title: Identification of a quinazoline alkaloid produced by Penicillium vinaceum, an endophytic fungus from Crocus sativus.
abstract: BACKGROUND
  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).
  
  
  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 (IC(50) range 40.55-76.83 μg/mL) and antifungal (MIC(80) range 16-64 μg/mL) activities.
  
  
  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.
authors.affiliation: Department of Pharmacognosy, School of Pharmacy, Second Military Medical University, Shanghai, PR China.
authors.forename: Cheng-Jian
authors.initials: CJ
authors.lastname: Zheng
authors.forename: Lin
authors.initials: L
authors.lastname: Li
authors.forename: Jing-ping
authors.initials: JP
authors.lastname: Zou
authors.forename: Ting
authors.initials: T
authors.lastname: Han
authors.forename: Lu-Ping
authors.initials: LP
authors.lastname: Qin
mesh_terms: D000470:Alkaloids / Q000302:isolation & purification / Q000494:pharmacology*; D000935:Antifungal Agents / Q000008:administration & dosage / Q000302:isolation & purification / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000302:isolation & purification / Q000494:pharmacology; D045744:Cell Line, Tumor; D027622:Crocus / Q000382:microbiology*; D006801:Humans; D020128:Inhibitory Concentration 50; D008826:Microbial Sensitivity Tests; D009369:Neoplasms / Q000188:drug therapy / Q000473:pathology; D010407:Penicillium / Q000302:isolation & purification / Q000378:metabolism*; D011799:Quinazolines / Q000302:isolation & purification / Q000494:pharmacology*; D014961:X-Ray Diffraction
chemical_list: C571810:(-)-(1R,4R)-1,4-(2,3)-indolmethane-1-methyl-2,4-dihydro-1H-pyrazino-(2,1-b)quinazoline-3,6-dione; D000470:Alkaloids; D000935:Antifungal Agents; D000970:Antineoplastic Agents; D011799:Quinazolines