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

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F62157124%3A16170%2F25%3A43882574" target="_blank" >RIV/62157124:16170/25:43882574 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/00216224:14160/25:00140865 RIV/61989592:15310/25:73634948

Výsledek na webu

<a href="https://pmc.ncbi.nlm.nih.gov/articles/PMC11954145/" target="_blank" >https://pmc.ncbi.nlm.nih.gov/articles/PMC11954145/</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.5599/admet.2642" target="_blank" >10.5599/admet.2642</a>

Jazyk výsledku

angličtina

Název v původním jazyce

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

Popis výsledku v původním jazyce

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/).

Název v anglickém jazyce

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

Popis výsledku anglicky

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/).

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

40301 - Veterinary science

Projekt

—

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2025

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

ADMET &amp; DMPK

ISSN

1848-7718

e-ISSN

1848-7718

Svazek periodika

13

Číslo periodika v rámci svazku

1

Stát vydavatele periodika

HR - Chorvatská republika

Počet stran výsledku

21

Strana od-do

nestránkováno

Kód UT WoS článku

001422088100001

EID výsledku v databázi Scopus

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