Novel pyrimidine-1,3,4-oxadiazole hybrids and their precursors as potential antimycobacterial agents
Identifikátory výsledku
Kód výsledku v IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11160%2F23%3A10472136" target="_blank" >RIV/00216208:11160/23:10472136 - isvavai.cz</a>
Nalezeny alternativní kódy
RIV/71009396:_____/23:N0000037
Výsledek na webu
<a href="https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=pBUR7q62O8" target="_blank" >https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=pBUR7q62O8</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.4155/fmc-2023-0096" target="_blank" >10.4155/fmc-2023-0096</a>
Alternativní jazyky
Jazyk výsledku
angličtina
Název v původním jazyce
Novel pyrimidine-1,3,4-oxadiazole hybrids and their precursors as potential antimycobacterial agents
Popis výsledku v původním jazyce
Background: Molecular hybridization and isostery are proven approaches in medicinal chemistry, and as such we used them to design novel compounds that we investigated as potential antimycobacterials to combat drug-resistant strains. Methods & results: Prepared N-alkyl-2-(pyrimidine-5-carbonyl)hydrazine-1-carboxamides were cyclized to N-alkyl-5-(pyrimidin-5-yl)-1,3,4-oxadiazol-2-amines along with their analogues. A total of 48 compounds were tested against Mycobacterium tuberculosis H(37)Rv, Mycobacterium avium and Mycobacterium kansasii, with oxadiazoles and C(8)-C(12) alkyls being the most effective from a concentration of 2 mu M. Multidrug-resistant strains were inhibited at same concentrations as the susceptible strain. For the most potent N-dodecyl-5-(pyrimidin-5-yl)-1,3,4-oxadiazol-2-amine, the mechanism of action related to cell wall biosynthesis was investigated. Conclusion: Pyrimidine-1,3,4-oxadiazole hybrids are unique antimycobacterial agents inhibiting mainly M. tuberculosis strains without cross-resistance to current drugs and are thus promising drug candidates.
Název v anglickém jazyce
Novel pyrimidine-1,3,4-oxadiazole hybrids and their precursors as potential antimycobacterial agents
Popis výsledku anglicky
Background: Molecular hybridization and isostery are proven approaches in medicinal chemistry, and as such we used them to design novel compounds that we investigated as potential antimycobacterials to combat drug-resistant strains. Methods & results: Prepared N-alkyl-2-(pyrimidine-5-carbonyl)hydrazine-1-carboxamides were cyclized to N-alkyl-5-(pyrimidin-5-yl)-1,3,4-oxadiazol-2-amines along with their analogues. A total of 48 compounds were tested against Mycobacterium tuberculosis H(37)Rv, Mycobacterium avium and Mycobacterium kansasii, with oxadiazoles and C(8)-C(12) alkyls being the most effective from a concentration of 2 mu M. Multidrug-resistant strains were inhibited at same concentrations as the susceptible strain. For the most potent N-dodecyl-5-(pyrimidin-5-yl)-1,3,4-oxadiazol-2-amine, the mechanism of action related to cell wall biosynthesis was investigated. Conclusion: Pyrimidine-1,3,4-oxadiazole hybrids are unique antimycobacterial agents inhibiting mainly M. tuberculosis strains without cross-resistance to current drugs and are thus promising drug candidates.
Klasifikace
Druh
J<sub>imp</sub> - Článek v periodiku v databázi Web of Science
CEP obor
—
OECD FORD obor
30104 - Pharmacology and pharmacy
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
2023
Kód důvěrnosti údajů
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Údaje specifické pro druh výsledku
Název periodika
Future Medicinal Chemistry
ISSN
1756-8919
e-ISSN
1756-8927
Svazek periodika
15
Číslo periodika v rámci svazku
12
Stát vydavatele periodika
GB - Spojené království Velké Británie a Severního Irska
Počet stran výsledku
19
Strana od-do
1049-1067
Kód UT WoS článku
001043492000001
EID výsledku v databázi Scopus
2-s2.0-85169180507