Insight into antistaphylococcal effect of chlorinated
1-hydroxynaphthalene-2-carboxanilides

J 2025

Insight into antistaphylococcal effect of chlorinated 1-hydroxynaphthalene-2-carboxanilides

VRABLOVA, Lucia; Tomáš GONĚC; Petra MAJEROVA; Andrej KOVAC; Dominika KOS et al.

Základní údaje

Originální název

Insight into antistaphylococcal effect of chlorinated 1-hydroxynaphthalene-2-carboxanilides

Autoři

VRABLOVA, Lucia; Tomáš GONĚC ; Petra MAJEROVA; Andrej KOVAC; Dominika KOS ; Peter KOLLÁR ; Jiří KOS; Alois CIZEK; Tereza KAUEROVÁ a Josef JAMPILEK

Vydání

ADMET AND DMPK, CROATIA, IAPC PUBLISHING, 2025, 1848-7718

Další údaje

Jazyk

angličtina

Typ výsledku

Článek v odborném periodiku

Obor

30107 Medicinal chemistry

Stát vydavatele

Chorvatsko

Utajení

není předmětem státního či obchodního tajemství

Odkazy

URL

Impakt faktor

Impact factor: 4.300 v roce 2024

Označené pro přenos do RIV

Ano

Kód RIV

RIV/00216224:14160/25:00141034

Organizační jednotka

Farmaceutická fakulta

Klíčová slova anglicky

Lipophilicity; antistaphylococcal activity; cytotoxicity; MTT assay; chemoproteomic analysis

Štítky

14110512, podil, rivok, ÚChL, ÚFTo, ÚMF

Příznaky

Mezinárodní význam, Recenzováno

Změněno: 8. 4. 2026 09:26, Mgr. Irena Doubková

Anotace

V originále

Background and purpose: New compounds and innovative therapeutic approaches are trying to prevent antimicrobial resistance, which has become a global health challenge. Experimental approach: This study includes a series of twelve mono-, di- and trichlorinated 1-hydroxynaphthalene-2-carboxanilides designed as multitarget agents. All compounds were evaluated for their antistaphylococcal activity. Furthermore, MTT assay and chemoproteomic analysis of selected compounds were performed. Cytotoxicity in human cells was also tested. Key results: N-(3,5-Dichlorophenyl)-1-hydroxynaphthalene-2-carboxamide (10) demonstrated activity comparable to or higher than clinically used drugs, with minimum inhibitory concentrations (MICs) of 0.37 p.M. The compound was equally effective against clinical isolates of methicillin-resistant S. aureus. On the other hand, compound 10 showed 96 % inhibition of S. aureus respiration only at a concentration of 16x MIC. Chemoproteomic analysis revealed that the effect of agent 10 on staphylococci resulted in the downregulation of four proteins. This compound expressed no in vitro cytotoxicity up to a concentration of 30 p.M. Conclusion: From the set of tested mono-, di- and trisubstituted derivatives, it is evident that the position of chlorine atoms is decisive for significant antistaphylococcal activity. Inhibition of energy metabolism does not appear to be one of the main mechanisms of action of compound 10; on the contrary, the antibacterial effect may likely be contributed by downregulation of proteins (especially ATPdependent protease ATPase subunit HslU) involved in processes essential for bacterial survival and growth, such as protein, nucleotide/nucleic acid synthesis and efficient protein repair/degradation. (c) 2025 by the authors. This article is an open-access article distributed under the terms and conditions of the Creative Commons Attribution license (http://creativecommons.org/licenses/by/4.0/).

Citovat

VRABLOVA, Lucia; Tomáš GONĚC; Petra MAJEROVA; Andrej KOVAC; Dominika KOS; Peter KOLLÁR; Jiří KOS; Alois CIZEK; Tereza KAUEROVÁ a Josef JAMPILEK. Insight into antistaphylococcal effect of chlorinated 1-hydroxynaphthalene-2-carboxanilides. ADMET AND DMPK. CROATIA: IAPC PUBLISHING, 2025, roč. 13, č. 2, s. 1-17. ISSN 1848-7718. Dostupné z: https://doi.org/10.5599/admet.2684.

@article{2492365,
   author = {Vrablova, Lucia and Goněc, Tomáš and Majerova, Petra and Kovac, Andrej and Kos, Dominika and Kollár, Peter and Kos, Jiří and Cizek, Alois and Kauerová, Tereza and Jampilek, Josef},
   article_location = {CROATIA},
   article_number = {2},
   doi = {https://doi.org/10.5599/admet.2684},
   keywords = {Lipophilicity; antistaphylococcal activity; cytotoxicity; MTT assay; chemoproteomic analysis},
   language = {eng},
   issn = {1848-7718},
   journal = {ADMET AND DMPK},
   title = {Insight into antistaphylococcal effect of chlorinated 1-hydroxynaphthalene-2-carboxanilides},
   url = {https://pub.iapchem.org/ojs/index.php/admet/article/view/2684},
   volume = {13},
   year = {2025}
}

TY  - JOUR
ID  - 2492365
AU  - Vrablova, Lucia - Goněc, Tomáš - Majerova, Petra - Kovac, Andrej - Kos, Dominika - Kollár, Peter - Kos, Jiří - Cizek, Alois - Kauerová, Tereza - Jampilek, Josef
PY  - 2025
TI  - Insight into antistaphylococcal effect of chlorinated 1-hydroxynaphthalene-2-carboxanilides
JF  - ADMET AND DMPK
VL  - 13
IS  - 2
SP  - 1-17
EP  - 1-17
PB  - IAPC PUBLISHING
SN  - 18487718
KW  - Lipophilicity
KW  - antistaphylococcal activity
KW  - cytotoxicity
KW  - MTT assay
KW  - chemoproteomic analysis
UR  - https://pub.iapchem.org/ojs/index.php/admet/article/view/2684
N2  - Background and purpose: New compounds and innovative therapeutic approaches are trying to prevent antimicrobial resistance, which has become a global health challenge. Experimental approach: This study includes a series of twelve mono-, di- and trichlorinated 1-hydroxynaphthalene-2-carboxanilides designed as multitarget agents. All compounds were evaluated for their antistaphylococcal activity. Furthermore, MTT assay and chemoproteomic analysis of selected compounds were performed. Cytotoxicity in human cells was also tested. Key results: N-(3,5-Dichlorophenyl)-1-hydroxynaphthalene-2-carboxamide (10) demonstrated activity comparable to or higher than clinically used drugs, with minimum inhibitory concentrations (MICs) of 0.37 p.M. The compound was equally effective against clinical isolates of methicillin-resistant S. aureus. On the other hand, compound 10 showed 96 % inhibition of S. aureus respiration only at a concentration of 16x MIC. Chemoproteomic analysis revealed that the effect of agent 10 on staphylococci resulted in the downregulation of four proteins. This compound expressed no in vitro cytotoxicity up to a concentration of 30 p.M. Conclusion: From the set of tested mono-, di- and trisubstituted derivatives, it is evident that the position of chlorine atoms is decisive for significant antistaphylococcal activity. Inhibition of energy metabolism does not appear to be one of the main mechanisms of action of compound 10; on the contrary, the antibacterial effect may likely be contributed by downregulation of proteins (especially ATPdependent protease ATPase subunit HslU) involved in processes essential for bacterial survival and growth, such as protein, nucleotide/nucleic acid synthesis and efficient protein repair/degradation. (c) 2025 by the authors. This article is an open-access article distributed under the terms and conditions of the Creative Commons Attribution license (http://creativecommons.org/licenses/by/4.0/).
ER  -

VRABLOVA, Lucia; Tomáš GONĚC; Petra MAJEROVA; Andrej KOVAC; Dominika KOS; Peter KOLLÁR; Jiří KOS; Alois CIZEK; Tereza KAUEROVÁ a Josef JAMPILEK. Insight into antistaphylococcal effect of chlorinated 1-hydroxynaphthalene-2-carboxanilides. \textit{ADMET AND DMPK}. CROATIA: IAPC PUBLISHING, 2025, roč.~13, č.~2, s.~1-17. ISSN~1848-7718. Dostupné z: https://doi.org/10.5599/admet.2684.

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