Evidence mapPaperPMID 39681576Full record

ArticleScientific reports2024

Re-design and evaluation of diclofenac-based carborane-substituted prodrugs and their anti-cancer potential.

Christoph Selg, Vuk Gordić, Tamara Krajnović, Antonio Buzharevski, Markus Laube, Aleksandr Kazimir, Peter Lönnecke, Mara Wolniewicz, Menyhárt B Sárosi, Jonas Schädlich 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 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing 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

7 citing papers in PubMed.

  1. Review
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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.

Christoph SelgDepartment of Chemistry and Mineralogy, Institute of Bioanalytical Chemistry, Leipzig University, Deutscher Platz 5, 04103, Leipzig, Germany.
Vuk GordićDepartment of Immunology, Institute for Biological Research "Siniša Stanković" - National Institute of the Republic of Serbia, University of Belgrade, Bulevar despota Stefana 142, Belgrade, 11108, Serbia.
Tamara KrajnovićDepartment of Immunology, Institute for Biological Research "Siniša Stanković" - National Institute of the Republic of Serbia, University of Belgrade, Bulevar despota Stefana 142, Belgrade, 11108, Serbia.
Antonio BuzharevskiDepartment of Chemistry and Mineralogy, Institute of Inorganic Chemistry, Leipzig University, Johannisallee 29, 04103, Leipzig, Germany.
Markus LaubeDepartment of Radiopharmaceutical and Chemical Biology, Institute of Radiopharmaceutical Cancer Research, Helmholtz-Zentrum Dresden-Rossendorf, Bautzner Landstraße 400, 01328, Dresden, Germany.
Aleksandr KazimirInstitute for Drug Discovery, Leipzig University, Brüderstraße 34, 04103, Leipzig, Germany.
Peter LönneckeDepartment of Chemistry and Mineralogy, Institute of Bioanalytical Chemistry, Leipzig University, Deutscher Platz 5, 04103, Leipzig, Germany.
Mara WolniewiczDepartment of Chemistry and Mineralogy, Institute of Organic Chemistry, Leipzig University, Johannisallee 29, 04103, Leipzig, Germany.
Menyhárt B SárosiDepartment of Chemistry and Mineralogy, Institute of Inorganic Chemistry, Leipzig University, Johannisallee 29, 04103, Leipzig, Germany.
Jonas SchädlichDepartment of Radiopharmaceutical and Chemical Biology, Institute of Radiopharmaceutical Cancer Research, Helmholtz-Zentrum Dresden-Rossendorf, Bautzner Landstraße 400, 01328, Dresden, Germany.
Jens PietzschDepartment of Radiopharmaceutical and Chemical Biology, Institute of Radiopharmaceutical Cancer Research, Helmholtz-Zentrum Dresden-Rossendorf, Bautzner Landstraße 400, 01328, Dresden, Germany.
Sanja MijatovićDepartment of Immunology, Institute for Biological Research "Siniša Stanković" - National Institute of the Republic of Serbia, University of Belgrade, Bulevar despota Stefana 142, Belgrade, 11108, Serbia.
Danijela Maksimović-IvanićDepartment of Immunology, Institute for Biological Research "Siniša Stanković" - National Institute of the Republic of Serbia, University of Belgrade, Bulevar despota Stefana 142, Belgrade, 11108, Serbia.
Evamarie Hey-HawkinsDepartment of Chemistry and Mineralogy, Institute of Bioanalytical Chemistry, Leipzig University, Deutscher Platz 5, 04103, Leipzig, Germany. hey@uni-leipzig.de.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

In this study, we investigated a novel anti-cancer drug design approach by revisiting diclofenac-based carborane-substituted prodrugs. The redesigned compounds combine the robust carborane scaffold with the oxindole framework, resulting in four carborane-derivatized oxindoles and a unique zwitterionic amidine featuring a nido-cluster. We tested the anti-cancer potential of these prodrugs against murine colon adenocarcinoma (MC38), human colorectal carcinoma (HCT116), and human colorectal adenocarcinoma (HT29). The tests showed that diclofenac and the carborane-substituted oxindoles exhibited no cytotoxicity, the dichlorophenyl-substituted oxindole had moderate anti-cancer activity, while with the amidine this effect was strongly potentiated with activity mapping within low micromolar range. Compound 3 abolished the viability of selected colon cancer cell line MC38 preferentially through strong inhibition of cell division and moderate apoptosis accompanied by ROS/RNS depletion. Our findings suggest that carborane-based prodrugs could be a promising direction for new anti-cancer therapies. Inhibition assays for COX-1 and COX-2 revealed that while diclofenac had strong COX inhibition, the re-engineered carborane compounds demonstrated a varied range of anti-cancer effects, probably owing to both, COX inhibition and COX-independent pathways.

Indexed as

Antineoplastic AgentsDiclofenacProdrugsAnimalsApoptosisBoranesCell Line, TumorCell ProliferationCell SurvivalColonic NeoplasmsCyclooxygenase 1Cyclooxygenase 2Cyclooxygenase InhibitorsDrug DesignHCT116 CellsHT29 CellsAntineoplastic AgentsBoranesCyclooxygenase 1Cyclooxygenase 2Cyclooxygenase InhibitorsDiclofenacProdrugsReactive Oxygen SpeciesCancerCarboranesCyclooxygenase inhibitorsDrug repurposingNon-steroidal anti-inflammatory drug

Identifiers

PMID39681576
PMCPMC11649784

What Socratic holds

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Registered trials

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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 Socratic graph.