Design, Synthesis, Antimycobacterial Evaluation, and In Silico Studies of 3-(Phenylcarbamoyl)-pyrazine-2-carboxylic Acids

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00179906%3A_____%2F17%3A10365045" target="_blank" >RIV/00179906:_____/17:10365045 - isvavai.cz</a>

Alternative codes found

RIV/00216208:11160/17:10365045

Result on the web

<a href="http://www.mdpi.com/1420-3049/22/9/1491/htm" target="_blank" >http://www.mdpi.com/1420-3049/22/9/1491/htm</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.3390/molecules22091491" target="_blank" >10.3390/molecules22091491</a>

Result language

angličtina

Original language name

Design, Synthesis, Antimycobacterial Evaluation, and In Silico Studies of 3-(Phenylcarbamoyl)-pyrazine-2-carboxylic Acids

Original language description

Pyrazinamide, the first-line antitubercular drug, has been regarded the basic component of tuberculosis treatment for over sixty years. Researchers have investigated its effect on Mycobacterium tuberculosis for this long time, and as a result, new potential targets of pyrazinamide or its active form, pyrazinoic acid, have been found. We have designed and prepared 3-(phenyl-carbamoyl) pyrazine-2-carboxylic acids as more lipophilic derivatives of pyrazinoic acid. We also prepared methyl and propyl derivatives as prodrugs with further increased lipophilicity. Antimycobacterial, antibacterial and antifungal growth inhibiting activity was investigated in all prepared compounds. 3-[(4-Nitrophenyl) carbamoyl] pyrazine-2-carboxylic acid (16) exerted high antimycobacterial activity against Mycobacterium tuberculosis H37Rv with MIC = 1.56 mu g.mL(-1) (5 mu M). Propyl 3-{[4-(trifluoromethyl)phenyl] carbamoyl} pyrazine-2-carboxylate (18a) showed also high antimycobacterial activity against Mycobacterium tuberculosis H37Rv with MIC = 3.13 mu g.mL(-1). In vitro cytotoxicity of the active compounds was investigated and no significant cytotoxic effect was observed. Based to structural similarity to known inhibitors of decaprenylphosphoryl-beta-D-ribose oxidase, DprE1, we performed molecular docking of the prepared acids to DprE1. These in silico experiments indicate that modification of the linker connecting aromatic parts of molecule does not have any negative influence on the binding.

Czech name

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Czech description

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Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

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OECD FORD branch

30104 - Pharmacology and pharmacy

Project

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Continuities

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year

2017

Confidentiality

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

Name of the periodical

Molecules

ISSN

1420-3049

e-ISSN

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Volume of the periodical

22

Issue of the periodical within the volume

9

Country of publishing house

CH - SWITZERLAND

Number of pages

17

Pages from-to

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UT code for WoS article

000411499400086

EID of the result in the Scopus database

2-s2.0-85029660516