title: Quantitative Structure-cytotoxicity Relationship of 3-Benzylidenechromanones.
abstract: Sixteen 3-benzylidenechromanones were subjected to quantitative structure-activity relationship (QSAR) analysis based on their cytotoxicity and tumor-specificity, in order to examine their new biological activities.
  
  
  
  Cytotoxicity against two human oral squamous cell carcinoma cell lines, two mesenchymal and two epithelial normal oral cells, was determined by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide method. Tumor-specificity (TS) was evaluated by the ratio of the mean CC50(50% cytotoxic concentration) against normal cells to that against tumor cell lines. Physicochemical, structural and quantum-chemical parameters were calculated based on the conformations optimized by the LowModeMD method.
  
  
  
  3-Benzylidenechromanone derivatives that have a methoxy group at 7-position of the chromanone ring and hydroxyl or methoxy group at 4'-position of benzene ring showed relatively higher TS values, exceeding those of doxorubicin (DXR) and 5-fluorouracil (5-FU). Since these anticancer drugs were highly cytotoxic to normal keratinocytes, QSAR analysis was performed with oral carcinoma and mesenchymal normal cells. Tumor-specificity was well correlated with 3D-MoRSE descriptors (that relate to three dimensional shapes) and Edge adjacency indices (that relate to two dimensional shapes and polarization). Introduction of hydroxyl group at 3'-position of benzene ring significantly elevated the tumor-specificity.
  
  
  
  Molecular shape, size and polarization are useful markers for the evaluation of tumor-specificity of 3-benzylidenechromanone derivatives.
authors: Department of Clinical Pharmaceutics, Meiji Pharmaceutical University, Kiyose, Japan uesawa@my-pharm.ac.jp.
authors: Yoshihiro
authors: Y
authors: Uesawa
authors: Division of Pharmacology, Meikai University School of Dentistry, Sakado, Japan.
authors: Hiroshi
authors: H
authors: Sakagami
authors: Department of Clinical Pharmaceutics, Meiji Pharmaceutical University, Kiyose, Japan.
authors: Hajime
authors: H
authors: Kagaya
authors: Faculty of Pharmaceutical Sciences, Josai University, Sakado, Japan.
authors: Marimo
authors: M
authors: Yamashita
authors: Faculty of Pharmaceutical Sciences, Josai University, Sakado, Japan.
authors: Koichi
authors: K
authors: Takao
authors: Faculty of Pharmaceutical Sciences, Josai University, Sakado, Japan.
authors: Yoshiaki
authors: Y
authors: Sugita
mesh_terms: D002294:Carcinoma, Squamous Cell / Q000473:pathology; D045744:Cell Line, Tumor; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D007529:Isoflavones / Q000737:chemistry* / Q000494:pharmacology*; D021281:Quantitative Structure-Activity Relationship
chemical_list: D007529:Isoflavones
keywords: 3-benzylidenechromanones; QSAR analysis; cytotoxicity; mesenchymal and epithelial normal oral cells; oral carcinoma; tumor selectivity