An unprecedented ergostane with a 6/6/5 tricyclic 13(14 → 8)abeo-8,14-seco skeleton from Talaromyces adpressus

Mi Zhang; Qin Li; Shuangjun Li; Yanfang Deng; Muyuan Yu; Jinping Liu; Changxing Qi; Xiliang Yang; Hucheng Zhu; Yonghui Zhang

doi:10.1016/j.bioorg.2022.105943

An unprecedented ergostane with a 6/6/5 tricyclic 13(14 → 8)abeo-8,14-seco skeleton from Talaromyces adpressus

Bioorg Chem. 2022 Oct:127:105943. doi: 10.1016/j.bioorg.2022.105943. Epub 2022 Jun 13.

Authors

Mi Zhang¹, Qin Li², Shuangjun Li³, Yanfang Deng², Muyuan Yu², Jinping Liu³, Changxing Qi², Xiliang Yang⁴, Hucheng Zhu⁵, Yonghui Zhang⁶

Affiliations

¹ Hubei Key Laboratory of Natural Medicinal Chemistry and Resource Evaluation, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China; Department of In Vitro Diagnostic Reagent, National Institutes for Food and Drug Control (NIFDC), Beijing 100050, China.
² Hubei Key Laboratory of Natural Medicinal Chemistry and Resource Evaluation, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
³ Hubei Key Laboratory of Natural Medicinal Chemistry and Resource Evaluation, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China; Department of Pharmacy, Hubei Province Key Laboratory of Occupational Hazard Identification and Control, Institute of Infection, Immunology and Tumor Microenvironments, Medical College, Wuhan University of Science and Technology, Wuhan 430081, China.
⁴ Department of Pharmacy, Hubei Province Key Laboratory of Occupational Hazard Identification and Control, Institute of Infection, Immunology and Tumor Microenvironments, Medical College, Wuhan University of Science and Technology, Wuhan 430081, China. Electronic address: yxlyxl117@163.com.
⁵ Hubei Key Laboratory of Natural Medicinal Chemistry and Resource Evaluation, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China. Electronic address: zhuhucheng@hust.edu.cn.
⁶ Hubei Key Laboratory of Natural Medicinal Chemistry and Resource Evaluation, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China. Electronic address: zhangyh@mails.tjmu.edu.cn.

PMID: 35717801
DOI: 10.1016/j.bioorg.2022.105943

Abstract

Talasterone A (1), an unprecedented 6/6/5 tricyclic 13(14 → 8)abeo-8,14-seco-ergostane steroid, together with two known congeners dankasterone B (2) and (14β,22E)-9,14-dihydroxyergosta-4,7,22-triene-3,6-dione (3), were characterized from Talaromyces adpressus. The structure of 1 with absolute configuration was elucidated based on NMR spectroscopic data and ECD calculation. Compound 2 belongs to a class of unconventional 13(14 → 8)abeo-ergostanes, which have been renewed via the 1,2-migration of C-13-C-14 bond to C-8. In addition, compound 1 represents the first example of ergostane with a tricyclic 13(14 → 8)abeo-8,14-seco-ergostane skeleton. The proposed biosynthetic pathway was established with the support of the coisolation of the known congeners from the producing organism. It is especially noteworthy that compound 1 exhibited potent anti-inflammatory activity with an IC₅₀ value of 8.73 ± 0.66 μM, inhibiting the NF-κB pathway and thus reducing the production of proinflammatory cytokines.

Keywords: Anti-inflammatory activity; Dankasterone; NF-κB pathway; Rearranged steroid; Talaromyces adpressus.

Publication types

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

MeSH terms

Ergosterol* / analogs & derivatives
Ergosterol* / pharmacology
Molecular Structure
Skeleton
Talaromyces* / chemistry

Substances

ergostane
Ergosterol

Supplementary concepts

Talaromyces adpressus