Design and biological evaluation of mesalamine-NSAID hybrids targeting the NLRP3 inflammasome: a multi-target strategy for ulcerative colitis therapy.

Misagh Yahya, Javad Safaei-Ghomi, Abdolrasoul Haghir-Ebrahimabadi, Hanieh Jalali, Hossein Mojtabazadeh

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Article in Scientific reports, 2025. 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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5 · Who and what money

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5 authors.

Misagh YahyaDepartment of Organic Chemistry, Faculty of Chemistry, University of Kashan, Kashan, Iran.

Javad Safaei-GhomiDepartment of Organic Chemistry, Faculty of Chemistry, University of Kashan, Kashan, Iran. safaei@kashanu.ac.ir.

Abdolrasoul Haghir-EbrahimabadiDepartment of Organic Chemistry, Faculty of Chemistry, University of Kashan, Kashan, Iran.

Hanieh JalaliDepartment of Animal Biology, Faculty of Biological Sciences, Kharazmi University, Tehran, Iran.

Hossein MojtabazadehDepartment of Organic Chemistry, Faculty of Chemistry, University of Kashan, Kashan, Iran.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Ulcerative colitis (UC) is a chronic inflammatory bowel disease characterized by epithelial damage, excessive cytokine release, and dysregulated inflammasome activation. Herein, we report the design, synthesis, and multi-targeted biological evaluation of three novel mesalamine-NSAID hybrid derivatives (D1, D3, and D4) as potential therapeutic agents for UC. Structural hybridization was employed to enhance colonic targeting, suppress NLRP3 inflammasome signaling, and reduce systemic toxicity. All compounds were characterized and screened for anti-inflammatory efficacy via qRT-PCR analysis of key inflammasome-related genes (NLRP3, IL1B, IL-18, Caspase-1) in LPS-activated macrophages. Compound D3 exhibited the most potent downregulation profile, supported by molecular docking studies showing favorable interactions with NLRP3 and caspase-1. Antioxidant activity was evaluated using the DPPH assay, with D3 demonstrating the lowest IC

Indexed as

Anti-Inflammatory Agents, Non-SteroidalColitis, UlcerativeInflammasomesMesalamineNLR Family, Pyrin Domain-Containing 3 ProteinAnimalsAntioxidantsDrug DesignHumansMacrophagesMiceMolecular Docking SimulationRAW 264.7 CellsAnti-Inflammatory Agents, Non-SteroidalAntioxidantsInflammasomesMesalamineNLR Family, Pyrin Domain-Containing 3 ProteinAnti-inflammatory agentsAntioxidant activityMesalamine–NSAID hybridsMolecular dockingNLRP3 inflammasomeqRT-PCRUlcerative colitis

Identifiers

PMID41388071

DOI10.1038/s41598-025-31910-5

PMCPMC12808315

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.