Surface screening, molecular modeling and in vitro studies on the interactions of aflatoxin M1 and human enzymes acetyl- and butyrylcholinesterase

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F62690094%3A18470%2F19%3A50015658" target="_blank" >RIV/62690094:18470/19:50015658 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/60162694:G44__/19:00537491 RIV/62690094:18450/19:50015658

Výsledek na webu

<a href="https://www.sciencedirect.com/science/article/pii/S0009279719303357?via%3Dihub" target="_blank" >https://www.sciencedirect.com/science/article/pii/S0009279719303357?via%3Dihub</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1016/j.cbi.2019.05.022" target="_blank" >10.1016/j.cbi.2019.05.022</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Surface screening, molecular modeling and in vitro studies on the interactions of aflatoxin M1 and human enzymes acetyl- and butyrylcholinesterase

Popis výsledku v původním jazyce

Aflatoxin M1 (AFM1) is a mycotoxin produced by Aspergillus fungi and found in contaminated milk, breastfeed and dairy products, being highly toxic and carcinogenic to humans and other mammalian species. It is also produced in the human body as a metabolite of aflatoxin B1 (AFB1), one of the most toxic natural products known. Previous studies have shown that AFM1 is a potential inhibitor of the enzyme acetylcholinesterase (AChE), and therefore, a potential neurotoxic agent. In this work, surface screening (SS) and molecular dynamics (MD) simulation on human acetylcholinesterase AChE (HssAChE) were performed to corroborate literature data regarding preferential binding sites and type of inhibition. Also, an inedited theoretical study on the interactions of AFM1 with human butyrylcholinesterase (HssBChE) was performed. In vitro inhibition tests on both enzymes were done to support theoretical results. MD simulations suggested the catalytic anionic site of HssAChE as the preferential binding site for AFM1 and also that this metabolite is not a good inhibitor of HssBChE, corroborating previous studies. In vitro assays also corroborated molecular modeling studies by showing that AFM1 did not inhibit BChE and was able to inhibit AChE, although not as much as AFB1.

Název v anglickém jazyce

Surface screening, molecular modeling and in vitro studies on the interactions of aflatoxin M1 and human enzymes acetyl- and butyrylcholinesterase

Popis výsledku anglicky

Aflatoxin M1 (AFM1) is a mycotoxin produced by Aspergillus fungi and found in contaminated milk, breastfeed and dairy products, being highly toxic and carcinogenic to humans and other mammalian species. It is also produced in the human body as a metabolite of aflatoxin B1 (AFB1), one of the most toxic natural products known. Previous studies have shown that AFM1 is a potential inhibitor of the enzyme acetylcholinesterase (AChE), and therefore, a potential neurotoxic agent. In this work, surface screening (SS) and molecular dynamics (MD) simulation on human acetylcholinesterase AChE (HssAChE) were performed to corroborate literature data regarding preferential binding sites and type of inhibition. Also, an inedited theoretical study on the interactions of AFM1 with human butyrylcholinesterase (HssBChE) was performed. In vitro inhibition tests on both enzymes were done to support theoretical results. MD simulations suggested the catalytic anionic site of HssAChE as the preferential binding site for AFM1 and also that this metabolite is not a good inhibitor of HssBChE, corroborating previous studies. In vitro assays also corroborated molecular modeling studies by showing that AFM1 did not inhibit BChE and was able to inhibit AChE, although not as much as AFB1.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30107 - Medicinal chemistry

Projekt

<a href="/cs/project/GA18-01734S" target="_blank" >GA18-01734S: Reaktivátory butyrylcholinesterasy pro přípravu pseudo-katalytických scavengerů využitelných při intoxikacích organofosforovými sloučeninami</a><br>

Návaznosti

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Rok uplatnění

2019

Kód důvěrnosti údajů

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

Název periodika

Chemico-biological interactions

ISSN

0009-2797

e-ISSN

—

Svazek periodika

308

Číslo periodika v rámci svazku

Aug

Stát vydavatele periodika

IE - Irsko

Počet stran výsledku

7

Strana od-do

113-119

Kód UT WoS článku

000474214200012

EID výsledku v databázi Scopus

2-s2.0-85066079621