Discovery of Balasubramide Derivative with Tissue-Specific Anti-Inflammatory Activity Against Acute Lung Injury by Targeting VDAC1.

ABSTRACT: Macrophage-mediated inflammatory responses including pyroptosis are involved in the pathogenesis of sepsis and acute lung injury (ALI), for which there are currently no effective therapeutic treatments. The natural product (+)-Balasubramide is an eight-membered lactam compound extracted from the leaves of the Sri Lanka plant Clausena Indica and has shown anti-inflammatory activities, but its poor pharmacokinetic properties limit its further application for ALI. In this study, a compound (+)3C-20 is discovered with improved both pharmacokinetic properties and anti-inflammatory activity from a series of (+)-Balasubramide derivatives. The compound (+)3C-20 exhibits a markedly enhanced inhibitory effect against LPS-induced expressions of pro-inflammatory factors in mouse macrophages and human

SUBMITTER: Song JQ 

PROVIDER: S-EPMC11672292 | biostudies-literature | 2024 Dec

REPOSITORIES: biostudies-literature