Discovery of 2,5-diketopiperazine alkaloids with quorum sensing inhibitory activity from the marine fungus Penicillium sp. ZJUT-34

One new 2,5-DKP derivative O-dihydroxycyclopenol (1) and seven known congeners 2-8 were isolated from the marine fungus Penicillium sp. ZJUT-34 cultured on rice medium. The planar structure of 1 was established by extensive spectroscopic analysis, including 1D, 2D NMR and HR-ESI-MS, while the relative configuration of 1 was determined by quantum chemical calculation. In the QS inhibitory assay, 1 significantly inhibited the production of violacein in Chromobacterium violaceum ATCC12472 (20.65%) at a concentration of 6.25 μg/mL without affecting the growth of the strain, as compared with norharmane (22.14%), a quorum sensing inhibitor (QSI) identified in our previous study. It represented the first report on the QS inhibitory activity of the seven-membered 2,5-DKPs. In addition, compounds 1-8 were subjected to antibacterial assay against six pathogenic bacteria Compound 8 exhibited comparable antibacterial activity against Enterococcus faecalis FA2-2 (MIC = 96 μg/mL) with the positive control gentamicin (MIC = 80 μg/mL).