Abstract
Despite the rise of new Candida species, Candida albicans tops the list with high morbidity and mortality rates. To tackle this problem there is a need to explore new antifungals that could replace or augment the current treatment options. We previously reported that tosylation of eugenol on hydroxyl group resulted in molecules with enhanced antifungal potency. In line with that work, we synthesized new eugenol tosylate congeners (ETC-1–ETC-7) with different substituents on pendent sulfonyl group and tested their susceptibility against different fluconazole susceptible and resistant C. albicans strains. We evaluated physiology and mode of cell death in response to the most active derivatives by analyzing major apoptotic markers in yeast such as phosphatidylserine externalization, DNA fragmentation, mitochondrial depolarization and decrease in cytochrome c oxidase activity. The results demonstrated that all C. albicans strains were variably susceptible to the test compounds with MIC ranging from 0.125–512 µg/ml, and the most active compounds (ETC-5, ETC-6 and ETC-7) actuate apoptosis and necrosis in Candida cells in a dose-dependent manner via metacaspase-dependent pathway. Furthermore haemolytic assay showed low cytotoxicity effect of these ETCs. Overall the results indicated that ETCs exhibit potential antifungal activity against C. albicans by activating apoptotic and necrotic pathways.
Highlights
Infections with Candida are one of the leading global causes of deaths among sick individuals
We synthesized seven new eugenol tosylate congeners (ETCs) with different substituents on the pendent sulfonyl group and studied their antifungal activity against different C. albicans isolates. We reported that these novel ETCs target 14 α-demethylase (CYP51) enzyme and thereby inhibit ergosterol biosynthesis and significantly downregulates the expression of its related gene ERG11 in C. albicans[15]
Preliminary antifungal susceptibility testing results showed that the test compounds under study (ETC-1–ETC7) have potent antifungal activity against all the tested C. albicans isolates
Summary
Infections with Candida are one of the leading global causes of deaths among sick individuals. With our current clinical settings, there are only few antifungal drugs available to treat the C. albicans infections. Potent antifungal activity of different eugenol tosylate derivatives and their synergistic interaction with fluconazole against different Candida isolates was reported[5]. In the same study it was revealed that these eugenol derivatives inhibit ergosterol biosynthesis in Candida cells. We synthesized seven new eugenol tosylate congeners (ETCs) with different substituents on the pendent sulfonyl group and studied their antifungal activity against different C. albicans isolates. We reported that these novel ETCs target 14 α-demethylase (CYP51) enzyme and thereby inhibit ergosterol biosynthesis and significantly downregulates the expression of its related gene ERG11 in C. albicans[15]. Apoptosis can be triggered by various intrinsic and extrinsic stimuli and induction of apoptosis in yeast cells is considered as powerful model for the screening of new antifungal agents and could provide basis for future therapies
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
