Abstract: |
Candida is the most common fungal class, causing both superficial and invasive diseases
in humans. Although Candida albicans is the most common cause of fungal infections in humans, C.
auris is a new emergent serious pathogen causing complications similar to those of C. albicans. Both
C. albicans and C. auris are associated with high mortality rates, mainly because of their multidrug-
resistance patterns against most available antifungal drugs. Although several compounds were
designed against C. albicans, very few or none were tested on C. auris. Therefore, it is urgent to
develop novel effective antifungal drugs that can accommodate not only C. albicans, but also other
Candida spp., particularly newly emergent one, including C. auris. Inspired by the significant broad-
spectrum antifungal activities of the essential oil cuminaldehyde and the reported wide
incorporation of azoles in the antifungal drugs, a series of compounds (UoST1-11) was designed
and developed. The new compounds were designed to overcome the toxicity of the aldehyde group
of cuminaldehyde and benefit from the antifungal selectivity of azoles. The new developed UoST
compounds showed significant anti-Candida activities against both Candida species. The best
candidate compound, UoST5, was further formulated into polymeric nanoparticles (NPs). The new
formula, UoST5-NPs, showed similar activities to the nanoparticles-free drug, while providing only
25% release after 24 h, maintainng prolonged activity up to 48 h and affording no toxicity. In
conclusion, new azole formulations with significantly enhanced activities against C. albicans and C.
auris, while maintaining prolonged action and no toxicities at lower concentrations, were developed.
|
|
|