Biopharmaceutics, Guangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou 510515, China.
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.
Bioorg Chem. 2021 Jul;112:104927. doi: 10.1016/j.bioorg.2021.104927. Epub 2021 Apr 20.
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 Mo(OAc)-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) value of 6.2 μM, demonstrated 6 could act as a new potential LXR agonist.
四种新的色烯衍生物，即 pestalotiochromenoic 酸 A-D（1、2、4 和 5），以及两种新的色酮衍生物，即 pestalotiochromones A 和 B（6 和 7），从海洋藻类来源的真菌 Pestalotiopsis neglecta SCSIO41403 中分离得到，此外还有一种报道的衍生物，命名为 piperochromenoic 酸（3），其构型首次确定。它们的结构通过详细的核磁共振（NMR）和质谱分析确定，而绝对构型则通过理论 NMR 和电子圆二色性（ECD）计算，包括 Mo(OAc)-诱导的 ECD 实验确定。这些色烯和色酮衍生物表现出微弱的细胞毒性，但通过体外测试 LXRα、LXRβ 及其靶基因 ABCA1 的表达，以及计算机对接分析，显示出明显的肝 X 受体（LXRs）调节活性。此外，表面等离子体共振（SPR）实验显示 pestalotiochromone A（6）与 LXRα 之间具有较高的结合亲和力，解离平衡常数（K）值为 6.2 μM，表明 6 可以作为一种新的潜在 LXR 激动剂。
