Mixture-based heterocyclic combinatorial positional scanning libraries: Discovery of bicyclic guanidines having potent antifungal activities against Candida albicans and Cryptococcus neoformans

A mixture-based synthetic combinatorial Library of more than 100,000 bicycl ic guanidines was generated in a positional scanning format and assayed for activity against Candida albicans. Potent individual bicyclic guanidines w ere directly identified following the screening of the library. Time-kill c urve studies indicated bactericidal activities for the individual bicyclic guanidines. These compounds also showed potent activity against Cryptococcu s neoformans. These studies demonstrate the value of using mixture-based co mbinatorial positional scanning libraries made up of heterocyclic compounds for the rapid identification of novel classes of antifungal compounds.