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United States Department of Agriculture

Agricultural Research Service

Research Project: DISCOVERY AND DEVELOPMENT OF NATURAL PRODUCT FOR PHARMACEUTICAL AND AGRICHEMICAL APPLICATIONS Title: Bioactive 1 4-Dihydroxy-5-phenyl-2-pyridinone alkaloids from Septoria pistaciarum

Authors
item Kumarihamy, Mallika -
item Fronczek, Frank -
item Ferreira, Daneel -
item Jacob, Melissa -
item Khan, Shabana -
item Nanayakkara, Dhammika N.P. -

Submitted to: Journal of Natural Products
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: May 27, 2010
Publication Date: June 15, 2010
Citation: Kumarihamy, M., Fronczek, F.R., Ferreira, D., Jacob, M., Khan, S.I., Nanayakkara, D. 2010. Bioactive 1, 4-Dihydroxy-5-phenyl-2-pyridinone alkaloids from Septoria pistaciarum. Journal of Natural Products. 73:1250-1253.

Interpretive Summary: Plant-like metabolic pathways found in the apicoplast, a chloroplast-like organelle, of Plasmodium species, have been identified as suitable targets in malaria drug discovery. A number of herbicides and phytotoxins with known molecular targets in the plastid have been evaluated for antimalarial activity. Various phytotoxins released by plant pathogenic fungi are known to inhibit metabolic pathways in the apicoplast. As part of our ongoing efforts to search for potential sources of new antimalarial compounds, we have screened a number of plant pathogenic fungi for antimalarial activity. Septoria pistaciarum (Ascomycetes) is the causative agent of Septoria leaf and fruit spot disease in pistachio in the US and Mediterranean countries. The EtOAc extract of this fungus showed potent herbicidal activity and moderate antiplasmodial activity against Plasmodium falciparum albeit with low selectivity index. No previous chemical work has been reported for this species. Bioassay-guided fractionation of the EtOAc extract led to the isolation of a new 1,4-dihydroxy-5-phenyl-2-pyridinone analogue as the active compound. Three additional new but inactive analogues of the same class were also isolated and identified. Several compounds of this class have previously been isolated from a number of fungal species and have shown antibacterial, antitumor, antifungal, and neurotrophic activities.

Technical Abstract: Four new 1,4-dihydroxy-5-phenyl-2-pyridinone alkaloids (1-4) were isolated from an EtOAc extract of a culture medium of Septoria pistaciarum. The structures of these compounds were determined by spectroscopic methods, and the absolute configuration of the major compound 1 by X-ray crystallographic analysis. Compound 1 exhibited moderate in vitro antimalarial activities against chloroquine-sensitive (D6) and -resistant (W2) strains of Plasmodium falciparum and cytotoxic activity to Vero cells. Compound 2 was moderately active against both methicillin-sensitive and methicillin-resistant strains of Staphylococcus aureus.

Last Modified: 12/25/2014