Development of 3,5-Dinitrophenyl-Containing 1,2,4-Triazoles and Their Trifluoromethyl Analogues as Highly Efficient Antitubercular Agents Inhibiting Decaprenylphosphoryl-beta-D-ribofuranose 2 '-Oxidase
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F60162694%3AG44__%2F19%3A00537297" target="_blank" >RIV/60162694:G44__/19:00537297 - isvavai.cz</a>
Alternative codes found
RIV/00216208:11160/19:10398817 RIV/00179906:_____/19:10398817 RIV/71009396:_____/19:N0000015
Result on the web
<a href="https://pubs.acs.org/doi/abs/10.1021/acs.jmedchem.9b00912" target="_blank" >https://pubs.acs.org/doi/abs/10.1021/acs.jmedchem.9b00912</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1021/acs.jmedchem.9b00912" target="_blank" >10.1021/acs.jmedchem.9b00912</a>
Alternative languages
Result language
angličtina
Original language name
Development of 3,5-Dinitrophenyl-Containing 1,2,4-Triazoles and Their Trifluoromethyl Analogues as Highly Efficient Antitubercular Agents Inhibiting Decaprenylphosphoryl-beta-D-ribofuranose 2 '-Oxidase
Original language description
We report herein the discovery of 3,5-dinitrophenyl 1,2,4-triazoles with excellent and selective antimycobacterial activities against Mycobacterium tuberculosis strains, including clinically isolated multidrug-resistant strains. Thorough structure activity relationship studies of 3,5-dinitrophenyl-containing 1,2,4-triazoles and their trifluoromethyl analogues revealed the key role of the position of the 3,5-dinitrophenyl fragment in the antitubercular efficiency. Among the prepared compounds, the highest in vitro antimycobacterial activities against M. tuberculosis H(37)Rv and against seven clinically isolated multidrug-resistant strains of M. tuberculosis were found with S-substituted 4-alkyl-5-(3,5-dinitrophenyl)-4H-1,2,4-triazole-3-thiols and their 3-nitro-5-(trifluoromethyl)phenyl analogues. The minimum inhibitory concentrations of these compounds reached 0.03 mu M, which is superior to all the current first-line anti-tuberculosis drugs. Furthermore, almost all compounds with excellent antimycobacterial activities exhibited very low in vitro cytotoxicities against two proliferating mammalian cell lines. The docking study indicated that these compounds acted as the inhibitors of decaprenylphosphoryl-beta-D-ribofuranose 2'-oxidase enzyme, which was experimentally confirmed by two independent radiolabeling experiments.
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
<a href="/en/project/EF16_019%2F0000841" target="_blank" >EF16_019/0000841: Efficiency and safety improvement of current drugs and nutraceuticals: advanced methods - new challenges</a><br>
Continuities
I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace
Others
Publication year
2019
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Journal of Medicinal Chemistry
ISSN
0022-2623
e-ISSN
1520-4804
Volume of the periodical
62
Issue of the periodical within the volume
17
Country of publishing house
US - UNITED STATES
Number of pages
25
Pages from-to
8115-8139
UT code for WoS article
000486361200034
EID of the result in the Scopus database
2-s2.0-85072133252