Synthesis of Novel Pyrazinamide Derivatives Based on 3-Chloropyrazine-2-carboxamide and Their Antimicrobial Evaluation

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11160%2F17%3A10364271" target="_blank" >RIV/00216208:11160/17:10364271 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/00179906:_____/17:10364271

Výsledek na webu

<a href="http://www.mdpi.com/1420-3049/22/2/223/htm" target="_blank" >http://www.mdpi.com/1420-3049/22/2/223/htm</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.3390/molecules22020223" target="_blank" >10.3390/molecules22020223</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Synthesis of Novel Pyrazinamide Derivatives Based on 3-Chloropyrazine-2-carboxamide and Their Antimicrobial Evaluation

Popis výsledku v původním jazyce

Aminodehalogenation of 3-chloropyrazine-2-carboxamide with variously substituted benzylamines yielded a series of fifteen 3-benzylaminopyrazine-2-carboxamides. Four compounds possessed in vitro whole cell activity against Mycobacterium tuberculosis H37R(v) that was at least equivalent to that of the standard pyrazinamide. MIC values ranged from 6 to 42 mu M. The best MIC (6 mu M) was displayed by 3-[(4-methylbenzyl)amino]pyrazine-2-carboxamide (8) that also showed low cytotoxicity in the HepG2 cell line (IC50 &gt;= 250 mu M). Only moderate activity against Enterococcus faecalis and Staphylococcus aureus was observed. No activity was detected against any of tested fungal strains. Molecular docking with mycobacterial enoyl-ACP reductase (InhA) was performed to investigate the possible target of the prepared compounds. Active compounds shared common binding interactions of known InhA inhibitors. Antimycobacterial activity of the title compounds was compared to the previously published benzylamino-substituted pyrazines with differing substitution on the pyrazine core (carbonitrile moiety). The title series possessed comparable activity and lower cytotoxicity than molecules containing a carbonitrile group on the pyrazine ring.

Název v anglickém jazyce

Synthesis of Novel Pyrazinamide Derivatives Based on 3-Chloropyrazine-2-carboxamide and Their Antimicrobial Evaluation

Popis výsledku anglicky

Aminodehalogenation of 3-chloropyrazine-2-carboxamide with variously substituted benzylamines yielded a series of fifteen 3-benzylaminopyrazine-2-carboxamides. Four compounds possessed in vitro whole cell activity against Mycobacterium tuberculosis H37R(v) that was at least equivalent to that of the standard pyrazinamide. MIC values ranged from 6 to 42 mu M. The best MIC (6 mu M) was displayed by 3-[(4-methylbenzyl)amino]pyrazine-2-carboxamide (8) that also showed low cytotoxicity in the HepG2 cell line (IC50 &gt;= 250 mu M). Only moderate activity against Enterococcus faecalis and Staphylococcus aureus was observed. No activity was detected against any of tested fungal strains. Molecular docking with mycobacterial enoyl-ACP reductase (InhA) was performed to investigate the possible target of the prepared compounds. Active compounds shared common binding interactions of known InhA inhibitors. Antimycobacterial activity of the title compounds was compared to the previously published benzylamino-substituted pyrazines with differing substitution on the pyrazine core (carbonitrile moiety). The title series possessed comparable activity and lower cytotoxicity than molecules containing a carbonitrile group on the pyrazine ring.

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/GJ17-27514Y" target="_blank" >GJ17-27514Y: Peptidové drug delivery systémy směrované do makrofágů pro antimykobakteriálně aktivní sloučeniny</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

Molecules

ISSN

1420-3049

e-ISSN

—

Svazek periodika

22

Číslo periodika v rámci svazku

2

Stát vydavatele periodika

CH - Švýcarská konfederace

Počet stran výsledku

20

Strana od-do

—

Kód UT WoS článku

000395552400037

EID výsledku v databázi Scopus

2-s2.0-85013997060