Development of water-soluble 3,5-dinitrophenyl tetrazole and oxadiazole antitubercular agents

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11160%2F17%3A10364741" target="_blank" >RIV/00216208:11160/17:10364741 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/60162694:G33__/17:N0000005 RIV/71009396:_____/17:N0000007

Výsledek na webu

<a href="http://www.sciencedirect.com/science/article/pii/S0968089617311136" target="_blank" >http://www.sciencedirect.com/science/article/pii/S0968089617311136</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1016/j.bmc.2017.08.010" target="_blank" >10.1016/j.bmc.2017.08.010</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Development of water-soluble 3,5-dinitrophenyl tetrazole and oxadiazole antitubercular agents

Popis výsledku v původním jazyce

In this work, four series of tertiary amine-containing derivatives of 3,5-dinitrophenyl tetrazole and oxadiazole antitubercular agents were prepared, and their in vitro antimycobacterial effects were evaluated. We found that the studied compounds showed lipophilicity-dependent antimycobacterial activity. The N-benzylpiperazine derivatives, which had the highest lipophilicity among all of the series, showed the highest in vitro antimycobacterial activities against Mycobacterium tuberculosis CNCTC My 331/88 (H(37)Rv), comparable to those of the first-line drugs isoniazid and rifampicin. The presence of two tertiary amines in these N-benzylpiperazine derivatives enabled us to prepare water-soluble dihydrochloride salts, overcoming the serious drawback of previously described 3,5-dinitrophenyl tetrazole and oxadiazole lead compounds. The water-soluble 3,5-dinitrophenyl tetrazole and oxadiazole antitubercular agents described in this work are good candidates for further in vitro and in vivo pharmacokinetic and pharmacodynamic studies.

Název v anglickém jazyce

Development of water-soluble 3,5-dinitrophenyl tetrazole and oxadiazole antitubercular agents

Popis výsledku anglicky

In this work, four series of tertiary amine-containing derivatives of 3,5-dinitrophenyl tetrazole and oxadiazole antitubercular agents were prepared, and their in vitro antimycobacterial effects were evaluated. We found that the studied compounds showed lipophilicity-dependent antimycobacterial activity. The N-benzylpiperazine derivatives, which had the highest lipophilicity among all of the series, showed the highest in vitro antimycobacterial activities against Mycobacterium tuberculosis CNCTC My 331/88 (H(37)Rv), comparable to those of the first-line drugs isoniazid and rifampicin. The presence of two tertiary amines in these N-benzylpiperazine derivatives enabled us to prepare water-soluble dihydrochloride salts, overcoming the serious drawback of previously described 3,5-dinitrophenyl tetrazole and oxadiazole lead compounds. The water-soluble 3,5-dinitrophenyl tetrazole and oxadiazole antitubercular agents described in this work are good candidates for further in vitro and in vivo pharmacokinetic and pharmacodynamic studies.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30104 - Pharmacology and pharmacy

Projekt

—

Návaznosti

S - Specificky vyzkum na vysokych skolach<br>I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2017

Kód důvěrnosti údajů

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

Název periodika

Bioorganic &amp; Medicinal Chemistry

ISSN

0968-0896

e-ISSN

—

Svazek periodika

25

Číslo periodika v rámci svazku

20

Stát vydavatele periodika

GB - Spojené království Velké Británie a Severního Irska

Počet stran výsledku

9

Strana od-do

5468-5476

Kód UT WoS článku

000413402100028

EID výsledku v databázi Scopus

2-s2.0-85028022360