Clavipyrrine A, a unique polycyclic nitrogenous meroterpenoid with promising anti-glioma effects isolated from the fungus Clitocybe clavipes

Zhaocui Sun; Deli Chen; Lingyu Li; Yong Hou; Meiying Chen; Guodong Huang; Guoxu Ma; Zongyang Li

doi:10.1016/j.bioorg.2021.105468

Clavipyrrine A, a unique polycyclic nitrogenous meroterpenoid with promising anti-glioma effects isolated from the fungus Clitocybe clavipes

Bioorg Chem. 2021 Dec:117:105468. doi: 10.1016/j.bioorg.2021.105468. Epub 2021 Nov 5.

Authors

Zhaocui Sun¹, Deli Chen², Lingyu Li¹, Yong Hou¹, Meiying Chen¹, Guodong Huang³, Guoxu Ma⁴, Zongyang Li⁵

Affiliations

¹ Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences & Peking Union Medical College, No. 151, Malianwa North Road, Haidian District, Beijing 100193, China.
² Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences & Peking Union Medical College, No. 151, Malianwa North Road, Haidian District, Beijing 100193, China; Hainan Branch of Institute of Medicinal Plant Development, Chinese Academy of Medicinal Sciences & Peking Union Medical College (Hainan Provincial Key Laboratory of Resources Conservation and Development of Southern Medicine), Haikou 570311, China.
³ Department of Neurosurgery, Shenzhen Key Laboratory of Neurosurgery, the First Affiliated Hospital of Shenzhen University, Shenzhen Second People's Hospital, 3002# Sungang Road, Futian District, Shenzhen 518035, China.
⁴ Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences & Peking Union Medical College, No. 151, Malianwa North Road, Haidian District, Beijing 100193, China; Department of Neurosurgery, Shenzhen Key Laboratory of Neurosurgery, the First Affiliated Hospital of Shenzhen University, Shenzhen Second People's Hospital, 3002# Sungang Road, Futian District, Shenzhen 518035, China; Hainan Branch of Institute of Medicinal Plant Development, Chinese Academy of Medicinal Sciences & Peking Union Medical College (Hainan Provincial Key Laboratory of Resources Conservation and Development of Southern Medicine), Haikou 570311, China. Electronic address: mgxfl8785@163.com.
⁵ Department of Neurosurgery, Shenzhen Key Laboratory of Neurosurgery, the First Affiliated Hospital of Shenzhen University, Shenzhen Second People's Hospital, 3002# Sungang Road, Futian District, Shenzhen 518035, China. Electronic address: lizong1028@126.com.

PMID: 34768204
DOI: 10.1016/j.bioorg.2021.105468

Abstract

Clavipyrrine A (1), a novel polycyclic nitrogenous meroterpenoid with a pyrrolo[1,2-a]imidazole and a 10-membered carbocycle fused with an α,β-epoxy-γ-lactone, was isolated from Clitocybe clavipes, a basidiomycete. X-ray crystallography and spectroscopic analysis were used to fully elucidate its structure. The biosynthetic origin of the pyrrole unit in this nitrogenous meroterpenoid was identified by incorporating ¹⁵N-labeled γ-aminobutyric acid. Compound 1 displayed promising anti-glioma activities and induced glioma cell apoptosis through inhibiting the JAK/STAT3 pathway and reinforcing SOCS1/3.

Keywords: Anti-glioma activities; Clavipyrrine A; Clitocybe clavipes; JAK/STAT3 pathway; Meroterpenoid.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Agaricales / chemistry*
Antineoplastic Agents / chemistry
Antineoplastic Agents / isolation & purification
Antineoplastic Agents / pharmacology*
Apoptosis / drug effects
Cell Line, Tumor
Cell Survival / drug effects
Crystallography, X-Ray
Dose-Response Relationship, Drug
Glioma / drug therapy*
Glioma / metabolism
Humans
Janus Kinases / antagonists & inhibitors
Janus Kinases / metabolism
Models, Molecular
Molecular Structure
STAT3 Transcription Factor / antagonists & inhibitors
STAT3 Transcription Factor / metabolism
Structure-Activity Relationship

Substances

Antineoplastic Agents
STAT3 Transcription Factor
STAT3 protein, human
Janus Kinases

Supplementary concepts

Ampulloclitocybe clavipes