Searching for New Antimicrobial Agents by Targeting Bacterial NAD Metabolism: Evaluation of Frentizole Derivatives Selected by Molecular Docking

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F60162694%3AG44__%2F20%3A00555751" target="_blank" >RIV/60162694:G44__/20:00555751 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/62690094:18470/20:50016894 RIV/00179906:_____/20:10411778

Výsledek na webu

<a href="https://www.mmsl.cz/artkey/mms-202002-0002_searching-for-new-antimicrobial-agents-by-targeting-bacterial-nad-metabolism-evaluation-of-frentizole-derivati.php" target="_blank" >https://www.mmsl.cz/artkey/mms-202002-0002_searching-for-new-antimicrobial-agents-by-targeting-bacterial-nad-metabolism-evaluation-of-frentizole-derivati.php</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.31482/mmsl.2020.005" target="_blank" >10.31482/mmsl.2020.005</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Searching for New Antimicrobial Agents by Targeting Bacterial NAD Metabolism: Evaluation of Frentizole Derivatives Selected by Molecular Docking

Popis výsledku v původním jazyce

Growing evidence of antibiotic-resistant pathogens is a serious medical issue that has to be addressed. Our antimicrobial research is focused on searching for novel small molecules that differ from the most clinically used antibiotics by chemical structure and mechanism. However, this fundamental research is like looking for a needle in a haystack. In addition, in vitro methods are time-consuming and expensive to screen large number of compounds in reasonable time. Off-target screening can represent a solution to find novel and effective antimicrobial agents that can eliminate these problems. Accordingly, molecular docking in the family of selected frentizole derivatives predicted their potential to inhibit bacterial nicotinate mononucleotide adenylyltransferase (NadD). This bacterial-essential specific enzyme has an important role in NAD metabolism. Thus, underlying mechanism of antimicrobials derived from frentizole would be interference with this biochemical process. Unfortunately, broth microdilution assay did not display any antimicrobial activity of tested compounds. On the other hand, herein we propose that off-target screening can facilitate searching for new drugs and that NadD could be a relevant target for antimicrobials.

Název v anglickém jazyce

Searching for New Antimicrobial Agents by Targeting Bacterial NAD Metabolism: Evaluation of Frentizole Derivatives Selected by Molecular Docking

Popis výsledku anglicky

Growing evidence of antibiotic-resistant pathogens is a serious medical issue that has to be addressed. Our antimicrobial research is focused on searching for novel small molecules that differ from the most clinically used antibiotics by chemical structure and mechanism. However, this fundamental research is like looking for a needle in a haystack. In addition, in vitro methods are time-consuming and expensive to screen large number of compounds in reasonable time. Off-target screening can represent a solution to find novel and effective antimicrobial agents that can eliminate these problems. Accordingly, molecular docking in the family of selected frentizole derivatives predicted their potential to inhibit bacterial nicotinate mononucleotide adenylyltransferase (NadD). This bacterial-essential specific enzyme has an important role in NAD metabolism. Thus, underlying mechanism of antimicrobials derived from frentizole would be interference with this biochemical process. Unfortunately, broth microdilution assay did not display any antimicrobial activity of tested compounds. On the other hand, herein we propose that off-target screening can facilitate searching for new drugs and that NadD could be a relevant target for antimicrobials.

Druh

J_SC - Článek v periodiku v databázi SCOPUS

CEP obor

—

OECD FORD obor

30107 - Medicinal chemistry

Projekt

<a href="/cs/project/NV18-09-00181" target="_blank" >NV18-09-00181: Vývoj polyvalentního dekontaminačního činidla</a><br>

Návaznosti

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)<br>S - Specificky vyzkum na vysokych skolach<br>I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2020

Kód důvěrnosti údajů

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

Název periodika

Military Medical Science Letters

ISSN

0372-7025

e-ISSN

2571-113X

Svazek periodika

89

Číslo periodika v rámci svazku

2

Stát vydavatele periodika

CZ - Česká republika

Počet stran výsledku

8

Strana od-do

66-73

Kód UT WoS článku

—

EID výsledku v databázi Scopus

2-s2.0-85086029676