Work

Design and Synthesis of Novel Purine Analogues as Potential IL‐1β Inhibitors Targeting Vascular Inflammation

Year: 2026

Type: article

Abstract: ABSTRACT Proinflammatory cytokine interleukin (IL)‐1β is a key mediator of the inflammatory response in atherosclerosis. Targeting IL‐1β represents a new approach for the anti‐inflammatory therapy of cardiovascular diseases. Based on our previous data demonstrating that cardioprotective 6‐piperazinyl purines can effectively inhibit IL‐1β release in vascular cells, in this study, we present the synthesis of a next generation of purine analogues bearing either a furoxan moiety as a nitric oxide (NO) donor, or a (methylsulfonyl)thio group, a benzothioamide, or a 5‐phenyl‐3H‐1,2‐dithiole‐3‐thione as putative hydrogen sulfide (H 2 S) donor moieties. NO and H 2 S are gaseous signaling molecules that can reduce vascular inflammation. The new purine analogues were evaluated for their anti‐inflammatory activity by assessing their inhibitory effect on the secretion of lipopolysaccharide (LPS)‐induced IL‐1β in human aortic smooth muscle cells (HAoSMCs). Our initial findings revealed that compounds bearing a [methylsulfonyl)thio]propanoyl or [methylsulfonyl)thio]hexanoyl group (compounds MK175 and MK169 , respectively) could effectively inhibit LPS‐induced IL‐1β release in HAoSMCs.

Source: Chemistry & Biodiversity

DOI: 10.1002/cbdv.202502588