Synthesis and mutagenicity of 5,11-dimethylchrysene and some methyl-oxidized derivatives of 5-methylchrysene.
A series of compounds structurally related to the carcinogen and mutagen 5-methylchrysene (1) was synthesized and tested for mutagenicity toward S. typhimurium TA 100. The compounds prepared were 5,11-dimethylchrysene (2), 5-(hydroxymethyl)chrysene (3), 5-(acetoxymethyl)chrysene (4), 5-carbomethoxychrysene (5), 5-(hydroxymethyl)-1,2,3,4-tetrahydrochrysene (6), 5-carbomethoxy-1,2,3,4-tetrahydrochrysene (7), and 5H-chryseno[4,5-bcd]pyran-5-one (31). When tested in the presence of rat liver homogenate, 1 and 2 were active while 3--7 were less mutagenic than 1; 31 was highly mutagenic. The mutagenicity of 1 and 2 contrasts with the low activity of 5,12-dimethylchrysene, which supports the generalization that the structural requirements favoring activity are a bay-region methyl group and a free peri position, both adjacent to an unsubstituted angular ring. The low activity of 3--7 indicates that methyl oxidation is not an important activation process for 1. This agrees with previous studies in which the major proximate mutagen and carcinogen of 1 was identified as 1,2-dihydro-1,2-dihydroxy-5-methylchrysene.
D000818:Animals; D002911:Chrysenes / Q000138:chemical synthesis* / Q000633:toxicity; D066298:In Vitro Techniques; D008297:Male; D008862:Microsomes, Liver / Q000378:metabolism; D009153:Mutagens; D010084:Oxidation-Reduction; D010616:Phenanthrenes / Q000138:chemical synthesis*; D051381:Rats; D011916:Rats, Inbred F344; D012486:Salmonella typhimurium / Q000187:drug effects / Q000235:genetics
D002911:Chrysenes; D009153:Mutagens; D010616:Phenanthrenes; C022305:5,11-dimethylchrysene; C008422:5-methylchrysene