Studies on mutagenicity of 2 bronchodilators under development in Cuba.
2 pyridoquinazolones, 2-amino-11H-pyrido[2,1-b]quinazolin-11-one (2-APQ) and 11H-pyrido[2,1-b]quinazolin-11-one (PQ), under development as anti-asthma drugs, were studied for mutagenicity. 2-APQ was found to be a strong mutagen in 5 strains of Salmonella typhimurium and a mild one in the forward-mutation system of the yeast Schizosaccharomyces pombe. Furthermore, 2-APQ had strong clastogenic effects in mouse bone marrow. Because of these results, development of 2-APQ as a bronchodilator was stopped. PQ, on the other hand, did not induce mutation in the 5 Salmonella strains or in S. pombe. S9 mix generally increased the response of 2-APQ in Salmonella dramatically. On the contrary, the mutagenic effectiveness of this compound in S. pombe was only slightly higher in the presence of S9 than without it, suggesting that metabolic activation was not effective in this system.
D000818:Animals; D001711:Biotransformation; D001993:Bronchodilator Agents / Q000633:toxicity*; D008297:Male; D008862:Microsomes, Liver / Q000378:metabolism; D009152:Mutagenicity Tests; D009153:Mutagens; D009154:Mutation; D011799:Quinazolines / Q000633:toxicity*; D051381:Rats; D011919:Rats, Inbred Strains; D012486:Salmonella typhimurium / Q000187:drug effects; D012568:Schizosaccharomyces / Q000187:drug effects; D013045:Species Specificity; D013329:Structure-Activity Relationship
D001993:Bronchodilator Agents; D009153:Mutagens; D011799:Quinazolines; C038299:11H-pyrido(2,1-b)quinazolin-11-one; C038298:2-amino-11H-pyrido(2,1-b)quinazolin-11-one