Chromene and chromone derivatives as liver X receptors modulators from a marine-derived Pestalotiopsis neglecta fungus

Zhi Liang; Tanwei Gu; Jianjiao Wang; Jianglian She; Yuxiu Ye; Wenyu Cao; Xiaowei Luo; Jiao Xiao; Yonghong Liu; Lan Tang; Xuefeng Zhou

doi:10.1016/j.bioorg.2021.104927

Chromene and chromone derivatives as liver X receptors modulators from a marine-derived Pestalotiopsis neglecta fungus

Bioorg Chem. 2021 Jul:112:104927. doi: 10.1016/j.bioorg.2021.104927. Epub 2021 Apr 20.

Authors

Zhi Liang¹, Tanwei Gu¹, Jianjiao Wang², Jianglian She³, Yuxiu Ye⁴, Wenyu Cao¹, Xiaowei Luo⁴, Jiao Xiao⁵, Yonghong Liu³, Lan Tang⁶, Xuefeng Zhou⁷

Affiliations

¹ Biopharmaceutics, Guangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou 510515, China.
² CAS Key Laboratory of Tropical Marine Bio-resources and Ecology, Guangdong Key Laboratory of Marine Materia Medica, Innovation Academy of South China Sea Ecology and Environmental Engineering, and South China Sea Institute of Oceanology, Chinese Academy of Sciences, Guangzhou 510301, China.
³ CAS Key Laboratory of Tropical Marine Bio-resources and Ecology, Guangdong Key Laboratory of Marine Materia Medica, Innovation Academy of South China Sea Ecology and Environmental Engineering, and South China Sea Institute of Oceanology, Chinese Academy of Sciences, Guangzhou 510301, China; Southern Marine Science and Engineering Guangdong Laboratory (Guangzhou), Guangzhou 511458, China.
⁴ Institute of Marine Drugs, Guangxi University of Chinese Medicine, Nanning 530200, China.
⁵ Wuya College of Innovation, Shenyang Pharmaceutical University, Shenyang 110016, China.
⁶ Biopharmaceutics, Guangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou 510515, China. Electronic address: tl405@smu.edu.cn.
⁷ CAS Key Laboratory of Tropical Marine Bio-resources and Ecology, Guangdong Key Laboratory of Marine Materia Medica, Innovation Academy of South China Sea Ecology and Environmental Engineering, and South China Sea Institute of Oceanology, Chinese Academy of Sciences, Guangzhou 510301, China; Southern Marine Science and Engineering Guangdong Laboratory (Guangzhou), Guangzhou 511458, China. Electronic address: xfzhou@scsio.ac.cn.

PMID: 33932772
DOI: 10.1016/j.bioorg.2021.104927

Abstract

Four new chromene derivatives, pestalotiochromenoic acids A - D (1, 2, 4, and 5), and two new chromone derivatives, pestalotiochromones A and B (6 and 7), were obtained from the marine alga-derived fungus Pestalotiopsis neglecta SCSIO41403, as well as a reported derivate named piperochromenoic acid (3) with its configuration determined for the first time. Their structures were determined by detailed nuclear magnetic resonance (NMR) and mass spectroscopic analyses, while the absolute configurations were established by theoretical NMR and electronic circular dichroism (ECD) calculation, including Mo₂(OAc)₄-induced ECD experiments. Those chromene and chromone derivatives displayed weak cytotoxicity, but showed obvious liver X receptors (LXRs) modulatory activities, by in vitro tests on the expression of LXRα, LXRβ and theirtarget gene ABCA1, as well as in silico docking analysis. Moreover, the high binding affinities between pestalotiochromone A (6) and LXRα, revealed by surface plasmon resonance (SPR) with the dissociation equilibrium constant (K_D) value of 6.2 μM, demonstrated 6 could act as a new potential LXR agonist.

Keywords: Chromene; Chromone; Liver X receptors; Marine derived fungus; Pestalotiopsis neglecta.

Publication types

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

MeSH terms

Cell Line, Tumor
Cell Survival / drug effects
Chromones / chemistry
Chromones / isolation & purification
Chromones / pharmacology*
Dose-Response Relationship, Drug
Humans
Liver X Receptors / genetics
Liver X Receptors / metabolism*
Molecular Structure
Neglecta / chemistry*
Structure-Activity Relationship

Substances

Chromones
Liver X Receptors