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

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.