Inhibitory effect of some imidazole antifungal compounds on the synthesis of 16-ene-C19-steroid catalyzed by pig testicular microsomes.
The activity of the enzyme (16-ene-C19-steroid synthesizing enzyme) responsible for the conversion of C21-steroids to 16-ene-C19-steroids, which was localized on pig testicular microsomes, was inhibited by some typical imidazole antifungal compounds such as clotrimazole, econazole, miconazole and ketoconazole which are known to be universal inhibitors of cytochrome P-450-dependent enzymes. The 50% inhibitory concentrations of clotrimazole, econazole and miconazole were 0.29, 0.36 and 1.25 microM, respectively for 16-ene-C19-steroid synthesizing enzyme activity. Clotrimazole was the most powerful inhibitor of all the compounds examined, which shows the competitive inhibition for 16-ene-C19-steroid synthesizing enzyme activity. The Ki-value was 0.26 microM for its activity. The degree of the inhibition by these imidazole compounds was very similar to the inhibition of 17 alpha-hydroxylase and C17,20-lyase activities on pig testicular microsomes.
Nakajin
S
S
Department of Biochemistry, Faculty of Pharmaceutical Sciences, Hoshi University, Tokyo, Japan.
Takahashi
K
K
Shinoda
M
M
D000446:Aldehyde-Lyases / Q000378:metabolism; D000728:Androgens / Q000096:biosynthesis*; D000730:Androstadienes / Q000378:metabolism*; D000737:Androstenols / Q000378:metabolism*; D000818:Animals; D000935:Antifungal Agents / Q000494:pharmacology*; D065607:Cytochrome P-450 Enzyme Inhibitors; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D007093:Imidazoles / Q000494:pharmacology*; D008297:Male; D008861:Microsomes / Q000201:enzymology; D011374:Progesterone / Q000378:metabolism; D012724:Sex Attractants / Q000096:biosynthesis*; D013254:Steroid 17-alpha-Hydroxylase / Q000378:metabolism; D013552:Swine; D013737:Testis / Q000378:metabolism*
D000728:Androgens; D000730:Androstadienes; D000737:Androstenols; D000935:Antifungal Agents; D065607:Cytochrome P-450 Enzyme Inhibitors; D007093:Imidazoles; D012724:Sex Attractants; C000152:androsta-5,16-dien-3 beta-ol; C003524:4,16-androstadien-3-one; D011374:Progesterone; D003577:Cytochrome P-450 Enzyme System; D013254:Steroid 17-alpha-Hydroxylase; D000446:Aldehyde-Lyases