biostudies-literatureFacen EAssociazione Italiana per la Ricerca sul CancroMinistero dell'Università e della RicercaMinistero della SaluteFondazione PezcollerMinisterstvo Školství, Mládeže a TělovýchovyMinistero dell’Università e della RicercaH2020 Marie Skłodowska-Curie ActionsEuropean Regional Development Fund24501https://www.ebi.ac.uk/biostudies/studies/S-EPMC11489580biostudies-literatureUnknown14(1)The RNA binding protein Human Antigen R (HuR) has been identified as a main regulator of the innate immune response and its inhibition can lead to beneficial anti-inflammatory effects. To this aim, we previously synthesized a novel class of small molecules named Tanshinone Mimics (TMs) able to interfere with HuR-RNA binding, and that dampen the LPS-induced immune response. Herein, we present a novel series of TMs, encompassing thiophene 3/TM9 and 4/TM10, furan 5/TM11 and 6/TM12, pyrrole 7b/TM13, and pyrazole 8. The furan-containing 5(TM11) showed the greatest inhibitory effect of the series on HuR-RNA complex formation, as suggested by RNA Electromobility Shift Assay and Time-Resolved FRET. Molecular Dynamics Calculation of HuR - 5/TM11 interaction, quantum mechanics approaches and SurfaceScientific reportsNovel, soluble 3-heteroaryl-substituted tanshinone mimics attenuate the inflammatory response in murine macrophages.PMC11489580GR2019-12369266LM2023042. CZ.02.1.01/0.0/0.0/18_046/001597481328421548PNRR-MUR NextGenerationEU cod. CN00000041Lotti RProvenzani AFacen EPaladino DMarinelli LHouser JPietra VAssoni GSeneci PCarreira ABonomo IArosio DDonati GFava LLfalseNovel, soluble 3-heteroaryl-substituted tanshinone mimics attenuate the inflammatory response in murine macrophages.The RNA binding protein Human Antigen R (HuR) has been identified as a main regulator of the innate immune response and its inhibition can lead to beneficial anti-inflammatory effects. To this aim, we previously synthesized a novel class of small molecules named Tanshinone Mimics (TMs) able to interfere with HuR-RNA binding, and that dampen the LPS-induced immune response. Herein, we present a novel series of TMs, encompassing thiophene 3/TM9 and 4/TM10, furan 5/TM11 and 6/TM12, pyrrole 7b/TM13, and pyrazole 8. The furan-containing 5(TM11) showed the greatest inhibitory effect of the series on HuR-RNA complex formation, as suggested by RNA Electromobility Shift Assay and Time-Resolved FRET. Molecular Dynamics Calculation of HuR - 5/TM11 interaction, quantum mechanics approaches and Surface2024-01-01T00:00:00Z2024 Oct2026-06-01T06:37:21.851Z2025-04-04T22:47:54.308ZS-EPMC114895803942462110.1038/s41598-024-73309-8