Anti-UV Activity of Newly-synthesized Water-soluble Azulenes

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. Materials and 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-diphenyl-tetrazolium bromide (MTT) method. The concentration that reduced the viable cell number by 50% (CC50) and the concentration that increased the viability of UV-irradiated cells to 50% (EC50) were determined by the dose-response curves. Anti-UV activity (SI) was determined by the ratio of CC50 to EC50. The tumor specificity was determined by the ratio of the mean CC50 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. Conclusion: These data suggest the possible applicability of newly-synthesized water-soluble azulenes as skin care products protecting from UV irradiation.