Identification of a quinazoline alkaloid produced by Penicillium vinaceum, an endophytic fungus from Crocus sativus

Context: Endophytic fungi are microorganisms living within the tissues of host plants, and have proven to be rich sources of biologically active secondary metabolites and therefore have attracted increasing attention in recent years. Objective: To isolate and characterize bioactive constituents from the endophytic fungus cultures of Crocus sativus Linn. (Iridaceae). Materials and methods: Endophytes were isolated from the corm of C. sativus. Endophytic fungus cultures were subjected to repeated column chromatography. Chemical structure was elucidated based on extensive spectroscopic methods and X-ray diffraction analysis. Several pathogenic fungi isolates and tumor cell lines were employed to evaluate the antifungal and cytotoxic activities of the isolated compound. Results: An isolate of Penicillium vinaceum (strain no. X17) was obtained from the corm of C. sativus. Chemical investigations of the endophyte culture broth afforded an unique quinazoline alkaloid (1), identified as (-)-(1R,4R)-1,4-(2,3)-indolmethane-1-methyl-2,4-dihydro-1H-pyrazino-[2,1-b]-quinazoline-3,6-dione, which showed cytotoxic (IC50 range 40.55-76.83 mu g/mL) and antifungal (MIC 80 range 16-64 mu g/mL) activities. Discussion and conclusions: Endophytes in C. sativus can be a rich source of novel bioactive compounds, which prompts us to expand the medicinal resource of this valuable plant in another way. Compound 1 exhibited potential cytotoxic and antifungal activities and may be considered a lead compound for promising antifungal and anticariogenic agent.