Development of 3,5-Dinitrobenzylsulfanyl-1,3,4-oxadiazoles and Thiadiazoles as Selective Antitubercular Agents Active Against Replicating and Nonreplicating Mycobacterium tuberculosis

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F71009396%3A_____%2F16%3AN0000010" target="_blank" >RIV/71009396:_____/16:N0000010 - isvavai.cz</a>

Alternative codes found

RIV/00216208:11160/16:10328675 RIV/60162694:G44__/16:43875575

Result on the web

<a href="https://pubs.acs.org/doi/pdf/10.1021/acs.jmedchem.5b00608" target="_blank" >https://pubs.acs.org/doi/pdf/10.1021/acs.jmedchem.5b00608</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1021/acs.jmedchem.5b00608" target="_blank" >10.1021/acs.jmedchem.5b00608</a>

Result language

angličtina

Original language name

Development of 3,5-Dinitrobenzylsulfanyl-1,3,4-oxadiazoles and Thiadiazoles as Selective Antitubercular Agents Active Against Replicating and Nonreplicating Mycobacterium tuberculosis

Original language description

Herein, we report the discovery and structure activity relationships of 5-substituted-2-[(3,5-dinitrobenzyl)-sulfanyl]-1,3,4-oxadiazoles and 1,3,4-thiadiazoles as a new class of antituberculosis agents. The majority of these compounds exhibited outstanding in vitro activity against Mycobacterium tuberculosis CNCTC My 331/88 and six multidrug-resistant clinically isolated strains of M. tuberculosis, with minimum inhibitory concentration values as low as 0.03 mu M (0.011-0.026 mu g/mL). The investigated compounds had a highly selective antimycobacterial effect because they showed no activity against the other bacteria or fungi tested in this study. Furthermore, the investigated compounds exhibited low in vitro toxicities in four proliferating mammalian cell lines and in isolated primary human hepatocytes. Several in vitro genotoxicity assays indicated that the selected compounds have no mutagenic activity. The oxadiazole and thiadiazole derivatives with the most favorable activity/toxicity profiles also showed potency comparable to that of rifampicin against the nonreplicating streptomycin-starved M. tuberculosis 18b-Lux strain, and therefore, these derivatives, are of particular interest.

Czech name

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Czech description

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Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

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OECD FORD branch

30104 - Pharmacology and pharmacy

Project

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Continuities

V - Vyzkumna aktivita podporovana z jinych verejnych zdroju

Publication year

2016

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

Journal of Medicinal Chemistry

ISSN

0022-2623

e-ISSN

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Volume of the periodical

59

Issue of the periodical within the volume

6

Country of publishing house

US - UNITED STATES

Number of pages

19

Pages from-to

2362-2380

UT code for WoS article

000372946500007

EID of the result in the Scopus database

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