ArticleRSC advances2026
Discovery and synthesis of phenylthiophene sulfonamide derivatives with promising anti-inflammatory activity.
Article in RSC advances, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Dysregulated inflammation is central to chronic diseases such as rheumatoid arthritis and atherosclerosis. In this study, an in-house screening assay identified L464-0189 as a promising anti-inflammatory hit. Based on the phenylthiophene sulfonamide scaffold, 31 novel compounds bearing diverse electronic properties and ring systems were synthesized through multistep reactions. Preliminary structure-activity relationship (SAR) analysis revealed that compounds PTS-15 and PTS-22 significantly inhibited LPS-induced NO production in a concentration-dependent manner. Subsequent biological evaluation demonstrated that PTS-15 and PTS-22 inhibited the gene transcription of IL-1β, IL-6, and TNF-α. In addition, compound PTS-22 significantly inhibited the release of key pro-inflammatory cytokines, including IL-6 and TNF-α. Immunoblotting results further elucidated that PTS-22 exerts its anti-inflammatory efficacy by downregulating the NF-κB signaling pathway, as evidenced by the significant inhibition of p65 phosphorylation. Moreover, molecular docking analysis revealed the potential binding modes of PTS-15 and PTS-22 towards NF-κB. Collectively, these results highlighted the anti-inflammatory potential of phenylthiophene sulfonamide derivatives and supported their further optimization as scaffolds for the development of novel anti-inflammatory therapeutics.
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