title: In-vitro activity of dicationic aromatic compounds and fluconazole against Cryptococcus neoformans and Candida spp.
abstract: We investigated the in-vitro activity of three selected dicationic aromatic compounds for nine clinical isolates of Cryptococcus neoformans and 93 clinical isolates of Candida spp., representing 12 different species, using a broth macrodilution method following NCCLS recommendations. All the clinical isolates were also tested for fluconazole susceptibility. The in-vitro data demonstrate that compounds 39 and 57 have excellent in-vitro activity for all tested strains (MIC 0.19-1.56 mg/L) except Candida pelliculosa. Moreover, compound 39 showed excellent in-vitro fungicidal activity against Candida krusei, Candida glabrata, Candida lusitaniae and Cryptococcus neoformans with MFCs in the range 0.39-6.25 mg/L. Both compounds 39 and 57 showed excellent in-vitro activity against fluconazole-resistant Candida albicans isolates, including a C. albicans strain that contains all known fluconazole-resistant mechanisms. Comparing MIC data from compounds 21, 39 and 57 with fluconazole, we found a statistically significant difference only with compound 39 (P = 0.043). However, comparing MFC data from compounds 21, 39 and 57 with fluconazole, we found statistically significant differences with all three compounds (P < 0.00001). These data indicate the potential antifungal breadth of two bis-benzimidazoles (compounds 39 and 57) as antifungal agents against yeasts. If it can be determined that compounds 39 and 57 are effective and non-toxic in vivo, the prospect of these compounds as clinically useful antifungal agents will be enhanced.
authors.affiliation: Department of Medicine, Duke University Medical Center, Durham, NC 27710, USA.
authors.forename: M
authors.initials: M
authors.lastname: Del Poeta
authors.forename: A S
authors.initials: AS
authors.lastname: Bixel
authors.forename: F
authors.initials: F
authors.lastname: Barchiesi
authors.forename: R R
authors.initials: RR
authors.lastname: Tidwell
authors.forename: D
authors.initials: D
authors.lastname: Boykin
authors.forename: G
authors.initials: G
authors.lastname: Scalise
authors.forename: J R
authors.initials: JR
authors.lastname: Perfect
mesh_terms: D000935:Antifungal Agents / Q000494:pharmacology*; D001562:Benzimidazoles / Q000737:chemistry / Q000494:pharmacology; D002175:Candida / Q000187:drug effects* / Q000302:isolation & purification; D002177:Candidiasis / Q000382:microbiology; D003453:Cryptococcosis / Q000382:microbiology; D003455:Cryptococcus neoformans / Q000187:drug effects* / Q000302:isolation & purification; D004352:Drug Resistance, Microbial; D015725:Fluconazole / Q000494:pharmacology; D005663:Furans / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D008826:Microbial Sensitivity Tests
chemical_list: D000935:Antifungal Agents; D001562:Benzimidazoles; D005663:Furans; D015725:Fluconazole; C039281:furan