The effect of methyl substituents on the in vitro metabolism of cyclopenta[a]phenanthren-17-ones: implications for biological activity.
The in vitro metabolism of 15,16-dihydrocyclopenta[a]phenanthren-17-one and its 11- and 12-methyl derivatives has been compared. All three compounds form trans-3,4-dihydrodiols having quasi-diequatorial conformations and 3R,4R configurations. The trans-3,4-dihydrodiol of the mutagenic, but non-tumorigenic 15,16-dihydrocyclopenta[a]phenanthren-17-one appears to undergo stereospecific epoxidation to a syn-diol epoxide. By contrast the 3,4-dihydrodiol of the nontumorigenic 15,16-dihydro-12-methylcyclopenta[a]phenanthren-17-one appears to undergo stereospecific epoxidation to an anti diol-epoxide equivalent to that generated from 15,16-dihydro-11-methylcyclopenta[a]phenanthren-17-one which is a strong carcinogen. These results are discussed with reference to the biological activities of the parent compounds.
D000818:Animals; D001711:Biotransformation; D002273:Carcinogens / Q000378:metabolism*; D006067:Gonanes / Q000378:metabolism*; D006801:Humans; D066298:In Vitro Techniques; D008968:Molecular Conformation; D009705:Nucleosides / Q000378:metabolism; D013329:Structure-Activity Relationship
D002273:Carcinogens; D006067:Gonanes; D009705:Nucleosides; C011770:15,16-dihydrocyclopenta(a)phenanthren-17-one; C043379:15,16-dihydro-12-methylcyclopenta(a)phenanthren-17-one; C005765:15,16-dihydro-11-methylcyclopenta(a)phenanthren-17-one