Design, synthesis and in vitro evaluation of pyridinium ion based cyclase inhibitors and antifungal agents

Article abstract of DOI:10.1016/0968-0896(95)00177-8

The design, synthesis and in vitro biological evaluation of pyridinium ion based inhibitors of oxidosqualene cyclase enzymes are reported. N-Alkyl- and N-prenylpyridinium ions have been found to be potent and specific inhibitors of Candida albicans oxidosqualene-lanosterol cyclase and to exhibit antifungal activity. The ability of pyridinium ions to inhibit the C. albicans cyclase increases with increasing structural resemblance to a putative monocyclized species formed during the course of the cyclization process. The N-(4E,8E)-5,9,13-trimethyl-4,8,12- tetradecatrien-1-ylpyridinium cation 1 inhibits the C. albicans enzyme at concentrations more than 100-fold lower than does the directly analogous piperidinium derivative 4.