1. Chromene and chromone derivatives as liver X receptors modulators from a marine-derived Pestalotiopsis neglecta fungus
- Author
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Zhi Liang, Xuefeng Zhou, Lan Tang, Jianglian She, Yuxiu Ye, Xiaowei Luo, Tanwei Gu, Jianjiao Wang, Wenyu Cao, Yonghong Liu, and Jiao Xiao
- Subjects
Circular dichroism ,Cell Survival ,Stereochemistry ,01 natural sciences ,Biochemistry ,Dissociation (chemistry) ,Structure-Activity Relationship ,chemistry.chemical_compound ,Cell Line, Tumor ,Neglecta ,Drug Discovery ,Humans ,Surface plasmon resonance ,Liver X receptor ,Cytotoxicity ,Molecular Biology ,Equilibrium constant ,Liver X Receptors ,Dose-Response Relationship, Drug ,Molecular Structure ,010405 organic chemistry ,Organic Chemistry ,In vitro ,0104 chemical sciences ,010404 medicinal & biomolecular chemistry ,chemistry ,Chromones ,Chromone - 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 their target 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 (KD) value of 6.2 μM, demonstrated 6 could act as a new potential LXR agonist.
- Published
- 2021
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