Three new indolyl diketopiperazine metabolites from the antarctic soil-derived fungus Penicillium sp. SCSIO 05705

Abstract

Three new indolyl diketopiperazine derivatives, penillines A and B (1 and 3), isopenilline A (2), together with seven known alkaloid compounds (E)-3-(1H-imidazole-4-yimethylene)-6-(1H-indl-3-ylmethyl)-2,5-piperazinediol (4), penilloid A (5), meleagrin (6), neoxaline (7), questiomycin A (8), N-(2-hydroxyphenyl)-acetamide (9), 2-benzoxazolinone (10), were isolated from the Antarctic soil-derived fungus Penicillium sp. SCSIO 05705. The new structures of 1–3 were elucidated on the basis of 1D and 2D NMR, mass spectra, CD spectra, and quantum chemical calculations. All the isolated compounds were tested for their antiviral (H1N1 and H3N2), antituberculosis, antibacterial, and cytotoxic activities. Among them, compounds 6–8 had significant in vitro cytotoxicities against the K562, MCF-7, A549, U937, Hela, DU145, HL60, and HT29 cell lines, with IC₅₀ values ranging from 2.73 to 17.7 μM. In addition, compound 8 showed potent antituberculosis activity with an MIC value of 3.91 μM, and the inhibition effect was close to the positive control INH (isoniazid, MIC 2.04 μM). A possible biogenesis pathway for compounds 1–7 was proposed.