5-(3,5-Dinitrophenyl)-1,3,4-oxadiazol-2-amine derivatives, their precursors, and analogues: Synthesis and evaluation of novel highly potent antitubercular agent
The result's identifiers
Result code in 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>
Alternative codes found
RIV/00216208:11160/25:10498430
Result on the web
<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>
Alternative languages
Result language
angličtina
Original language name
5-(3,5-Dinitrophenyl)-1,3,4-oxadiazol-2-amine derivatives, their precursors, and analogues: Synthesis and evaluation of novel highly potent antitubercular agent
Original language description
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 <= 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'-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.
Czech name
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Czech description
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Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
30107 - Medicinal chemistry
Result continuities
Project
Result was created during the realization of more than one project. More information in the Projects tab.
Continuities
I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace
Others
Publication year
2025
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
PLOS ONE
ISSN
1932-6203
e-ISSN
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Volume of the periodical
20
Issue of the periodical within the volume
5
Country of publishing house
US - UNITED STATES
Number of pages
32
Pages from-to
1-32
UT code for WoS article
001499341800040
EID of the result in the Scopus database
2-s2.0-105006635619