title: Coumarin Antifungal Lead Compounds from Millettia thonningii and Their Predicted Mechanism of Action.
abstract: Fungal pathogens continue to pose challenges to humans and plants despite efforts to control them. Two coumarins, robustic acid and thonningine-C isolated fromMillettia thonningii, show promising activity against the fungusCandida albicanswith 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.
authors.affiliation: School of Chemical Sciences, University of Auckland, 23 Symonds Street, 1142 Auckland, New Zealand. dayi479@aucklanduni.ac.nz.|Department of Chemistry, University of Ghana, LG 56, Legon-Accra, Ghana. dayi479@aucklanduni.ac.nz.
authors.forename: Daniel M
authors.initials: DM
authors.lastname: Ayine-Tora
authors.affiliation: Department of Chemistry, University of Ghana, LG 56, Legon-Accra, Ghana. kadabohs@yahoo.com.
authors.forename: Robert
authors.initials: R
authors.lastname: Kingsford-Adaboh
authors.affiliation: Department of Chemistry, University of Ghana, LG 56, Legon-Accra, Ghana. waasoman@ug.edu.gh.
authors.forename: William A
authors.initials: WA
authors.lastname: Asomaning
authors.affiliation: Department of Chemistry, University of Ghana, LG 56, Legon-Accra, Ghana. harriebow@gmail.com.
authors.forename: Jerry J E K
authors.initials: JJ
authors.lastname: Harrison
authors.affiliation: Department of Biochemistry and Biotechnology, Kwame Nkrumah University of Science and Technology, Kumasi, Ghana. mirobfc2002@yahoo.com.
authors.forename: Felix C
authors.initials: FC
authors.lastname: Mills-Robertson
authors.affiliation: Botany Department, University of Ghana, LG 55, Legon-Accra, Ghana. sparrowson@yahoo.com.
authors.forename: Yahaya
authors.initials: Y
authors.lastname: Bukari
authors.affiliation: Department of Chemistry, University of Ghana, LG 56, Legon-Accra, Ghana. poskeydinho@yahoo.com.
authors.forename: Patrick O
authors.initials: PO
authors.lastname: Sakyi
authors.affiliation: Centre for Plant Medicine Research, 73, Mampong-Akuapem, Ghana. slykmt@yahoo.co.uk.
authors.forename: Sylvester
authors.initials: S
authors.lastname: Kaminta
authors.affiliation: School of Chemical Sciences, University of Auckland, 23 Symonds Street, 1142 Auckland, New Zealand. j.reynisson@auckland.ac.nz.
authors.forename: Jóhannes
authors.initials: J
authors.lastname: Reynisson
mesh_terms: D000935:Antifungal Agents / Q000737:chemistry / Q000494:pharmacology*; D002176:Candida albicans / Q000187:drug effects*; D020134:Catalytic Domain / Q000187:drug effects; D003374:Coumarins / Q000737:chemistry / Q000494:pharmacology*; D005656:Fungal Proteins / Q000737:chemistry / Q000378:metabolism; D007529:Isoflavones / Q000737:chemistry / Q000494:pharmacology; D008826:Microbial Sensitivity Tests; D033641:Millettia / Q000737:chemistry*; D008958:Models, Molecular; D062105:Molecular Docking Simulation; D015394:Molecular Structure; D011485:Protein Binding; D058886:Sterol 14-Demethylase / Q000737:chemistry* / Q000378:metabolism; D013329:Structure-Activity Relationship
chemical_list: D000935:Antifungal Agents; D003374:Coumarins; D005656:Fungal Proteins; D007529:Isoflavones; C105206:robustic acid; D058886:Sterol 14-Demethylase
keywords: CYP51; Candida albicans; Sclorotium; isoflavone; molecular modelling; natural products