Synthesis, specificity, and antifungal activity of inhibitors of the Candida albicans Δ24-sterol methyltransferase

Mark A. Ator, Stanley J. Schmidt, Jerry L. Adams, Roland E. Dolle, Lawrence I. Kruse, Carrie L. Frey, Janice M. Barone

Research output: Contribution to journalArticlepeer-review

44 Scopus citations


A series of side chain modified analogues of cholesterol and lanosterol (1-10) have been synthesized and evaluated as inhibitors of the Candida albicans Δ24-sterol methyltransferase. Two sterol substrate analogues 1 and 2 which contained a 24-thia substituent were relatively modest inhibitors of the enzyme (K(i) = 1.5-72 μM). Compounds which mimic the carbocation intermediates proposed for the methyltransferase reaction, including sulfonium salts 4-6, amidines 7 and 8, and imidazoles 9 and 10 were substantially more potent inhibitors (K(i) = 5-500 nM). All of the sterol analogues examined displayed less than 10-fold selectivity for inhibition of the methyltransferase versus the rat liver Δ24-sterol reductase. The sterol analogues were tested for in vitro antifungal activity against C. albicans, Candida tropicalis, and Torulopsis glabrata. The minimum inhibitory concentrations versus C. albicans correlated well with the K(i) values for methyltransferase inhibition, and the potency of several compounds approached that of amphotericin B, although only modest fungicidal activity was observed.

Original languageEnglish
Pages (from-to)100-106
Number of pages7
JournalJournal of Medicinal Chemistry
Issue number1
StatePublished - Jan 1 1992


Dive into the research topics of 'Synthesis, specificity, and antifungal activity of inhibitors of the Candida albicans Δ24-sterol methyltransferase'. Together they form a unique fingerprint.

Cite this