5-(3,5-Dinitrophenyl)-1,3,4-oxadiazol-2-amine derivatives, their precursors, and analogues: Synthesis and evaluation of novel highly potent antitubercular agent

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F44555601%3A13440%2F25%3A43899419" target="_blank" >RIV/44555601:13440/25:43899419 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/00216208:11160/25:10498430

Výsledek na webu

<a href="https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0324608" target="_blank" >https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0324608</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1371/journal.pone.0324608" target="_blank" >10.1371/journal.pone.0324608</a>

Jazyk výsledku

angličtina

Název v původním jazyce

5-(3,5-Dinitrophenyl)-1,3,4-oxadiazol-2-amine derivatives, their precursors, and analogues: Synthesis and evaluation of novel highly potent antitubercular agent

Popis výsledku v původním jazyce

Drug resistance is a growing problem for many pathogens, including mycobacteria. Small heterocyclic molecules are among the leading scaffolds for developing potential antimycobacterial agents. Therefore, based on the molecular hybridization approach, we have prepared an extensive series of N-substituted 5-(3,5-dinitrophenyl)-1,3,4-oxadiazol-2-amine derivatives. We also investigated their isosteres and acyclic synthetic precursors. The compounds were evaluated for their in vitro activity against Mycobacterium tuberculosis (Mtb) H37Rv, a panel of multidrug- and extensively drug-resistant Mtb isolates and two nontuberculous mycobacterial strains (NTM; M. avium and M. kansasii). The ability to inhibit mycobacterial growth was quantified using minimum inhibitory concentration (MIC) values. Many compounds achieved MIC values &lt;= 0.03 mu M for NTM and Mtb, regardless of their resistance profile. The highest activity was associated with oxadiazole and thiadiazole scaffolds with benzylamino or C5-C9 alkylamino substitution. The experimentally confirmed mechanism of action of these compounds consists of disruption of mycobacterial cell wall biosynthesis via inhibition of decaprenylphosphoryl-beta-D-ribose 2&apos;-epimerase (DprE1). In vitro toxicity evaluation was performed in a hepatocyte model (HepG2), while in vivo toxicity was evaluated using Danio rerio embryos. These findings identify a promising new chemotype with potent, broad-spectrum and selective antimycobacterial activity, including efficacy against resistant strains, and support its further development as a potential therapeutic candidate.

Název v anglickém jazyce

5-(3,5-Dinitrophenyl)-1,3,4-oxadiazol-2-amine derivatives, their precursors, and analogues: Synthesis and evaluation of novel highly potent antitubercular agent

Popis výsledku anglicky

Drug resistance is a growing problem for many pathogens, including mycobacteria. Small heterocyclic molecules are among the leading scaffolds for developing potential antimycobacterial agents. Therefore, based on the molecular hybridization approach, we have prepared an extensive series of N-substituted 5-(3,5-dinitrophenyl)-1,3,4-oxadiazol-2-amine derivatives. We also investigated their isosteres and acyclic synthetic precursors. The compounds were evaluated for their in vitro activity against Mycobacterium tuberculosis (Mtb) H37Rv, a panel of multidrug- and extensively drug-resistant Mtb isolates and two nontuberculous mycobacterial strains (NTM; M. avium and M. kansasii). The ability to inhibit mycobacterial growth was quantified using minimum inhibitory concentration (MIC) values. Many compounds achieved MIC values &lt;= 0.03 mu M for NTM and Mtb, regardless of their resistance profile. The highest activity was associated with oxadiazole and thiadiazole scaffolds with benzylamino or C5-C9 alkylamino substitution. The experimentally confirmed mechanism of action of these compounds consists of disruption of mycobacterial cell wall biosynthesis via inhibition of decaprenylphosphoryl-beta-D-ribose 2&apos;-epimerase (DprE1). In vitro toxicity evaluation was performed in a hepatocyte model (HepG2), while in vivo toxicity was evaluated using Danio rerio embryos. These findings identify a promising new chemotype with potent, broad-spectrum and selective antimycobacterial activity, including efficacy against resistant strains, and support its further development as a potential therapeutic candidate.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30107 - Medicinal chemistry

Projekt

Výsledek vznikl pri realizaci vícero projektů. Více informací v záložce Projekty.

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

PLOS ONE

ISSN

1932-6203

e-ISSN

—

Svazek periodika

20

Číslo periodika v rámci svazku

5

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

32

Strana od-do

1-32

Kód UT WoS článku

001499341800040

EID výsledku v databázi Scopus

2-s2.0-105006635619