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

• Published in: Bioorganic chemistry 2024-06, Vol.147, p.107315
• Main Authors: Li, Qi, Yang, Peng-Yun, Peng, Chao, Zhang, Xing-Jie, Jiang, Yun-Tao, Li, Yan-Ping, Gao, Lu
• Format: Article
• Language: English
• Subjects: Animals; Anti-Inflammatory Agents - chemistry; Anti-Inflammatory Agents - isolation & purification; Anti-Inflammatory Agents - pharmacology; Anti-Inflammatory Agents, Non-Steroidal - chemistry; Anti-Inflammatory Agents, Non-Steroidal - isolation & purification; Anti-Inflammatory Agents, Non-Steroidal - pharmacology; Antiviral Agents - chemistry; Antiviral Agents - isolation & purification; Antiviral Agents - pharmacology; Ascomycota - chemistry; Coronavirus 3C Proteases - antagonists & inhibitors; Coronavirus 3C Proteases - chemistry; Coronavirus 3C Proteases - metabolism; COVID-19 Drug Treatment; Dose-Response Relationship, Drug; Humans; Molecular Structure; Polyketides - chemistry; Polyketides - isolation & purification; Polyketides - pharmacology; SARS-CoV-2 - drug effects; Structure-Activity Relationship; Terpenes - chemistry; Terpenes - isolation & purification; Terpenes - pharmacology
• ISSN: 1090-2120
• DOI: 10.1016/j.bioorg.2024.107315

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.