Synthesis and Mutagenicity of 5, 11-Dimethylchrysene and Some Methyl-Oxidized Derivatives of 5-Methylchrysene

Shantilal Amin, Stephen S. Hecht, Edmond LaVoie, Dietrich Hoffmann

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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)-l, 2, 3, 4-tetrahydrochrysene (6), 5-carbomethoxy-l, 2, 3, 4-tetrahydrochrysene (7), and 5H-chryseno[4, 5-fccd]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 hay-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 l, 2-dihydro-l, 2-dihydroxy-5-methylchrysene.

Original languageEnglish (US)
Pages (from-to)1336-1340
Number of pages5
JournalJournal of Medicinal Chemistry
Volume22
Issue number11
DOIs
Publication statusPublished - Feb 1 1979

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All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Drug Discovery

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