title: Quantitative Structure-Cytotoxicity Relationship of 3-Styryl-2H-chromenes.
abstract: BACKGROUND
  Sixteen 3-styryl-2H-chromenes were subjected to quantitative structure-activity relationship analysis based on their cytotoxicity, tumor selectivity and anti-HIV activity, in order to find their new biological activities.
  
  
  METHODS
  Cytotoxicity against four human oral squamous cell carcinoma (OSCC) cell lines, three mesenchymal and two epithelial normal oral cells was determined by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide method. Tumor-selectivity (TS) was evaluated by the ratio of the mean CC50 (50% cytotoxic concentration) against normal human oral cells to that against OSCC cell lines. Anti-HIV activity was evaluated by the ratio of CC50 to EC50 (50% cytoprotective concentration from HIV infection). Potency-selectivity expression (PSE) was determined by the ratio of TS/CC50 against OSCC. Physicochemical, structural and quantum-chemical parameters were calculated based on the conformations optimized by the LowModeMD method.
  
  
  RESULTS
  All 3-styryl-2H-chromene derivatives showed relatively high tumor selectivity. Especially, the compound that has a methoxy group at 7-position of the chromene ring and chlorine at 4'-position of phenyl group in styryl moiety [ 12: ] showed the highest TS and PSE values, exceeding those of resveratrol, doxorubicin and 5-FU. All compounds showed no anti-HIV activity. Among 330 chemical descriptors, 8, 74 and 16 descriptors significantly correlated to the cytotoxicity of normal and tumor cells, and tumor-specificity, respectively.
  
  
  CONCLUSIONS
  Multivariate statistics with chemical descriptors for molecular shape and flatness may be useful for the evaluation of tumor-specificity of 3-styryl-2H-chromenes.
authors.affiliation: Department of Clinical Pharmaceutics, Meiji Pharmaceutical University, Noshio, Kiyose, Tokyo, Japan uesawa@my-pharm.ac.jp.
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Uesawa
authors.affiliation: Division of Pharmacology, Meikai University School of Dentistry, Sakado, Saitama, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Sakagami
authors.affiliation: Division of Basic Chemistry, Meikai University School of Dentistry, Sakado, Saitama, Japan.
authors.forename: Mariko
authors.initials: M
authors.lastname: Ishihara
authors.affiliation: Department of Clinical Pharmaceutics, Meiji Pharmaceutical University, Noshio, Kiyose, Tokyo, Japan.
authors.forename: Hajime
authors.initials: H
authors.lastname: Kagaya
authors.affiliation: St. Marianna University School of Medicine, Kanagawa, Japan.
authors.forename: Taisei
authors.initials: T
authors.lastname: Kanamoto
authors.affiliation: St. Marianna University School of Medicine, Kanagawa, Japan.
authors.forename: Shigemi
authors.initials: S
authors.lastname: Terakubo
authors.affiliation: St. Marianna University School of Medicine, Kanagawa, Japan.
authors.forename: Hideki
authors.initials: H
authors.lastname: Nakashima
authors.affiliation: Faculty of Pharmaceutical Sciences, Josai University, Sakado, Saitama, Japan.
authors.forename: Hideaki
authors.initials: H
authors.lastname: Yahagi
authors.affiliation: Faculty of Pharmaceutical Sciences, Josai University, Sakado, Saitama, Japan.
authors.forename: Koichi
authors.initials: K
authors.lastname: Takao
authors.affiliation: Faculty of Pharmaceutical Sciences, Josai University, Sakado, Saitama, Japan.
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Sugita
mesh_terms: D019380:Anti-HIV Agents / Q000737:chemistry / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology; D002460:Cell Line; D002867:Chromones / Q000737:chemistry* / Q000633:toxicity*; D006801:Humans; D015394:Molecular Structure; D021281:Quantitative Structure-Activity Relationship
chemical_list: D019380:Anti-HIV Agents; D000970:Antineoplastic Agents; D002867:Chromones
keywords: 3-styryl-2H-chromenes; QSAR analysis; anti-HIV activity; cytotoxicity; tumor selectivity