A study of chemical carcinogenesis. 19. Synthesis and mutagenicity of 5,11-dimethylchrysene and some methyl-oxidized derivatives of 5-methylchrysene
- 1 November 1979
- journal article
- research article
- Published by American Chemical Society (ACS) in Journal of Medicinal Chemistry
- Vol. 22 (11), 1336-1340
- https://doi.org/10.1021/jm00197a011
Abstract
A series of compounds structurally related to the carcinogen and mutagen 5-methylchrysene (1) was synthesized and tested for mutagenicity toward Salmonella 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 (8). When tested in the presence of rat liver homogenate, 1 and 2 were active while 3, 4, 5, 6 and 7 were less mutagenic than 1; 8 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, 4, 5, 6 and 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.This publication has 8 references indexed in Scilit:
- Identification of four trans-3,4-dihydrodiol metabolites of 7,12-dimethylbenz[a]anthracene and their in vitro DNA-binding activities upon further metabolism.Proceedings of the National Academy of Sciences, 1978
- STUDY OF CHEMICAL CARCINOGENESIS .9. 1,2-DIHYDRO-1,2-DIHYDROXY-5-METHYLCHRYSENE, A MAJOR ACTIVATED METABOLITE OF ENVIRONMENTAL CARCINOGEN 5-METHYLCHRYSENE1978
- METABOLIC ACTIVATION OF 3-METHYLCHOLANTHRENE AND ITS METABOLITES TO PRODUCTS MUTAGENIC TO BACTERIAL AND MAMMALIAN-CELLS1978
- EVIDENCE FOR BAY REGION ACTIVATION OF CHRYSENE 1,2-DIHYDRODIOL TO AN ULTIMATE CARCINOGEN1978
- STUDY CHEMICAL CARCINOGENESIS .8. TUMOR-INITIATING ACTIVITY OF FLUORINATED 5-METHYLCHRYSENES1978
- Study of chemical carcinogenesis. 7. Synthesis and mutagenicity of modified chrysenes related to the carcinogen, 5-methylchryseneJournal of Medicinal Chemistry, 1978
- High mutagenicity of metabolically activated chrysene 1,2 dihydrodiol: Evidence for bay region activation of chryseneBiochemical and Biophysical Research Communications, 1977
- EVALUATION OF MUTAGENICITY OF COMPOUNDS OF KNOWN CARCINOGENICITY, BELONGING TO BENZ[A]ANTHRACENE, CHRYSENE, AND CYCLOPENTA[A]PHENANTHRENE SERIES, USING AMESS TEST1976