Abstract
Candida albicans, along with some other non-albicans Candida species, is a group of yeast, which causes serious infections in humans that can be both systemic and superficial. Despite the fact that extensive efforts have been put into the discovery of novel antifungal agents, the frequency of these fungal infections has increased drastically worldwide. In our quest for the discovery of novel antifungal compounds, we had previously synthesized and screened quinoline containing 1,2,3-triazole (3a) as a potent Candida spp inhibitor. In the present study, two structural analogues of 3a (3b and 3c) have been synthesized to determine the role of quinoline and their anti-Candida activities have been evaluated. Preliminary results helped us to determine 3a and 3b as lead inhibitors. The IC50 values of compound 3a for C. albicans ATCC 90028 (standard) and C. albicans (fluconazole resistant) strains were 0.044 and 2.3 μg/ml, respectively while compound 3b gave 25.4 and 32.8 μg/ml values for the same strains. Disk diffusion, growth and time kill curve assays showed significant inhibition of C. albicans in the presence of compounds 3a and 3b. Moreover, 3a showed fungicidal nature while 3b was fungistatic. Both the test compounds significantly lower the secretion of proteinases and phospholipases. While, 3a inhibited proteinase secretion in C. albicans (resistant strain) by 45%, 3b reduced phospholipase secretion by 68% in C. albicans ATCC90028 at their respective MIC values. Proton extrusion and intracellular pH measurement studies suggested that both compounds potentially inhibit the activity of H+ ATPase, a membrane protein that is crucial for various cell functions. Similarly, 95–97% reduction in ergosterol content was measured in the presence of the test compounds at MIC and MIC/2. The study led to identification of two quinoline based potent inhibitors of C. albicans for further structural optimization and pharmacological investigation.
Highlights
Sincere efforts are being continuously made for discovering new antifungal targets and drugs, the frequency of human fungal infections has increased drastically worldwide, [1,2,3]
We reported the synthesis and anti-Candida activities of eight novel 1,2,3 triazole derivatives (3a-h) and found that compound 3a displayed better activity than its natural bioactive compound 8-hydroxy quinoline. This compound showed an Concentration required for 50% inhibition (IC50) of 0.044, 12.02 and 3.60 μg/mL against C. albicans, C. glabrata and C. tropicalis, respectively. This enhanced anticandidal activity of compound 3a may be due to the presence of quinoline ring along with 1,2,3 triazole ring in its structure [20]
The results indicate that N-atom plays an important role in the anticandidal activity and quinoline is a key moiety along with 1,2,3 triazole ring in the structure of these synthesized compounds
Summary
Sincere efforts are being continuously made for discovering new antifungal targets and drugs, the frequency of human fungal infections has increased drastically worldwide, [1,2,3]. Particular concern are the ever-increasing incidences of hospital-acquired systemic mycoses caused by Candida species responsible for crude mortality rates of up to 50% in the United States alone [4]. Adding to this disease burden, superficial infections of skin and nails in humans are affecting ~25% of the general population worldwide [5]. Among different Candida spp, C. albicans is the major cause of candidiasis and accounts for 80% of the isolates from all forms of human candidiasis [7]. The number of infections caused by other non-albicans Candida species which includes C. glabrata, C. tropicalis, and C. parapsilosis has increased significantly [8]
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
