Identification of a quinazoline alkaloid produced byPenicillium vinaceum, an endophytic fungus fromCrocus sativus

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.To isolate and characterize bioactive constituents from the endophytic fungus cultures of Crocus sativus Linn. (Iridaceae).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.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 (IC(50) range 40.55-76.83 μg/mL) and antifungal (MIC(80) range 16-64 μg/mL) activities.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.