Development of 3,5-dinitrobenzylsulfanyl-1,3,4-oxadiazoles and thiadiazoles as selective antitubercular agents active against replicating and nonreplicating Mycobacterium tuberculosis

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F60162694%3AG44__%2F16%3A43875575" target="_blank" >RIV/60162694:G44__/16:43875575 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/00216208:11160/16:10328675 RIV/71009396:_____/16:N0000010

Výsledek na webu

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

Jazyk výsledku

angličtina

Název v původním jazyce

Development of 3,5-dinitrobenzylsulfanyl-1,3,4-oxadiazoles and thiadiazoles as selective antitubercular agents active against replicating and nonreplicating Mycobacterium tuberculosis

Popis výsledku v původním jazyce

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.

Název v anglickém jazyce

Development of 3,5-dinitrobenzylsulfanyl-1,3,4-oxadiazoles and thiadiazoles as selective antitubercular agents active against replicating and nonreplicating Mycobacterium tuberculosis

Popis výsledku anglicky

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.

Druh

J_x - Nezařazeno - Článek v odborném periodiku (Jimp, Jsc a Jost)

CEP obor

FR - Farmakologie a lékárnická chemie

OECD FORD obor

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Projekt

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

Návaznosti

V - Vyzkumna aktivita podporovana z jinych verejnych zdroju

Rok uplatnění

2016

Kód důvěrnosti údajů

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

Název periodika

Journal of Medicinal Chemistry

ISSN

0022-2623

e-ISSN

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Svazek periodika

59

Číslo periodika v rámci svazku

6

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

19

Strana od-do

2362-2380

Kód UT WoS článku

000372946500007

EID výsledku v databázi Scopus

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