Cytotoxic and genotoxic effects of some substituted tetrazolo[1,5-c]quinazolines.
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-group, 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 micromol/l) had an acute cytostatic effect manifested by the total inhibition of the cell proliferation. Other concentrations caused a cytotoxicity proportional to the concentration used. The IC50 values were found to be less than 4 microg/ml, a limit put forward by the National Cancer Institute (NCI) for classification of the compound as a potential anticancer drug. BMTQ induced mutations in a dose-related manner, starting from 10 microg/plate in strains TA100 and TA102. Lesser but significant increases in revertant colonies were also obtained in strain TA98. The mutagenity was slightly enhanced by metabolic activation.
Jantová
S
S
Department of Biochemistry and Biology, Faculty of Chemical and Food Technology, Slovak University of Technology, 812 37 Bratislava, Slovak Republic. sona.jantova@stuba.sk
Theiszová
M
M
Mikulásová
M
M
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001419:Bacteria / Q000187:drug effects; D049109:Cell Proliferation; D004354:Drug Screening Assays, Antitumor; D008546:Melanoma, Experimental / Q000188:drug therapy; D051379:Mice; D008826:Microbial Sensitivity Tests; D009152:Mutagenicity Tests; D011799:Quinazolines / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D013777:Tetrazoles / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D011799:Quinazolines; D013777:Tetrazoles