Submitted to: Journal of Natural Products
Publication Type: Peer reviewed journal
Publication Acceptance Date: 4/17/2013
Publication Date: 5/9/2013
Citation: Gao, J., Radwan, M.M., Leon, F., Dale, O.R., Husni, A.S., Wu, Y., Lupien, S.L., Wang, X., Manly, S.P., Hill, R.A., Dugan, F.M., Cutler, H.G., Cutler, S.J. 2013. Neocosmospora sp.-derived resorcylic acid lactones with in vitro binding capacity for human opioid and cannabinoid receptors. Journal of Natural Products. 76:824-828. Interpretive Summary: A fungal isolate belonging to the genus Neocosmospora (a clade in the Fusarium solani species complex) produced compounds with high in vitro binding affinity for human opioid receptors and also affinity for cannabinoid receptors. Such receptors in the human nervous system are sites for drug activity, and are of high pharmacological importance for pain relief and other effects. Detailed knowledge of the structure of compounds eliciting potential effects can serve as leads in the studies of these classes of compounds. The ultimate goal is production of additional pharmacological products. Fungi in Neocosmospora are documented elsewhere, including culture collections of USDA-ARS (NRRL).
Technical Abstract: Bioassay-guided fractionation of a fungus Neocosmospora sp. (UM-031509) resulted in the isolation of three new resorcyclic acid lactones, neocosmosin A (2), neocosmosin B (3) and neocosmosin C (4). Three known resorcylic acid lactones, monocillin IV (1), monocillin II (5) and monorden (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 (ESI-MS) 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.