In vitro antifungal activities of a series of dication-substituted carbazoles, furans, and benzimidazoles.
Aromatic dicationic compounds possess antimicrobial activity against a wide range of eucaryotic pathogens, and in the present study an examination of the structures-functions of a series of compounds against fungi was performed. Sixty-seven dicationic molecules were screened for their inhibitory and fungicidal activities against Candida albicans and Cryptococcus neoformans. The MICs of a large number of compounds were comparable to those of the standard antifungal drugs amphotericin B and fluconazole. Unlike fluconazole, potent inhibitory compounds in this series were found to have excellent fungicidal activities. The MIC of one of the most potent compounds against C. albicans was 0.39 microg/ml, and it was the most potent compound against C. neoformans (MIC, </=0.09 microg/ml). Selected compounds were also found to be active against Aspergillus fumigatus, Fusarium solani, Candida species other than C. albicans, and fluconazole-resistant strains of C. albicans and C. neoformans. Since some of these compounds have been safely given to animals, these classes of molecules have the potential to be developed as antifungal agents.
Del Poeta
M
M
Department of Medicine, Division of Infectious Diseases and International Health, Duke University Medical Center, Durham, North Carolina 27710, USA.
Schell
W A
WA
Dykstra
C C
CC
Jones
S K
SK
Tidwell
R R
RR
Kumar
A
A
Boykin
D W
DW
Perfect
J R
JR
D000935:Antifungal Agents / Q000494:pharmacology*; D001562:Benzimidazoles / Q000494:pharmacology*; D002227:Carbazoles / Q000494:pharmacology*; D004247:DNA / Q000378:metabolism; D005663:Furans / Q000494:pharmacology*; D008826:Microbial Sensitivity Tests; D013329:Structure-Activity Relationship
D000935:Antifungal Agents; D001562:Benzimidazoles; D002227:Carbazoles; D005663:Furans; D004247:DNA