Coumarin Antifungal Lead Compounds from Millettia thonningii and Their Predicted Mechanism of Action

Reynisson

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 14a-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.

Citation

Reynisson. (2016). Coumarin Antifungal Lead Compounds from Millettia thonningii and Their Predicted Mechanism of Action. Molecules, https://doi.org/10.3390/molecules21101369

• Acceptance Date: Oct 6, 2016
• Publication Date: Oct 15, 2016
• Journal: Molecules
• Publisher: MDPI
• DOI: https://doi.org/10.3390/molecules21101369
• Keywords: CYP51, Candida albicans, Sclorotium, isoflavone, molecular modelling, natural products, Antifungal Agents, Catalytic Domain, Coumarins, Fungal Proteins, Isoflavones, Microbial Sensitivity Tests, Millettia, Models, Molecular, Molecular Docking Simulation, Molecular Structure, Protein Binding, Sterol 14-Demethylase, Structure-Activity Relationship
• Publisher URL: http://doi.org/10.3390/molecules21101369