Synthesis and mutagenicity of 5,11-dimethylchrysene and some methyl-oxidized derivatives of 5-methylchrysene

J Med Chem. 1979 Nov;22(11):1336-40. doi: 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 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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Chrysenes / chemical synthesis*
  • Chrysenes / toxicity
  • In Vitro Techniques
  • Male
  • Microsomes, Liver / metabolism
  • Mutagens*
  • Oxidation-Reduction
  • Phenanthrenes / chemical synthesis*
  • Rats
  • Rats, Inbred F344
  • Salmonella typhimurium / drug effects
  • Salmonella typhimurium / genetics

Substances

  • Chrysenes
  • Mutagens
  • Phenanthrenes
  • 5,11-dimethylchrysene
  • 5-methylchrysene