Abstract
Fungal pathogens continue to pose challenges to humans and plants despite efforts to control them. Two coumarins, robustic acid and thonningine-C isolated from Millettia thonningii, show promising activity against the fungus Candida albicans with minimum fungicidal concentration of 1.0 and 0.5 mg/mL, respectively. Molecular modelling against the putative bio-molecular target, lanosterol 14α-demethylase (CYP51), revealed a plausible binding mode for the active compounds, in which the hydroxyl group binds with a methionine backbone carboxylic group blocking access to the iron catalytic site. This binding disrupts the synthesis of several important sterols for the survival of fungi.
Highlights
Candida albicans is one of the most common fungal pathogens causing infection despite major efforts to control it [1,2]
The seeds of Milletia thonningii were collected from the University of Ghana campus
Previous studies have focused on azoles, polyenes, griseofulvin, flucytosine and allylamine molecular scaffolds for antifungal design, e.g., the clinically used drugs voriconazole, ketoconazole and fluconazole are derived from azole containing molecules and terbinafine from allylamine [10]
Summary
Candida albicans is one of the most common fungal pathogens causing infection despite major efforts to control it [1,2]. C. albicans has emerged as one of the main causes of morbidity and mortality in immunocompromised patients suffering from diseases such as cancer or AIDS [3,4,5,6]. There are a number of drugs such as flucoconazole, nystatin, voriconazole, terbinafine and echinocandin to address fungal infections [10]. Drug resistance, restricted systemic usage due to dose-related toxicity and the emergence of new strains of fungal infections all undermine the efficacy of these drugs [11,12,13,14,15]. It is necessary to develop new antifungal treatments to address these emerging challenges
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