Structure-activity relationship studies on 3,5-dinitrophenyl tetrazoles as antitubercular agents

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11160%2F17%3A10364537" target="_blank" >RIV/00216208:11160/17:10364537 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/00179906:_____/17:10364537 RIV/71009396:_____/17:N0000025

Výsledek na webu

<a href="http://www.sciencedirect.com/science/article/pii/S0223523417301411" target="_blank" >http://www.sciencedirect.com/science/article/pii/S0223523417301411</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1016/j.ejmech.2017.02.058" target="_blank" >10.1016/j.ejmech.2017.02.058</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Structure-activity relationship studies on 3,5-dinitrophenyl tetrazoles as antitubercular agents

Popis výsledku v původním jazyce

In this study, we described the structure-activity relationships of substituted 3,5-dinitrophenyl tetrazoles as potent antitubercular agents. These simple and readily accessible compounds possessed high in vitro antimycobacterial activities against Mycobacterium tuberculosis, including clinically isolated multidrug (MDR) and extensively drug-resistant (XDR) strains, with submicromolar minimum inhibitory concentrations (MICs). The most promising compounds showed low in vitro cytotoxicity and negligible antibacterial and antifungal activities, highlighting their highly selective antimycobacterial effects. 2-Substituted 5-(3,5- dinitrophenyl)-2H-tetrazole regioisomers, which are the dominant products of 5(3,5- dinitrophenyl)-1H-tetrazole alkylation, showed better properties with respect to antimycobacterial activity and cytotoxicity than their 1-substituted counterparts. The 2-substituent of 5-(3,5dinitrophenyl)-2H-tetrazole can be easily modified and can thus be used for the structure optimization of these promising antitubercular agents. The introduction of a tetrazole-5-thioalkyl moiety at position 2 of the tetrazole further increased the antimycobacterial activity. These compounds showed outstanding in vitro activity against M. tuberculosis (MIC values as low as 0.03 mu M) and high activity against non-tuberculous mycobacterial strains.

Název v anglickém jazyce

Structure-activity relationship studies on 3,5-dinitrophenyl tetrazoles as antitubercular agents

Popis výsledku anglicky

In this study, we described the structure-activity relationships of substituted 3,5-dinitrophenyl tetrazoles as potent antitubercular agents. These simple and readily accessible compounds possessed high in vitro antimycobacterial activities against Mycobacterium tuberculosis, including clinically isolated multidrug (MDR) and extensively drug-resistant (XDR) strains, with submicromolar minimum inhibitory concentrations (MICs). The most promising compounds showed low in vitro cytotoxicity and negligible antibacterial and antifungal activities, highlighting their highly selective antimycobacterial effects. 2-Substituted 5-(3,5- dinitrophenyl)-2H-tetrazole regioisomers, which are the dominant products of 5(3,5- dinitrophenyl)-1H-tetrazole alkylation, showed better properties with respect to antimycobacterial activity and cytotoxicity than their 1-substituted counterparts. The 2-substituent of 5-(3,5dinitrophenyl)-2H-tetrazole can be easily modified and can thus be used for the structure optimization of these promising antitubercular agents. The introduction of a tetrazole-5-thioalkyl moiety at position 2 of the tetrazole further increased the antimycobacterial activity. These compounds showed outstanding in vitro activity against M. tuberculosis (MIC values as low as 0.03 mu M) and high activity against non-tuberculous mycobacterial strains.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30104 - Pharmacology and pharmacy

Projekt

<a href="/cs/project/GA14-08423S" target="_blank" >GA14-08423S: Studie vztahů struktura-aktivita-toxicita ve skupině nízkomolekulárních sloučenin s antimykobacterialní aktivitou</a><br>

Návaznosti

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Rok uplatnění

2017

Kód důvěrnosti údajů

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

Název periodika

European Journal of Medicinal Chemistry

ISSN

0223-5234

e-ISSN

—

Svazek periodika

130

Číslo periodika v rámci svazku

April

Stát vydavatele periodika

FR - Francouzská republika

Počet stran výsledku

14

Strana od-do

419-432

Kód UT WoS článku

000397180900032

EID výsledku v databázi Scopus

2-s2.0-85014464603