Synthesis of amidinohydrazones and evaluation of their inhibitory effect towards aldosterone synthase (CYP11B2) and the formation of selected steroids.
The synthesis and biological evaluation of a series of amidinohydrazones (3a-h, 6a-c, 8 and 9) as potential nonsteroidal inhibitors of aldosterone synthase (CYP11B2) are described. The compounds were tested in vitro using CYP11B2-expressing fission yeast; they showed only marginal inhibitory effect. Compound 6c was evaluated for its effect on the formation of aldosterone, cortisol, androstenedione, and DHEA in the adrenocortical tumor cell line NCI-H295R. It exhibited no significant effect on the production of these products.
Voets
Marieke
M
Pharmaceutical and Medicinal Chemistry, Saarland University, Saarbrücken, Germany.
Müller-Vieira
Ursula
U
Marchais-Oberwinkler
Sandrine
S
Hartmann
Rolf W
RW
D000450:Aldosterone / Q000096:biosynthesis; D000578:Amidines / Q000138:chemical synthesis* / Q000494:pharmacology; D000735:Androstenedione / Q000096:biosynthesis; D045744:Cell Line, Tumor; D019405:Cytochrome P-450 CYP11B2 / Q000037:antagonists & inhibitors*; D003687:Dehydroepiandrosterone / Q000096:biosynthesis; D015195:Drug Design; D006801:Humans; D006835:Hydrazones / Q000138:chemical synthesis* / Q000494:pharmacology; D006854:Hydrocortisone / Q000096:biosynthesis; D012568:Schizosaccharomyces / Q000187:drug effects / Q000201:enzymology; D013256:Steroids / Q000096:biosynthesis*
D000578:Amidines; D006835:Hydrazones; D013256:Steroids; D000735:Androstenedione; D003687:Dehydroepiandrosterone; D000450:Aldosterone; D019405:Cytochrome P-450 CYP11B2; D006854:Hydrocortisone