Neocosmospora sp.-Derived Resorcylic Acid Lactones with in Vitro Binding Affinity for Human Opioid and Cannabinoid Receptors

• Published in: Journal of natural products (Washington, D.C.) D.C.), 2013-05, Vol.76 (5), p.824-828
• Main Authors: Gao, Jiangtao, Radwan, Mohamed M, León, Francisco, Dale, Olivia Reed, Husni, Afeef S, Wu, Yunshan, Lupien, Shari, Wang, Xiaoning, Manly, Susan P, Hill, Robert A, Dugan, Frank M, Cutler, Horace G, Cutler, Stephen J
• Format: Article
• Language: English
• Subjects: Crystallography, X-Ray; Electron Spin Resonance Spectroscopy; Georgia; HEK293 Cells; Humans; Hypocreales - chemistry; Lactones - chemistry; Lactones - isolation & purification; Lactones - pharmacology; Molecular Conformation; Molecular Structure; Receptors, Cannabinoid - drug effects; Receptors, Opioid - drug effects; Resorcinols - chemistry; Resorcinols - isolation & purification; Resorcinols - pharmacology
• ISSN: 0163-3864; 1520-6025
• DOI: 10.1021/np300653d

Bioassay-guided fractionation of a fungus Neocosmospora sp. (UM-031509) resulted in the isolation of three new resorcylic acid lactones, neocosmosin A (2), neocosmosin B (3), and neocosmosin C (4). Three known resorcylic acid lactones, monocillin IV (1), monocillin II (5), and radicicol (6), were also isolated and identified. The structures of these compounds were established on the basis of extensive 1D and 2D NMR spectroscopic analysis, mass spectrometric (ESIMS) data, and X-ray crystallography. Compounds 4–6 show good binding affinity for the human opioid receptors. These findings have important implications for evaluating the potential psychoactive effects with this class of compounds.