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

Abstract

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).

GRAPHICAL ABSTRACT

Keywords:

• Marine fungi
• 2,5-diketopiperazine
• antibacterial
• quorum sensing

Acknowledgements

The authors gratefully thank Dr. Buddha (Zhejiang University of Technology) for polishing the language. In addition, the authors thank David C. Rowley at the College of Pharmacy, University of Rhode Island for kind assistance.

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

This work was financially supported by the programs of the National Key Research and Development Program of China [No. 2022YEC2804104], the National Natural Science Foundation of China [No. 42276137], the Key Research and Development Program of Zhejiang Province [2021C03084].