Cytotoxic and genotoxic effects of some substituted tetrazolo[1,5- c]quinazolines
Abstract:
Nine substituted tetrazolo[1,5-c]quinazolines have been tested for cytotoxic effects and structure activity relationship on the murine cancer cell line B16 and four bacterial strains. The most cytotoxic activity had non-substituted in the aromatic ring or substituted by bromo- or chloro- goup, and in the pyrimidine ring of quinazoline skeleton by phenyl or morpholine group, respectively. In the bacterium all tested quinazolines had a lower antibacterial effect than ampicillin. 9-bromo-5-morpholino- tetrazolo[1,5-c]quinazoline (BMTQ) at the highest concentration tested (30.0 µmol/l) had an acute cytostatic effect manifested by the total inhibition of the cell proliferation. Other concentrations caused a cytotoxicity proportional to the concentation used. The IC50 values were found to be less than 4 µg/ml, a limit put forward by the National Cancer Institute (NCI) for clasification of the compound as a potential anticancer drug. BMTQ induced mutations in a dose-related manner, starting from 10 µg/plate in strains TA100 and TA102. Lesser but significant increases in revertant colonies were also obtained in strain TA98. The mutagenity was slighly enhanced by metabolic activation.