Structure-In Vitro Activity Relationships of Pentamidine Analogues and Dication-Substituted Bis-Benzimidazoles as New Antifungal Agents

Abstract

Twenty analogues of pentamidine, 7 primary metabolites of pentamidine, and 30 dicationic substituted bis-benzimidazoles were screened for their inhibitory and fungicidal activities againstCandida albicans and Cryptococcus neoformans. A majority of the compounds had MICs at which 80% of the strains were inhibited (MIC80s) comparable to those of amphotericin B and fluconazole. Unlike fluconazole, many of these compounds were found to have potent fungicidal activity. The most potent compound against C. albicans had an MIC80 of ≤0.09 μg/ml, and the most potent compound against C. neoformans had an MIC80 of 0.19 μg/ml. Selected compounds were also found to be active againstAspergillus fumigatus, Fusarium solani,Candida species other than C. albicans, and fluconazole-resistant strains of C. albicans and C. neoformans. It is clear from the data presented here that further studies on the structure-activity relationships, mechanisms of action and toxicities, and in vivo efficacies of these compounds are warranted to determine their clinical potential.

Dicationic DNA Minor Groove Binders as Antimicrobial Agents

“…Aromatic diamidines have been reported to have broad-spectrum antimicrobial activity and certain ones have been shown to be effective against Acanthamoeba [10], Aspergillus sp. [11][12][13], Babesia sp. [14,15], Candida albicans [11-13, 16, 17], Cryptococcus neoformans [11][12][13], Cryptosporidium parvum [18,19], Giardia lamblia [20], Leishmania sp.…”

“…[11][12][13], Babesia sp. [14,15], Candida albicans [11-13, 16, 17], Cryptococcus neoformans [11][12][13], Cryptosporidium parvum [18,19], Giardia lamblia [20], Leishmania sp. [21][22][23][24][25], Mycobacterium tuberculosis [16], Plasmodium sp.…”

Solvent-free synthesis of polysubstituted pyrroles catalyzed by ZnO nanorods

“…In addition to this, pyrrole derivatives exhibit remarkable activities such as antitumor [3], anti-HIV [4], anti-inflammatory [5,6], antioxidant [7], antibacterial [8,9], anticandida [10], and antifungal [11]. Therefore, considerable attention has been paid to develop efficient methods for the synthesis of these privileged molecules.…”

Iron-catalyzed selective oxidation of 5-hydroxylmethylfurfural in air: A facile synthesis of 2,5-diformylfuran at room temperature

“…Of particular importance is the transformation of biomass to 1) [2], which can be obtained easily from cellulose [3] and transformed readily to fuels and other value-added chemicals [4]. As one of the most important derivatives of 1, 2,5-diformylfuran (2,5-DFF, 2) has attracted much attention because of its applications in the synthesis of a number of valuable compounds such as pharmaceutical intermediates, fungicides, heterocyclic ligands and others [5][6][7][8]. Early precedents for the oxidation of 1-2, however, suffer from drawbacks such as the use of stoichiometric amount of relatively expensive oxidant (NaOCl, pyridinium chlorochromate etc.)…”