Evidence map›Paper›PMID 38351313›Full record

ArticleScientific reports2024

Targeting yeast topoisomerase II by imidazo and triazoloacridinone derivatives resulting in their antifungal activity.

Kamila Rząd, Iwona Gabriel, Ewa Paluszkiewicz, Aleksandra Kuplińska, Mateusz Olszewski, Agnieszka Chylewska, Aleksandra M Dąbrowska, Katarzyna Kozłowska-Tylingo

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PubMed Full text at PMC Publisher
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 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
2.1field-weighted citation impact, top 14% of its field
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, 9 citations in OpenAlex.

  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

8 authors at 2 institutions in 1 country.

Kamila RządDepartment of Pharmaceutical Technology and Biochemistry, Faculty of Chemistry and BioTechMed Center, Gdansk University of Technology, 11/12 Narutowicza Str., 80-233, Gdansk, Poland. kamila.rzad@pg.edu.pl.
Iwona GabrielDepartment of Pharmaceutical Technology and Biochemistry, Faculty of Chemistry and BioTechMed Center, Gdansk University of Technology, 11/12 Narutowicza Str., 80-233, Gdansk, Poland.
Ewa PaluszkiewiczDepartment of Pharmaceutical Technology and Biochemistry, Faculty of Chemistry and BioTechMed Center, Gdansk University of Technology, 11/12 Narutowicza Str., 80-233, Gdansk, Poland.
Aleksandra KuplińskaDepartment of Pharmaceutical Technology and Biochemistry, Faculty of Chemistry and BioTechMed Center, Gdansk University of Technology, 11/12 Narutowicza Str., 80-233, Gdansk, Poland.
Mateusz OlszewskiDepartment of Pharmaceutical Technology and Biochemistry, Faculty of Chemistry and BioTechMed Center, Gdansk University of Technology, 11/12 Narutowicza Str., 80-233, Gdansk, Poland.
Agnieszka ChylewskaDepartment of Bioinorganic Chemistry, Faculty of Chemistry, University of Gdansk, Wita Stwosza 63, 80-308, Gdansk, Poland.
Aleksandra M DąbrowskaDepartment of Bioinorganic Chemistry, Faculty of Chemistry, University of Gdansk, Wita Stwosza 63, 80-308, Gdansk, Poland.
Katarzyna Kozłowska-TylingoDepartment of Pharmaceutical Technology and Biochemistry, Faculty of Chemistry and BioTechMed Center, Gdansk University of Technology, 11/12 Narutowicza Str., 80-233, Gdansk, Poland.
Gdańsk University of Technology · PLUniversity of Gdańsk · PL

Funding

Gdansk University of Technology, Poland DEC-24/2020/IDUB/I.3.3
6 · The paper itself

Abstract

Fungal pathogens are considered as serious factors for deadly diseases and are a case of medical concern. Invasive fungal infections also complicate the clinical course of COVID-19, leading to a significant increase in mortality. Furthermore, fungal strains' multidrug resistance has increased the demand for antifungals with a different mechanism of action. The present study aimed to identify antifungal compounds targeting yeast topoisomerase II (yTOPOII) derived from well-known human topoisomerase II (hTOPOII) poisons C-1305 and C-1311. Two sets of derivatives: triazoloacridinones (IKE1-8) and imidazoacridinones (IKE9-14) were synthetized and evaluated with a specific emphasis on the molecular mechanism of action. Our results indicated that their effectiveness as enzyme inhibitors was not solely due to intercalation ability but also as a result of influence on catalytic activity by the formation of covalent complexes between plasmid DNA and yTOPOII. Lysine conjunction increased the strength of the compound's interaction with DNA and improved penetration into the fungal cells. Triazoloacridinone derivatives in contrast to starting compound C-1305 exhibited moderate antifungal activity and at least twice lower cytotoxicity. Importantly, compounds (IKE5-8) were not substrates for multidrug ABC transporters whereas a derivative conjugated with lysine (IKE7), showed the ability to overcome C. glabrata fluconazole-resistance (MIC 32-64 µg mL

Indexed as

Antifungal AgentsLysineATP-Binding Cassette TransportersCandida glabrataDNAFluconazoleHumansMicrobial Sensitivity TestsAntifungal AgentsATP-Binding Cassette TransportersDNAFluconazoleLysine

Identifiers

PMID38351313
PMCPMC10864382
OpenAlexW4391785831

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.