Fused-ring α-pyrones from intramolecular C-H activation and their lipids-lowering activity associated with LXR-IDOL-LDLR axis regulation
- PMID: 36368255
- DOI: 10.1016/j.ejmech.2022.114866
Fused-ring α-pyrones from intramolecular C-H activation and their lipids-lowering activity associated with LXR-IDOL-LDLR axis regulation
Abstract
Lipids-lowering is considered as the most effective approach to decrease the risk of Atherosclerotic cardiovascular disease (ASCVD), of which atherosclerosis is the most common cause. Natural products containing a unique type of α-pyrone was reported to suppress atherosclerosis in which α-pyrone might be considered as an important pharmacore. In this study, an efficient one-pot intramolecular C-H activation strategy was applied to the synthesis of potentially bioactive α-pyrone derivatives. As the result, three different scaffolds were quickly and conveniently generated, including thiophenes, pyrrole and indole derivatives. Among of them, eight α-pyrone derivatives showed potential effects to promote the uptake of LDL in HepG2 cells. Active unique α-pyrones compounds exhibiting potent in vitro and in vivo lipids-lowering effects, and a novel mechanism associated with the regulation of LXR-IDOL-LDLR axis, the new pathway targeted pharmacologically to control plasma cholesterol levels, were disclosed firstly in this study.
Keywords: C–H activation; In vivo lipids-lowering effect; LDL uptaking; LXR-IDOL-LDLR axis; One-pot intramolecular cyclization; α-Pyrone derivatives.
Copyright © 2022 Elsevier Masson SAS. All rights reserved.
Conflict of interest statement
Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
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