New meroterpenoids and polyketides from the endophytic fungus Paraphaeosphaeria sp. C-XB-J-1 and their anti-inflammatory and SARS-CoV-2 M inhibitory activities.

Bioorg Chem

Key Laboratory of Chemistry in Ethnic Medicinal Resources of Ministry of Education, Yunnan Minzu University, Kunming 650031, Yunnan, PR China. Electronic address:

Published: June 2024

AI Article Synopsis

  • Seven new meroterpenoids (paraphaeones A-G) and two new polyketides (paraphaeones H-I) were discovered from the endophytic fungus Paraphaeosphaeria sp. C-XB-J-1, along with eight known compounds.
  • The structures of these compounds were determined using various spectroscopy methods, and some of them (specifically compounds 1 and 7) reduced levels of lactate dehydrogenase and inhibited NLRP3 inflammasome activity.
  • Compounds 4 and 7 also demonstrated potential as inhibitors of the SARS-CoV-2 main protease, showing promising IC values that indicate their effects on viral activity.

Article Abstract

Seven new meroterpenoids, paraphaeones A-G (1-7), and two new polyketides, paraphaeones H-I (8-9), along with eight known compounds (10-17), were isolated from the endophytic fungus Paraphaeosphaeria sp. C-XB-J-1. The structures of 1-9 were identified through the analysis of H, C, and 2D NMR spectra, assisted by HR-ESI-MS data. Compounds 1 and 7 exhibited a dose-dependent decrease in lactate dehydrogenase levels, with IC values of 1.78 μM and 1.54 μM, respectively. Moreover, they inhibited the secretion of IL-1β and CASP-1, resulting in a reduction in the activity levels of NLRP3 inflammasomes. Fluorescence microscopy results indicated that compound 7 concentration-dependently attenuated cell pyroptosis. Additionally, compounds 4 and 7 showed potential inhibitory effects on the severe acute respiratory syndrome coronavirus-2 main protease (SARS-CoV-2 M), with IC values of 10.8 ± 0.9 μM and 12.9 ± 0.7 μM, respectively.

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http://dx.doi.org/10.1016/j.bioorg.2024.107315DOI Listing

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