Enhancing the antimycobacterial efficacy of pyridine-4-carbohydrazide: linkage to additional antimicrobial agents via oxocarboxylic acids
Identifikátory výsledku
Kód výsledku v IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F71009396%3A_____%2F25%3AN0000009" target="_blank" >RIV/71009396:_____/25:N0000009 - isvavai.cz</a>
Nalezeny alternativní kódy
RIV/00216208:11160/25:10486241
Výsledek na webu
<a href="https://pubs.rsc.org/en/content/articlelanding/2025/md/d4md00663a" target="_blank" >https://pubs.rsc.org/en/content/articlelanding/2025/md/d4md00663a</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1039/d4md00663a" target="_blank" >10.1039/d4md00663a</a>
Alternativní jazyky
Jazyk výsledku
angličtina
Název v původním jazyce
Enhancing the antimycobacterial efficacy of pyridine-4-carbohydrazide: linkage to additional antimicrobial agents via oxocarboxylic acids
Popis výsledku v původním jazyce
This study evaluates the antimycobacterial potential of novel "mutual" bioactive amides, combining pyridine-4-carbohydrazide (isoniazid, INH) with various antimicrobial agents (sulphonamides, 4-aminosalicylic acid, thiosemicarbazide, diphenyl (thio)ethers) via oxocarboxylic acids. The aim was to enhance activity against both drug-susceptible and multidrug-resistant (MDR) Mycobacterium tuberculosis and non-tuberculous strains, while overcoming drug resistance through dual-action mechanisms. Many derivatives exhibited potent antimycobacterial activity, with minimum inhibitory concentrations (MICs) as low as <= 0.25 mu M, outperforming INH, especially diphenyl (thio)ethers and biphenyl analogues. Additionally, the compounds were effective against M. kansasii (MICs <= 1 mu M) and inhibited MDR strains at higher concentrations (>= 8 mu M). The cytotoxicity assay indicated a favourable safety profile, with no significant haemolysis at 125 mu M, and some compounds were even protective. Selectivity for mycobacteria was confirmed by low inhibition of Gram-positive bacteria and inactivity against Gram-negative bacteria or fungi, highlighting the potential for further development as antimycobacterial agents.
Název v anglickém jazyce
Enhancing the antimycobacterial efficacy of pyridine-4-carbohydrazide: linkage to additional antimicrobial agents via oxocarboxylic acids
Popis výsledku anglicky
This study evaluates the antimycobacterial potential of novel "mutual" bioactive amides, combining pyridine-4-carbohydrazide (isoniazid, INH) with various antimicrobial agents (sulphonamides, 4-aminosalicylic acid, thiosemicarbazide, diphenyl (thio)ethers) via oxocarboxylic acids. The aim was to enhance activity against both drug-susceptible and multidrug-resistant (MDR) Mycobacterium tuberculosis and non-tuberculous strains, while overcoming drug resistance through dual-action mechanisms. Many derivatives exhibited potent antimycobacterial activity, with minimum inhibitory concentrations (MICs) as low as <= 0.25 mu M, outperforming INH, especially diphenyl (thio)ethers and biphenyl analogues. Additionally, the compounds were effective against M. kansasii (MICs <= 1 mu M) and inhibited MDR strains at higher concentrations (>= 8 mu M). The cytotoxicity assay indicated a favourable safety profile, with no significant haemolysis at 125 mu M, and some compounds were even protective. Selectivity for mycobacteria was confirmed by low inhibition of Gram-positive bacteria and inactivity against Gram-negative bacteria or fungi, highlighting the potential for further development as antimycobacterial agents.
Klasifikace
Druh
J<sub>imp</sub> - Článek v periodiku v databázi Web of Science
CEP obor
—
OECD FORD obor
10608 - Biochemistry and molecular biology
Návaznosti výsledku
Projekt
Výsledek vznikl pri realizaci vícero projektů. Více informací v záložce Projekty.
Návaznosti
P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)
Ostatní
Rok uplatnění
2025
Kód důvěrnosti údajů
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Údaje specifické pro druh výsledku
Název periodika
RSC Medicinal Chemistry
ISSN
2632-8682
e-ISSN
2632-8682
Svazek periodika
16
Číslo periodika v rámci svazku
2
Stát vydavatele periodika
GB - Spojené království Velké Británie a Severního Irska
Počet stran výsledku
12
Strana od-do
767-778
Kód UT WoS článku
001347638300001
EID výsledku v databázi Scopus
2-s2.0-85208781072