Evidence map›Paper›PMID 39424621›Full record

ArticleScientific reports2024

Novel, soluble 3-heteroaryl-substituted tanshinone mimics attenuate the inflammatory response in murine macrophages.

Elisa Facen, Giulia Assoni, Greta Donati, Dalila Paladino, Agata Carreira, Isabelle Bonomo, Valeria La Pietra, Roberta Lotti, Josef Houser, Luca L Fava and 4 more

Abstract read
In one paragraph

Article in Scientific reports, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

3 citing papers in PubMed.

  1. Article
  2. Synthesis and crystal structure of 5-{(Acta crystallographica. Section E, Crystallographic communications · 2025
    Article
  3. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

14 authors.

Elisa Facen *Department of Cellular, Computational and Integrative Biology (CIBIO), University of Trento, Via Sommarive 9, Trento, 38123, Italy.
Giulia Assoni *Department of Cellular, Computational and Integrative Biology (CIBIO), University of Trento, Via Sommarive 9, Trento, 38123, Italy.
Greta DonatiDepartment of Pharmacy, University of Napoli Federico II, Via D. Montesano 49, Napoli, 80131, Italy.
Dalila PaladinoDepartment of Cellular, Computational and Integrative Biology (CIBIO), University of Trento, Via Sommarive 9, Trento, 38123, Italy.
Agata CarreiraDepartment of Cellular, Computational and Integrative Biology (CIBIO), University of Trento, Via Sommarive 9, Trento, 38123, Italy.
Isabelle BonomoDepartment of Cellular, Computational and Integrative Biology (CIBIO), University of Trento, Via Sommarive 9, Trento, 38123, Italy.
Valeria La PietraDepartment of Pharmacy, University of Napoli Federico II, Via D. Montesano 49, Napoli, 80131, Italy.
Roberta LottiDERMOLAB, University of Modena and Reggio Emilia, via del Pozzo, 71, Modena, 41124, Italy.
Josef HouserCentral European Institute of Technology, Masaryk University, Kamenice 753/5, Brno, 625 00, Czech Republic.
Luca L FavaDepartment of Cellular, Computational and Integrative Biology (CIBIO), University of Trento, Via Sommarive 9, Trento, 38123, Italy.
Pierfausto SeneciDepartment of Chemistry, University of Milan, Via Golgi 19, Milan, 20133, Italy.
Luciana MarinelliDepartment of Pharmacy, University of Napoli Federico II, Via D. Montesano 49, Napoli, 80131, Italy. lmarinel@unina.it.
Daniela ArosioIstituto di Scienze e Tecnologie Chimiche (SCITEC) 'Giulio Natta', Consiglio Nazionale delle Ricerche (CNR), Via C. Golgi 19, Milan, 20133, Italy. daniela.arosio@scitec.cnr.it.
Alessandro ProvenzaniDepartment of Cellular, Computational and Integrative Biology (CIBIO), University of Trento, Via Sommarive 9, Trento, 38123, Italy. alessandro.provenzani@unitn.it.

Funding

Associazione Italiana per la Ricerca sul Cancro 21548European Regional Development Fund . CZ.02.1.01/0.0/0.0/18_046/0015974H2020 Marie Skłodowska-Curie Actions 813284Ministero della Salute GR2019-12369266Ministero dell'Università e della Ricerca PNRR-MUR NextGenerationEU cod. CN00000041Ministerstvo Školství, Mládeže a Tělovýchovy LM2023042
6 · The paper itself

Abstract

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 Surface Plasmon Resonance data, all indicates that, within the novel heteroaryl substituents, the furan ring better recapitulates the chemical features of the RNA bound to HuR. Compound 5/TM11 also showed improved aqueous solubility compared to previously reported TMs. Real-time monitoring of cell growth and flow cytometry analyses showed that 5/TM11 preferentially reduced cell proliferation rather than apoptosis in murine macrophages at immunomodulatory doses. We observed its effects on the innate immune response triggered by lipopolysaccharide (LPS) in macrophages, showing that 5/TM11 significantly reduced the expression of proinflammatory cytokines as Cxcl10 and Il1b.

Indexed as

AbietanesMacrophagesAnimalsAnti-Inflammatory AgentsApoptosisChemokine CXCL10ELAV-Like Protein 1FuransHumansInflammationLipopolysaccharidesMiceMolecular Dynamics SimulationRAW 264.7 CellsSolubilityAbietanesAnti-Inflammatory AgentsChemokine CXCL10ELAV-Like Protein 1FuransLipopolysaccharidestanshinoneAnti-inflammatory agentsELAVL1HuRHuR inhibitorsLPSTanshinone mimics

Identifiers

PMID39424621
PMCPMC11489580

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

None linked

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.