Entonalactams A–C: Isoindolinone derivatives from an Australian rainforest fungus belonging to the genus Entonaema. (September 2015)

• Record Type: Journal Article
• Authors: Choomuenwai, Vanida; Beattie, Karren D.; Healy, Peter C.; Andrews, Katherine T.; Fechner, Nigel; Davis, Rohan A.
• Is Part Of: Phytochemistry. Volume 117(2015:Sep.)
• Page Start: 10
• Page End: 16
• Publication Date: 2015-09
• Subjects: AHJKTCDLDHRZMO-UHFFFAOYSA-N -- PXAGUFKQQFOQDV-UHFFFAOYSA-N -- YGJCXQFOBXGSDS-UHFFFAOYSA-N; Entonaema -- Isoindolinone -- Lactam -- Entonalactam -- Rainforest -- Fungi -- Natural product -- Malaria; Botanical chemistry -- Periodicals; Biochemistry -- Periodicals; Botany -- Periodicals; Chimie végétale -- Périodiques; 572.2
• DOI: 10.1016/j.phytochem.2015.05.018
• Languages: English
• ISSNs: 0031-9422

Abstract

Graphical abstract: Bioassay-guided fractionation of an anti-malarial extract derived from the Australian rainforest fungus Entonaema sp. resulted in the isolation and characterisation of three new isoindolinone derivatives, entonalactams A–C. Highlights: A unique Australian-sourced fungi collection was screened for antimalarial activity. 3 new isoindolinones (entonalactams A–C) and 3 known natural products were isolated. The chemical structures of entonalactams A–C were determined via NMR/MS data analysis. A single crystal X-ray structure for entonalactam A was obtained. All isolated compounds exhibited low activity against Plasmodium falciparum at 50 μM. Abstract: Bioassay-guided fractionation of an antimalarial DCM/MeOH extract derived from the Australian rainforest fungus Entonaema sp. resulted in the isolation of three new isoindolinone derivatives, entonalactams A–C (1 –3 ), along with the known natural products 3-methoxy-5-methylbenzene-1, 2-diol (4 ), daldinal B (5 ), and ergosta-4, 6, 8(14), 22-tetraen-3-one (6 ). The chemical structures of the new secondary metabolites were determined following extensive 1D/2D NMR and MS data analysis. A single crystal X-ray structure for entonalactam A (1 ) confirmed the NMR-based structure assignment. Entonalactams A–C (1–3 ) were all determined to be racemic based on chiro-optical data. All secondary metabolites were tested in vitro against Plasmodium falciparum malaria parasites, and ergosta-4, 6, 8(14), 22-tetraen-3-one (6 ) was identified as the most active compound with 66% inhibition at 50 μM.