Mixture-based heterocyclic combinatorial positional scanning libraries: discovery of bicyclic guanidines having potent antifungal activities against Candida albicans and Cryptococcus neoformans
Blondelle, S.E.; Crooks, E.; Ostresh, J.M.; Houghten, R.A.
Antimicrobial Agents and ChemoTherapy 43(1): 106-114
1999
ISSN/ISBN: 0066-4804 PMID: 9869574 Document Number: 503992
A mixture-based synthetic combinatorial library of more than 100,000 bicyclic guanidines was generated in a positional scanning format and assayed for activity against Candida albicans. Potent individual bicyclic guanidines were directly identified following the screening of the library. Time-kill curve studies indicated bactericidal activities for the individual bicyclic guanidines. These compounds also showed potent activity against Cryptococcus neoformans. These studies demonstrate the value of using mixture-based combinatorial positional scanning libraries made up of heterocyclic compounds for the rapid identification of novel classes of antifungal compounds.