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

Qi Li; Peng-Yun Yang; Chao Peng; Xing-Jie Zhang; Yun-Tao Jiang; Yan-Ping Li; Lu Gao

doi:10.1016/j.bioorg.2024.107315

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

Bioorg Chem. 2024 Jun:147:107315. doi: 10.1016/j.bioorg.2024.107315. Epub 2024 Mar 27.

Authors

Qi Li¹, Peng-Yun Yang², Chao Peng¹, Xing-Jie Zhang², Yun-Tao Jiang³, Yan-Ping Li⁴, Lu Gao⁵

Affiliations

¹ Key Laboratory of Chemistry in Ethnic Medicinal Resources of Ministry of Education, Yunnan Minzu University, Kunming 650031, Yunnan, PR China.
² Key Laboratory of Medicinal Chemistry for Natural Resource, Ministry of Education, Yunnan Characteristic Plant Extraction Laboratory, Yunnan Key Laboratory of Research and Development for Natural Products, State Key Laboratory for Conservation and Utilization of Bio-Resources in Yunnan, School of Pharmacy and School of Chemical Science and Technology, Yunnan University, Kunming 650091, Yunnan, PR China.
³ Key Laboratory of Chemistry in Ethnic Medicinal Resources of Ministry of Education, Yunnan Minzu University, Kunming 650031, Yunnan, PR China. Electronic address: ymujyt_2018@163.com.
⁴ School of Chinese Materia Medica, Yunnan University of Chinese Medicine, Kunming 650500, Yunnan, PR China. Electronic address: lyp8691@163.com.
⁵ Key Laboratory of Chemistry in Ethnic Medicinal Resources of Ministry of Education, Yunnan Minzu University, Kunming 650031, Yunnan, PR China. Electronic address: gl990@foxmail.com.

PMID: 38604017
DOI: 10.1016/j.bioorg.2024.107315

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 ¹H, ¹³C, and 2D NMR spectra, assisted by HR-ESI-MS data. Compounds 1 and 7 exhibited a dose-dependent decrease in lactate dehydrogenase levels, with IC₅₀ 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^pro), with IC₅₀ values of 10.8 ± 0.9 μM and 12.9 ± 0.7 μM, respectively.

Keywords: Anti-inflammatory activity; Meroterpenoids; Paraphaeosphaeria sp. C-XB-J-1; Polyketides; SARS-CoV-2 M(pro) inhibitory.

MeSH terms

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
COVID-19 Drug Treatment
Coronavirus 3C Proteases* / antagonists & inhibitors
Coronavirus 3C Proteases* / chemistry
Coronavirus 3C Proteases* / metabolism
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

Substances

3C-like proteinase, SARS-CoV-2