Antimicrobial and ADME properties of methoxylated, methylated
and nitrated 2-hydroxynaphthalene-1 carboxanilides

J 2025

Antimicrobial and ADME properties of methoxylated, methylated and nitrated 2-hydroxynaphthalene-1 carboxanilides

VRABLOVA, Lucia; Tomáš GONĚC; Tereza KAUEROVÁ; Michal ORAVEC; Izabela JENDRZEJEWSKA et. al.

Základní údaje

Originální název

Antimicrobial and ADME properties of methoxylated, methylated and nitrated 2-hydroxynaphthalene-1 carboxanilides

Autoři

VRABLOVA, Lucia; Tomáš GONĚC; Tereza KAUEROVÁ; Michal ORAVEC; Izabela JENDRZEJEWSKA; Peter KOLLÁR; Alois CIZEK 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

Organizační jednotka

Farmaceutická fakulta

DOI

https://doi.org/10.5599/admet.2642

UT WoS

001422088100001

Klíčová slova anglicky

Lipophilicity; antibacterial activity; antimycobacterial activity; cytotoxicity

Štítky

rivok, ÚChL, ÚFTo

Příznaky

Mezinárodní význam, Recenzováno

Změněno: 20. 3. 2025 14:16, Ing. Richard Heger, Ph.D.

Anotace

V originále

Background and purpose: Many new compounds are being prepared to overcome the problem of increasing microbial resistance and the increasing number of infections. Experimental approach: This study includes a series of twenty-seven mono-, di- and trisubstituted 2-hydroxynaphthalene-1-carboxanilides designed as multitarget agents. The compounds are substituted with methoxy, methyl, and nitro groups, as well as additionally with chlorine, bromine, and trifluoromethyl at various positions. All the compounds were evaluated for antibacterial activities against Gram-positive and Gram-negative bacteria and mycobacteria. Cytotoxicity on human cells was also tested. Key results: Three compounds showed activity comparable to clinically used drugs. N-(3,5-Dimethylphenyl)-2-hydroxynaphthalene-1-carboxamide (13) showed only antistaphylococcal activity (minimum inhibitory concentration (MIC) = 54.9 mu M); 2-hydroxy-N-[2-methyl-5-(trifluoro- methyl)phenyl]naphthalene-1-carboxamide (22) and 2-hydroxy-N-[4-nitro-3-(trifluoromethyl)phenyl]naphtha- lene-1-carboxamide (27) were active across the entire spectrum of tested bacteria/mycobacteria, both against the sensitive set and against resistant isolates (MICs range 0.3 to 92.6 mu M). Compound 22 was even active against E. coli (MIC = 23.2 mu M). The active agents showed no in vitro cytotoxicity up to a concentration of 30 mu M. Conclusion: Compounds with trifluoromethyl in the meta-anilide position, experimental lipophilicity expressed as log k (logarithm of the capacity factor) in the range of 0.31 to 0.34 and calculated electron sigma parameter for the anilide substituent higher than 0.59 were effective. The investigated compounds meet the definition of Michael acceptors. Based on ADME screening, the investigated compounds 13, 22 and 27 should have suitable physicochemical parameters for good bioavailability in the organism. Therefore, these are promising agents for further study. (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; Tereza KAUEROVÁ; Michal ORAVEC; Izabela JENDRZEJEWSKA; Peter KOLLÁR; Alois CIZEK a Josef JAMPILEK. Antimicrobial and ADME properties of methoxylated, methylated and nitrated 2-hydroxynaphthalene-1 carboxanilides. ADMET AND DMPK. CROATIA: IAPC PUBLISHING, 2025, roč. 13, č. 1, s. 1-21. ISSN 1848-7718. Dostupné z: https://doi.org/10.5599/admet.2642.

@article{2485503,
   author = {Vrablova, Lucia and Goněc, Tomáš and Kauerová, Tereza and Oravec, Michal and Jendrzejewska, Izabela and Kollár, Peter and Cizek, Alois and Jampilek, Josef},
   article_location = {CROATIA},
   article_number = {1},
   doi = {https://doi.org/10.5599/admet.2642},
   keywords = {Lipophilicity; antibacterial activity; antimycobacterial activity; cytotoxicity},
   language = {eng},
   issn = {1848-7718},
   journal = {ADMET AND DMPK},
   title = {Antimicrobial and ADME properties of methoxylated, methylated and nitrated 2-hydroxynaphthalene-1 carboxanilides},
   url = {https://pub.iapchem.org/ojs/index.php/admet/article/view/2642},
   volume = {13},
   year = {2025}
}

TY  - JOUR
ID  - 2485503
AU  - Vrablova, Lucia - Goněc, Tomáš - Kauerová, Tereza - Oravec, Michal - Jendrzejewska, Izabela - Kollár, Peter - Cizek, Alois - Jampilek, Josef
PY  - 2025
TI  - Antimicrobial and ADME properties of methoxylated, methylated and nitrated 2-hydroxynaphthalene-1 carboxanilides
JF  - ADMET AND DMPK
VL  - 13
IS  - 1
SP  - 1-21
EP  - 1-21
PB  - IAPC PUBLISHING
SN  - 18487718
KW  - Lipophilicity
KW  - antibacterial activity
KW  - antimycobacterial activity
KW  - cytotoxicity
UR  - https://pub.iapchem.org/ojs/index.php/admet/article/view/2642
N2  - Background and purpose: Many new compounds are being prepared to overcome the problem of increasing microbial resistance and the increasing number of infections. Experimental approach: This study includes a series of twenty-seven mono-, di- and trisubstituted 2-hydroxynaphthalene-1-carboxanilides designed as multitarget agents. The compounds are substituted with methoxy, methyl, and nitro groups, as well as additionally with chlorine, bromine, and trifluoromethyl at various positions. All the compounds were evaluated for antibacterial activities against Gram-positive and Gram-negative bacteria and mycobacteria. Cytotoxicity on human cells was also tested. Key results: Three compounds showed activity comparable to clinically used drugs. N-(3,5-Dimethylphenyl)-2-hydroxynaphthalene-1-carboxamide (13) showed only antistaphylococcal activity (minimum inhibitory concentration (MIC) = 54.9 mu M); 2-hydroxy-N-[2-methyl-5-(trifluoro- methyl)phenyl]naphthalene-1-carboxamide (22) and 2-hydroxy-N-[4-nitro-3-(trifluoromethyl)phenyl]naphtha- lene-1-carboxamide (27) were active across the entire spectrum of tested bacteria/mycobacteria, both against the sensitive set and against resistant isolates (MICs range 0.3 to 92.6 mu M). Compound 22 was even active against E. coli (MIC = 23.2 mu M). The active agents showed no in vitro cytotoxicity up to a concentration of 30 mu M. Conclusion: Compounds with trifluoromethyl in the meta-anilide position, experimental lipophilicity expressed as log k (logarithm of the capacity factor) in the range of 0.31 to 0.34 and calculated electron sigma parameter for the anilide substituent higher than 0.59 were effective. The investigated compounds meet the definition of Michael acceptors. Based on ADME screening, the investigated compounds 13, 22 and 27 should have suitable physicochemical parameters for good bioavailability in the organism. Therefore, these are promising agents for further study. (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; Tereza KAUEROVÁ; Michal ORAVEC; Izabela JENDRZEJEWSKA; Peter KOLLÁR; Alois CIZEK a Josef JAMPILEK. Antimicrobial and ADME properties of methoxylated, methylated and nitrated 2-hydroxynaphthalene-1 carboxanilides. \textit{ADMET AND DMPK}. CROATIA: IAPC PUBLISHING, 2025, roč.~13, č.~1, s.~1-21. ISSN~1848-7718. Dostupné z: https://doi.org/10.5599/admet.2642.

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