Discovery of new antitubercular agents by combining pyrazoline and benzoxazole pharmacophores: design, synthesis and insights into the binding interactions

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61388963%3A_____%2F14%3A00427728" target="_blank" >RIV/61388963:_____/14:00427728 - isvavai.cz</a>

Výsledek na webu

<a href="http://dx.doi.org/10.1007/s00044-013-0815-x" target="_blank" >http://dx.doi.org/10.1007/s00044-013-0815-x</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1007/s00044-013-0815-x" target="_blank" >10.1007/s00044-013-0815-x</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Discovery of new antitubercular agents by combining pyrazoline and benzoxazole pharmacophores: design, synthesis and insights into the binding interactions

Popis výsledku v původním jazyce

The present study is aimed at combining two well-known pharmacophores (pyrazoline and benzoxazole nucleus) to design and synthesize a series of new benzoxazole-based pyrazoline derivatives. In vitro antitubercular evaluation against Mycobacterium tuberculosis H(37)Rv and multidrug-resistant TB (MDR-TB) strains showed that most of the target compounds displayed potent activity (MIC similar to 0.625-25 mu g/mL). Few compounds were found to be better than isoniazid against MDR-TB (MIC = 3.25 mu g/mL). In order to gain insights into the plausible binding motifs, the target compounds were docked into enoyl-acyl carrier protein (ACP) reductase, a molecular target of isoniazid. Many compounds were successfully docked into the active site of enoyl-ACP reductase and all the docked compounds occupied the same hydrophobic binding pocket and interacted mostly by dispersion interactions with the neighboring residues Met103, Met155, Tyr158, Met199, Ile202, Ile215, and Leu218. Contribution of the thr

Název v anglickém jazyce

Discovery of new antitubercular agents by combining pyrazoline and benzoxazole pharmacophores: design, synthesis and insights into the binding interactions

Popis výsledku anglicky

The present study is aimed at combining two well-known pharmacophores (pyrazoline and benzoxazole nucleus) to design and synthesize a series of new benzoxazole-based pyrazoline derivatives. In vitro antitubercular evaluation against Mycobacterium tuberculosis H(37)Rv and multidrug-resistant TB (MDR-TB) strains showed that most of the target compounds displayed potent activity (MIC similar to 0.625-25 mu g/mL). Few compounds were found to be better than isoniazid against MDR-TB (MIC = 3.25 mu g/mL). In order to gain insights into the plausible binding motifs, the target compounds were docked into enoyl-acyl carrier protein (ACP) reductase, a molecular target of isoniazid. Many compounds were successfully docked into the active site of enoyl-ACP reductase and all the docked compounds occupied the same hydrophobic binding pocket and interacted mostly by dispersion interactions with the neighboring residues Met103, Met155, Tyr158, Met199, Ile202, Ile215, and Leu218. Contribution of the thr

Druh

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

CEP obor

CC - Organická chemie

OECD FORD obor

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Projekt

—

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2014

Kód důvěrnosti údajů

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

Název periodika

Medicinal Chemistry Research

ISSN

1054-2523

e-ISSN

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Svazek periodika

23

Číslo periodika v rámci svazku

5

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

11

Strana od-do

2218-2228

Kód UT WoS článku

000332153800007

EID výsledku v databázi Scopus

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