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Antimicrobial Agents and Chemotherapy, October 1998, p. 2503-2510, Vol. 42, No. 10
0066-4804/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.

In Vitro Antifungal Activities of a Series of Dication-Substituted Carbazoles, Furans, and Benzimidazoles

Maurizio Del Poeta,1,2 Wiley A. Schell,1 Christine C. Dykstra,3 Susan K. Jones,4 Richard R. Tidwell,4 Arvind Kumar,5 David W. Boykin,5 and John R. Perfect1,*

Department of Medicine, Division of Infectious Diseases and International Health, Duke University Medical Center, Durham, North Carolina 277101; Department of Pathobiology, Auburn University, Auburn, Alabama 368493; Department of Pathology and Laboratory Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 275994; Department of Chemistry, Georgia State University, Atlanta, Georgia 303035; and Institute of Infectious Diseases and Public Health, University of Ancona, Ospedale Umberto I°, 60121 Ancona, Italy2

Received 23 March 1998/Returned for modification 22 April 1998/Accepted 10 July 1998

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 µg/ml, and it was the most potent compound against C. neoformans (MIC, <= 0.09 µg/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.

* Corresponding author. Mailing address: Department of Medicine, Division of Infectious Diseases and International Health, Duke University Medical Center, P.O. Box 3353, Durham, NC 27710. Phone: (919) 684-2660. Fax: (919) 684-8902. E-mail: perfe001{at}mc.duke.edu.

Antimicrobial Agents and Chemotherapy, October 1998, p. 2503-2510, Vol. 42, No. 10
0066-4804/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.


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