LAUSR

Growing evidence indicates that endophytes are among the new prolific producers of bioactive natural products [1]. In our screening of antimicrobial endophytes from Edgeworthia chrysantha Lindl., a traditional Chinese medicinal plant used to treat swelling of eye, ophthalmalgia, delacrimation, nephelium of eye, and nocturnal emission [2–4], the ethyl acetate extract of the fermentation broth of the endophytic strain D exhibited strong antimicrobial activities against pathogenic Escherichia coli, Staphyloccocus aureus, and Candida albicans [5]. A follow-up bioassay-guided fractionation led to the isolation of five heterocyclic alkaloids (1–5) with potent antimicrobial activities. The mixed metabolic products of the fermentation broth of A. fumigatus D were obtained through liquid-liquid extraction using ethyl acetate and subjected to flash fractionation on a preparative HPLC column to yield six fractions (F0–F5). Antimicrobial assay indicated that fractions F2 and F3 exhibited impressive inhibitory effects on all tested pathogens at 10 mg/mL. Further isolation and purification on HPLC reversed-phase columns finally led to the isolation of five secondary metabolites from fractions F2 and F3. On basis of spectroscopic data (1H NMR and ESI-MS) and comparison with literature data (Table 1), these compounds were respectively characterized as bisdethiobis(methylthio)gliotoxin (1) [6], gliotoxin (2) [7], pseurotin A (3) [8], and spirotryprostatins A (4) [9] and G (5) [10]. Bioassay results indicated that these heterocyclic alkaloids 1–5 had impressive antimicrobial activities against three human pathogenic microbes (Table 2), E. coli, S. aureus, and C. albicans. Bisdethiobis(methylthio)gliotoxin (1) and spirotryprostatin G (5) exhibited the strongest inhibitory effect on C. albicans with the same MIC values of 0.39 g·mL–1. Pseurotin A (3) and spirotryprostatin A (4) also had the best antimicrobial activities against S. aureus with the same MIC of 0.39 g·mL–1. Compound 4 also showed the strongest antibacterial activity against E. coli with an MIC value of 0.39 g·mL–1. This is the first report on the antimicrobial activity of spirotryprostatins A (4) and G (5).