title: Quantitative structure-cytotoxicity relationship of 3-styrylchromones.
abstract: BACKGROUND
  Fifteen 3-styrylchromones were subjected to quantitative structure-activity relationship (QSAR) analysis based on their cytotoxicity, tumor selectivity and anti-HIV activity, in order to explore their biological activities.
  
  
  METHODS
  Cytotoxicity against four human oral squamous cell carcinoma (OSCC) cell lines and three human oral normal cells was determined by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) method. Tumor-selectivity 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). Physicochemical, structural and quantum-chemical parameters were calculated based on the conformations optimized by the LowModeMD method followed by the density functional theory (DFT) method.
  
  
  RESULTS
  All 3-styrylchromone derivatives showed moderate-to-high tumor selectivity. Especially, compounds that have a methoxy group at 6-position of the chromone ring and hydroxyl group at 4'-position of phenyl group in styryl moiety [ 11: ] showed the highest tumor-selectivity. On the other hand, their cytotoxicity against normal cells showed good correlation to the descriptors that reflect hydrophobic interaction and molecular shapes.
  
  
  CONCLUSIONS
  Multivariate statistics with chemical descriptors for the location of substituted group, molecular shape and electrostatic interaction may be useful for designing the most favorable compound with higher tumor selectivity.
authors.affiliation: Division of Pharmacology, Meikai University School of Dentistry, Sakado, Saitama, Japan.
authors.forename: Chiyako
authors.initials: C
authors.lastname: Shimada
authors.affiliation: Department of Clinical Pharmaceutics, Meiji Pharmaceutical University, Noshio, Kiyose, Tokyo, Japan.
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Uesawa
authors.affiliation: Department of Clinical Pharmaceutics, Meiji Pharmaceutical University, Noshio, Kiyose, Tokyo, Japan.
authors.forename: Reiko
authors.initials: R
authors.lastname: Ishii-Nozawa
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: 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
authors.affiliation: Division of Pharmacology, Meikai University School of Dentistry, Sakado, Saitama, Japan sakagami@dent.meikai.ac.jp.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Sakagami
mesh_terms: D019380:Anti-HIV Agents / Q000737:chemistry / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology; D002460:Cell Line; D045744:Cell Line, Tumor; 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-styrylchromones; QSAR analysis; anti-HIV activity; cytotoxicity; tumor selectivity