Coumarin antifungal lead compounds, predicted mechanism of action

Kingsford-Adaboh, Robert; Moscoh, Daniel; Reynisson, Johannes

Abstract

Introduction: Candida albicans is one of the most common causative fungi infection despite major efforts to control it. C. albicans has emerged as one of the main causes of morbidity and mortality in immunocompromised patients suffering from, e.g., cancer or AIDS. Drug -resistance on existing drugs calls for need for new antifungal drugs. Hence it is necessary to develop new antifungal drugs to address these emerging challenges. 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 14_-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.

Method and Results: Compounds from seedsof M.thonningii were isolated and activity investigated C. albicans. Isolation yeilded robustic acid (1), thonningine-C (2), alpinumisoflavone, O'O-dimethylalpinumisoflavone.

Citation

Kingsford-Adaboh, R., Moscoh, D., & Reynisson, J. (2017, August). Coumarin antifungal lead compounds, predicted mechanism of action. Poster presented at XXIV IUCr Congress, Hyderabad International Convention Centre, Hyderabad, India

• Presentation Conference Type: Poster
• Conference Name: XXIV IUCr Congress
• Conference Location: Hyderabad International Convention Centre, Hyderabad, India
• Start Date: Aug 21, 2017
• End Date: Aug 28, 2017
• Deposit Date: Jun 8, 2023
• Publisher: International Union of Crystallography
• DOI: https://doi.org/10.1107/s2053273317091677
• Keywords: Inorganic Chemistry; Physical and Theoretical Chemistry; Condensed Matter Physics; General Materials Science; Biochemistry; Structural Biology
• Publisher URL: https://scripts.iucr.org/cgi-bin/paper?S2053273317091677
• Additional Information: Publication: Acta Crystallographica Section A: Foundations and Advances; Content type: abstracts; Article metrics: Available; Published online: 1 December 2017; Copyright: © 2017 International Union of Crystallography