TY - JOUR
T1 - Synthesis and Mutagenicity of 5, 11-Dimethylchrysene and Some Methyl-Oxidized Derivatives of 5-Methylchrysene
AU - Amin, Shantilal
AU - Hecht, Stephen S.
AU - LaVoie, Edmond
AU - Hoffmann, Dietrich
PY - 1979/2/1
Y1 - 1979/2/1
N2 - 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.
AB - 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.
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U2 - 10.1021/jm00197a011
DO - 10.1021/jm00197a011
M3 - Article
C2 - 392098
AN - SCOPUS:0018601715
SN - 0022-2623
VL - 22
SP - 1336
EP - 1340
JO - Journal of Medicinal Chemistry
JF - Journal of Medicinal Chemistry
IS - 11
ER -