title: Evaluation of cytotoxiciy and tumor-specificity of licorice flavonoids based on chemical structure.
abstract: BACKGROUND
  The mechanism of cytotoxicity induction by flavonoids has been studied by many investigators, but their tumor specificity is not clear. To address this point, 10 licorice flavonoids were subjected to quantitative structure-activity relationship (QASR) analysis with cytotoxicity assay with four human oral carcinoma and three normal cell lines.
  
  
  METHODS
  Cytotoxicity was determined by the 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide method. Physico-chemical, structural, and quantum-chemical parameters were calculated based on the conformations optimized by the LowModeMD method.
  
  
  RESULTS
  Licurazid and isoliquiritigenin had the highest cytotoxicity against tumor cells, and liquiritin, isoliquiritin and licurazid had the highest tumor specificity, suggesting an antitumor potential for licurazid. Chalcones had slightly higher cytotoxicity and tumor specificity than flavanones. The number of sugar units in the molecule was somewhat negatively-correlated with cytotoxicity, but not with tumor specificity. Parameters that reflect the three-dimensional structure, molecular volume and number of phenolic OH groups were significantly correlated with cytotoxicity, but not with tumor specificity. On the other hand, solvation energy was significantly correlated with tumor specificity, but not with cytotoxicity.
  
  
  CONCLUSIONS
  These physicochemical descriptors may be useful to estimate cytotoxicity or tumor specificity of structurally-related compounds to these licorice flavonoids.
authors.affiliation: Maruzen Pharmaceuticals 2-6-7 Ebisunishi, Shibuya, Tokyo, 150-0021, Japan. h-ohno@maruzenpcy.co.jp
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Ohno
authors.forename: Daisuke
authors.initials: D
authors.lastname: Araho
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Uesawa
authors.forename: Hajime
authors.initials: H
authors.lastname: Kagaya
authors.forename: Mariko
authors.initials: M
authors.lastname: Ishihara
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Sakagami
authors.forename: Masaji
authors.initials: M
authors.lastname: Yamamoto
mesh_terms: D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor; D005419:Flavonoids / Q000737:chemistry* / Q000494:pharmacology / Q000627:therapeutic use*; D006035:Glycyrrhiza / Q000737:chemistry*; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy* / Q000473:pathology*; D021281:Quantitative Structure-Activity Relationship
chemical_list: D005419:Flavonoids
keywords: Licorice flavonoids; QSAR; chemical descriptor; cytotoxicity; tumor-specificity index