title: Quantitative structure-activity relationship analysis of cytotoxicity and anti-UV activity of 2-aminotropones.
abstract: BACKGROUND
  We newly synthesized twenty 2-aminotropones with different lengths of methylene units, with or without introduction of isopropyl group at C-4 position of the cycloheptatriene ring, which were then subjected to quantitative structure-activity relationship (QSAR) analysis.
  
  
  METHODS
  Viable cell number was evaluated by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) method. The tumor specificity was determined by the ratio of the mean CC50 (50% cytotoxic concentration) for the normal cells (human gingival fibroblast, HGF) to that of the human oral squamous cell carcinoma (OSCC) cell line (Ca9-22) derived from gingival tissue. Anti-UV activity (SI) was determined by the ratio of CC50 to EC50 (the concentration that increased the viability of UV-irradiated cells to 50%) using HSC-2 OSCC cells. Physico-chemical, structural, and quantum-chemical parameters were calculated based on conformations optimized by the LowModeMD method followed by the Discrete Fourier Transform (DFT) method. Fine-cell structure was observed by transmission electron microscopy.
  
  
  RESULTS
  2-Aminotropones induced cytotoxicity, accompanied by the production of many rough endoplasmic reticula with enlarged lacuna and vacuolated mitochondria. Their cytotoxicity was a positive function of the number of methylene units and hydrophobicity. Anti-UV activity showed a good correlation with lowest unoccupied molecular orbital (LUMO) energy, but not with the length of methylene units. All twenty 2-aminotropones induced a very low level of hormetic growth stimulation at lower concentrations.
  
  
  CONCLUSIONS
  Different types of chemical descriptors may be applicable to estimating the cytotoxicity and anti-UV activity of 2-aminotropones.
authors.affiliation: Faculty of Science, Josai University, Sakado, Saitama 350-0295, Japan. hwaka@josai.ac.jp/sakagami@dent.meikai.ac.jp.
authors.forename: Shota
authors.initials: S
authors.lastname: Sekine
authors.forename: Chisato
authors.initials: C
authors.lastname: Shimodaira
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Uesawa
authors.forename: Hajime
authors.initials: H
authors.lastname: Kagaya
authors.forename: Yumiko
authors.initials: Y
authors.lastname: Kanda
authors.forename: Mariko
authors.initials: M
authors.lastname: Ishihara
authors.forename: Osamu
authors.initials: O
authors.lastname: Amano
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Sakagami
authors.forename: Hidetsugu
authors.initials: H
authors.lastname: Wakabayashi
mesh_terms: D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002648:Child; D004305:Dose-Response Relationship, Drug; D005260:Female; D005347:Fibroblasts / Q000187:drug effects / Q000528:radiation effects; D006801:Humans; D015394:Molecular Structure; D021281:Quantitative Structure-Activity Relationship; D014334:Tropolone / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology / Q000633:toxicity
chemical_list: C532753:2-aminotropone; D014334:Tropolone
keywords: 2-Aminotropones; QSAR analysis; anti-UV activity; cytotoxicity; fine cell structure