title: Anti-UV activity of newly-synthesized water-soluble azulenes.
abstract: BACKGROUND
  We have previously reported that azulene-related compounds can protect cells from UV-induced cytotoxicity. However, due to their high water insolubility, their anti-UV activity could not be accurately determined. In the present study, we newly-synthesized a total of nine derivatives with higher water solubility, and re-investigated their anti-UV activity.
  
  
  METHODS
  Cytotoxicity of these compounds against three human normal oral and three human oral cells squamous cell carcinoma cell lines (OSCCs) was evaluated by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) method. The concentration that reduced the viable cell number by 50% (CC(50)) and the concentration that increased the viability of UV-irradiated cells to 50% (EC(50)) were determined by the dose-response curves. Anti-UV activity (SI) was determined by the ratio of CC(50) to EC(50). The tumor specificity was determined by the ratio of the mean CC(50) value for the normal cells to that for OSCC cells. Apoptosis induction was evaluated by DNA fragmentation and caspase activation.
  
  
  RESULTS
  All compounds except one (sodium 7-isopropyl-3-ethylazulene-1-sulfonate) were new compounds, and showed some tumor specificity (TS value=1.4 to 3.5), without induction of hormesis or apoptosis at lower and higher concentrations, respectively. Sodium 3-methylazulene-1-sulfonate showed the highest tumor specificity and potent anti-UV activity, approximately one half that of sodium ascorbate, the positive control.
  
  
  CONCLUSIONS
  These data suggest the possible applicability of newly-synthesized water-soluble azulenes as skin care products protecting from UV irradiation.
authors.affiliation: Josai University, Sakado, Saitama 350-0295, Japan.
authors.forename: Jun-Ichi
authors.initials: J
authors.lastname: Ueki
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Sakagami
authors.forename: Hidetsugu
authors.initials: H
authors.lastname: Wakabayashi
mesh_terms: D017209:Apoptosis / Q000187:drug effects / Q000528:radiation effects; D052176:Azulenes / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D020169:Caspases / Q000378:metabolism; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D002478:Cells, Cultured; D053938:DNA Fragmentation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation / Q000187:drug effects; D059165:Hormesis / Q000187:drug effects; D006801:Humans; D015394:Molecular Structure; D011837:Radiation-Protective Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D012995:Solubility; D014466:Ultraviolet Rays; D014867:Water / Q000737:chemistry*
chemical_list: D052176:Azulenes; D011837:Radiation-Protective Agents; D014867:Water; D020169:Caspases