Pesimquinolones I-S, eleven new quinolone alkaloids produced by Penicillium simplicissimum and their inhibitory activity on NO production

Chong Dai; Xiaoxin Li; Kailin Zhang; Xiao-Nian Li; Wenjing Wang; Yi Zang; Xia Chen; Qin Li; Mengsha Wei; Chunmei Chen; Hucheng Zhu; Yonghui Zhang

doi:10.1016/j.bioorg.2021.104635

Pesimquinolones I-S, eleven new quinolone alkaloids produced by Penicillium simplicissimum and their inhibitory activity on NO production

Bioorg Chem. 2021 Mar:108:104635. doi: 10.1016/j.bioorg.2021.104635. Epub 2021 Jan 8.

Authors

Chong Dai¹, Xiaoxin Li¹, Kailin Zhang², Xiao-Nian Li³, Wenjing Wang¹, Yi Zang¹, Xia Chen¹, Qin Li¹, Mengsha Wei¹, Chunmei Chen¹, Hucheng Zhu⁴, Yonghui Zhang⁵

Affiliations

¹ Hubei Key Laboratory of Natural Medicinal Chemistry and Resource Evaluation, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, People's Republic of China.
² Hubei Key Laboratory of Natural Medicinal Chemistry and Resource Evaluation, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, People's Republic of China; Hubei Hualong Bio-Chemical Pharmaceutical Limited Company, Xiaogan 432800, People's Republic of China.
³ State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming 650204, People's Republic of China.
⁴ Hubei Key Laboratory of Natural Medicinal Chemistry and Resource Evaluation, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, People's Republic of China. Electronic address: zhuhucheng@hust.edu.cn.
⁵ Hubei Key Laboratory of Natural Medicinal Chemistry and Resource Evaluation, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, People's Republic of China. Electronic address: zhangyh@mails.tjmu.edu.cn.

PMID: 33484940
DOI: 10.1016/j.bioorg.2021.104635

Abstract

Eleven undescribed quinolone alkaloids, pesimquinolones I-S (1-4 and 6-12), as well as eleven known congeners (5 and 13-22), were isolated from the solid culture broth of the fungus Penicillium simplicissimum. Their chemical structures with absolute configurations were established by a combination of NMR spectroscopy, single-crystal X-ray crystallography, and modified Mosher's methods. Pesimquinolones I-K (1-3) represent the first examples of natural occurring quinolone alkaloids that possess a 6/6/6/6 tetracyclic ring system. The anti-inflammatory activities of selected compounds on LPS-induced nitric oxide (NO) production in adherent cells were evaluated. Compounds 1 and 2 showed suppressive effects on the production of NO, with IC₅₀ values of 10.13 and 8.10 μM, respectively.

Keywords: Penicillium simplicissimum; Quinolone alkaloids; inhibitory activity on NO production.

Publication types

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

MeSH terms

Alkaloids / chemistry
Alkaloids / isolation & purification
Alkaloids / pharmacology*
Animals
Anti-Inflammatory Agents / chemistry
Anti-Inflammatory Agents / isolation & purification
Anti-Inflammatory Agents / pharmacology*
Crystallography, X-Ray
Dose-Response Relationship, Drug
Lipopolysaccharides / antagonists & inhibitors
Lipopolysaccharides / pharmacology
Mice
Models, Molecular
Molecular Structure
Nitric Oxide / antagonists & inhibitors*
Nitric Oxide / biosynthesis
Penicillium / chemistry*
Quinolones / chemistry
Quinolones / isolation & purification
Quinolones / pharmacology*
RAW 264.7 Cells
Structure-Activity Relationship

Substances

Alkaloids
Anti-Inflammatory Agents
Lipopolysaccharides
Quinolones
Nitric Oxide

Supplementary concepts

Penicillium simplicissimum