affiliation: Division of Bioscience and Biotechnology, BMIC, Konkuk University, Seoul 143-701, Korea.
authors.forename: Yoongho
authors.initials: Y
authors.lastname: Lim
mesh_terms: D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000473:pathology*; D005419:Flavonoids / Q000737:chemistry* / Q000494:pharmacology*; D006801:Humans; D008958:Models, Molecular; D008968:Molecular Conformation; D011720:Pyrazoles / Q000737:chemistry; D021281:Quantitative Structure-Activity Relationship
chemical_list: D005419:Flavonoids; D011720:Pyrazoles
keywords: Benzoflavonoid; CoMFA; CoMSIA; benzochalcone; clonogenicity; colon cancer