Evidence map›Paper›PMID 41251215›Full record

ArticleChemMedChem2025

Design, Synthesis, and Biological Characterization of Macromolecular Ester Prodrugs of a Selective Cyclooxygenase-2 Inhibitor.

Mario Saletti, Marco Paolino, Jacopo Venditti, Germano Giuliani, Antonietta Rossi, Danilo D'Avino, Sara Perna, Ina Varfaj, Roccaldo Sardella, Antonio Macchiarulo and 4 more

Abstract read
In one paragraph

Article in ChemMedChem, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing 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

2 citing papers in PubMed.

  1. Article
  2. 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.

Mario SalettiDipartimento di Biotecnologie, Chimica e Farmacia, Università degli Studi di Siena, Via Aldo Moro 2, 53100, Siena, Italy.
Marco PaolinoDipartimento di Biotecnologie, Chimica e Farmacia, Università degli Studi di Siena, Via Aldo Moro 2, 53100, Siena, Italy.ORCID https://orcid.org/0000-0003-1387-7875
Jacopo VendittiDipartimento di Biotecnologie, Chimica e Farmacia, Università degli Studi di Siena, Via Aldo Moro 2, 53100, Siena, Italy.ORCID https://orcid.org/0009-0003-3811-744X
Germano GiulianiDipartimento di Biotecnologie, Chimica e Farmacia, Università degli Studi di Siena, Via Aldo Moro 2, 53100, Siena, Italy.ORCID https://orcid.org/0000-0001-8111-3776
Antonietta RossiDipartimento di Farmacia, Scuola di Medicina e Chirurgia, Università di Napoli "Federico II", Via D. Montesano 49, I-80131, Napoli, Italy.ORCID https://orcid.org/0000-0002-3237-2584
Danilo D'AvinoDipartimento di Farmacia, Scuola di Medicina e Chirurgia, Università di Napoli "Federico II", Via D. Montesano 49, I-80131, Napoli, Italy.ORCID https://orcid.org/0000-0002-6350-5191
Sara PernaDipartimento di Farmacia, Scuola di Medicina e Chirurgia, Università di Napoli "Federico II", Via D. Montesano 49, I-80131, Napoli, Italy.
Ina VarfajDipartimento di Scienze Farmaceutiche, Università di Perugia, Via Fabretti 48, 06123, Perugia, Italy.ORCID https://orcid.org/0000-0003-4905-7115
Roccaldo SardellaDipartimento di Scienze Farmaceutiche, Università di Perugia, Via Fabretti 48, 06123, Perugia, Italy.ORCID https://orcid.org/0000-0001-9856-0230
Antonio MacchiaruloDipartimento di Scienze Farmaceutiche, Università di Perugia, Via Fabretti 48, 06123, Perugia, Italy.ORCID https://orcid.org/0000-0001-9535-4183
Samuele MaramaiDipartimento di Biotecnologie, Chimica e Farmacia, Università degli Studi di Siena, Via Aldo Moro 2, 53100, Siena, Italy.ORCID https://orcid.org/0000-0001-7499-6961
Stefania LamponiDipartimento di Biotecnologie, Chimica e Farmacia, Università degli Studi di Siena, Via Aldo Moro 2, 53100, Siena, Italy.
Andrea CappelliDipartimento di Biotecnologie, Chimica e Farmacia, Università degli Studi di Siena, Via Aldo Moro 2, 53100, Siena, Italy.ORCID https://orcid.org/0000-0003-4140-3028
Maurizio AnziniDipartimento di Biotecnologie, Chimica e Farmacia, Università degli Studi di Siena, Via Aldo Moro 2, 53100, Siena, Italy.ORCID https://orcid.org/0000-0002-7481-5566

Funding

European Union-Next Generation EU under the Italian Ministry of University and Research (MUR) National Innovation Ecosystem ECS00000041 - VITALITY - CUP J97G22000170005Italian Ministry of University and Research PRIN 2022 PNRRUniversity of Naples Federico II - Department of Pharmacy, "Progetto di Eccellenza 2022-2027" TRAVEL
6 · The paper itself

Abstract

Owing to the importance of tracing new routes in the development of macromolecular prodrugs, in the present work, two potential macromolecular ester prodrugs (i.e., 12a and 13a) of selective cyclooxygenase-2 (COX-2) inhibitor 7b are designed and synthesized. In the design, two different oligo(ethylene glycol)-based spacers are linked through a ferulate residue to the backbone hyaluronic acid (HA) showing a medium molar mass value (i.e., Mw = 270 kDa). The spacers are designed to differ in the sensitivity to the hydrolytic conditions so that the chemical hydrolysis of ferulate ester bond in 12a is assumed to produce the corresponding ferulic acid derivative 12b. On the other hand, the same reaction in 13a leading to ferulate derivative 13b could be accompanied by the hydrolysis of the second ester bond with the release of the selective COX-2 inhibitor 7b. The COX inhibitory activity of the newly synthesized compounds is evaluated in vitro, and macromolecular ester prodrugs 12a and 13a are found to be completely inactive together with hydrolysis product 12b. Conversely, these in vitro studies reveal the intriguing COX-2 inhibitory activity and selectivity of ferulate derivative 13b related to macromolecular ester prodrug 13a. Therefore, to obtain information on the hydrolysis process in different environments, hydrolysis studies are performed on macromolecular ester prodrug 13a by using

Indexed as

Cyclooxygenase 2Cyclooxygenase 2 InhibitorsDrug DesignEstersProdrugsCoumaric AcidsHumansHydrolysisMacromolecular SubstancesMolecular StructureStructure-Activity RelationshipCoumaric AcidsCyclooxygenase 2Cyclooxygenase 2 InhibitorsEstersMacromolecular SubstancesProdrugsanti‐inflammatory agentsCOX‐2 inhibitorsferulic acidhyaluronic acidprodrugs

Identifiers

PMID41251215
PMCPMC12711161

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.