Inhibitors of the glyoxylate cycle enzyme ICL1 in Candida albicans for potential use as antifungal agents.
Candida albicans is an opportunistic pathogen that causes candidiasis in humans. In recent years, metabolic pathways in C. albicans have been explored as potential antifungal targets to treat candidiasis. The glyoxylate cycle, which enables C. albicans to survive in nutrient-limited host niches and its. Key enzymes (e.g., isocitrate lyase (ICL1), are particularly attractive antifungal targets for C. albicans. In this study, we used a new screening approach that better reflects the physiological environment that C. albicans cells experience during infection to identify potential inhibitors of ICL. Three compounds (caffeic acid (CAFF), rosmarinic acid (ROS), and apigenin (API)) were found to have antifungal activity against C. albicans when tested under glucose-depleted conditions. We further confirmed the inhibitory potential of these compounds against ICL using the ICL enzyme assay. Lastly, we assessed the bioavailability and toxicity of these compounds using Lipinski's rule-of-five and ADMET analysis.
Infectomic Cluster, Advanced Medical & Dental Institute, Universiti Sains Malaysia, Penang, Malaysia.
Hong-Leong
HL
Cheah
Integrative Medicine Cluster, Advanced Medical and Dental Institute, Universiti Sains Malaysia, Penang, Malaysia.
Vuanghao
V
Lim
Infectomic Cluster, Advanced Medical & Dental Institute, Universiti Sains Malaysia, Penang, Malaysia.
Doblin
D
Sandai
D000935:Antifungal Agents / Q000494:pharmacology*; D047310:Apigenin / Q000494:pharmacology; D002109:Caffeic Acids / Q000494:pharmacology; D002176:Candida albicans / Q000187:drug effects / Q000201:enzymology*; D002934:Cinnamates / Q000494:pharmacology; D053630:Depsides / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005656:Fungal Proteins / Q000037:antagonists & inhibitors*; D008826:Microbial Sensitivity Tests; D000097123:Rosmarinic Acid
D000935:Antifungal Agents; D047310:Apigenin; D002109:Caffeic Acids; D002934:Cinnamates; D053630:Depsides; D004791:Enzyme Inhibitors; D005656:Fungal Proteins; D000097123:Rosmarinic Acid; C040048:caffeic acid