Imidazole antimycotics: selective inhibitors of steroid aromatization and progesterone hydroxylation. 
Econazole, imazalil, and prochloraz, which have broad spectrum antimycotic activity, are shown to be potent inhibitors of steroid aromatase activity of human placental microsomes.  The IC50 values for the inhibition of aromatase activity by econazole, imazalil, miconazole, prochloraz, clotrimazole, ketoconazole, and aminoglutethimide are 0.03, 0.15, 0.6, 0.7, 1.8, 60, and 45 microM, respectively.  Econazole and 4-hydroxyandrostenedione also inhibit the steroid aromatase activity of human fetal liver, a finding which suggests that extraplacental aromatase may have many similarities to the placental enzyme.  Econazole is a more effective inhibitor of placental aromatization of 19-hydroxyandrostenedione than of androstenedione.  This observation is consistent with the competitive nature of the inhibition of aromatase by imidazole antimycotic agents and the reduced affinity of the placental aromatase enzyme for 19-hydroxyandrostenedione compared to androstenedione.  The effectiveness of these imidazole antimycotic agents to inhibit the multiple hydroxylations of progesterone which are catalyzed by human fetal adrenal microsomes is also defined.  While all of the imidazole antimycotic agents are potent inhibitors of the 16 alpha-, 17 alpha-, and 21-hydroxylations of progesterone, selective inhibitory profiles are apparent.  Ketoconazole is a most potent inhibitor of human fetal adrenal progesterone 16 alpha- and 17 alpha-hydroxylases while clotrimazole and imazalil are the most potent inhibitors of progesterone 21-hydroxylase.  These results are strongly supportive that imidazole drugs are selective inhibitors not only of steroid aromatase but also of other microsomal steroid hydroxylases.