Novel Aminoguanidine Hydrazone Analogues: From Potential Antimicrobial Agents to Potent Cholinesterase Inhibitors

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11160%2F21%3A10434684" target="_blank" >RIV/00216208:11160/21:10434684 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/00216275:25310/21:39917729 RIV/44555601:13440/21:43896432

Výsledek na webu

<a href="https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=MjlnDZgxJQ" target="_blank" >https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=MjlnDZgxJQ</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.3390/ph14121229" target="_blank" >10.3390/ph14121229</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Novel Aminoguanidine Hydrazone Analogues: From Potential Antimicrobial Agents to Potent Cholinesterase Inhibitors

Popis výsledku v původním jazyce

A series of thirty-one hydrazones of aminoguanidine, nitroaminoguanidine, 1,3-diaminoguanidine, and (thio)semicarbazide were prepared from various aldehydes, mainly chlorobenzaldehydes, halogenated salicylaldehydes, 5-nitrofurfural, and isatin (yields of 50-99%). They were characterized by spectral methods. Primarily, they were designed and evaluated as potential broad-spectrum antimicrobial agents. The compounds were effective against Gram-positive bacteria including methicillin-resistant Staphylococcus aureus with minimum inhibitory concentrations (MIC) from 7.8 mu M, as well as Gram-negative strains with higher MIC. Antifungal evaluation against yeasts and Trichophyton mentagrophytes found MIC from 62.5 mu M. We also evaluated inhibition of acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE). The compounds inhibited both enzymes with IC50 values of 17.95-54.93 mu M for AChE and &gt;=1.69 mu M for BuChE. Based on the substitution, it is possible to modify selectivity for a particular cholinesterase as we obtained selective inhibitors of either AChE or BuChE, as well as balanced inhibitors. The compounds act via mixed-type inhibition. Their interactions with enzymes were studied by molecular docking. Cytotoxicity was assessed in HepG2 cells. The hydrazones differ in their toxicity (IC50 from 5.27 to &gt;500 mu M). Some of the derivatives represent promising hits for further development. Based on the substitution pattern, it is possible to modulate bioactivity to the desired one.

Název v anglickém jazyce

Novel Aminoguanidine Hydrazone Analogues: From Potential Antimicrobial Agents to Potent Cholinesterase Inhibitors

Popis výsledku anglicky

A series of thirty-one hydrazones of aminoguanidine, nitroaminoguanidine, 1,3-diaminoguanidine, and (thio)semicarbazide were prepared from various aldehydes, mainly chlorobenzaldehydes, halogenated salicylaldehydes, 5-nitrofurfural, and isatin (yields of 50-99%). They were characterized by spectral methods. Primarily, they were designed and evaluated as potential broad-spectrum antimicrobial agents. The compounds were effective against Gram-positive bacteria including methicillin-resistant Staphylococcus aureus with minimum inhibitory concentrations (MIC) from 7.8 mu M, as well as Gram-negative strains with higher MIC. Antifungal evaluation against yeasts and Trichophyton mentagrophytes found MIC from 62.5 mu M. We also evaluated inhibition of acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE). The compounds inhibited both enzymes with IC50 values of 17.95-54.93 mu M for AChE and &gt;=1.69 mu M for BuChE. Based on the substitution, it is possible to modify selectivity for a particular cholinesterase as we obtained selective inhibitors of either AChE or BuChE, as well as balanced inhibitors. The compounds act via mixed-type inhibition. Their interactions with enzymes were studied by molecular docking. Cytotoxicity was assessed in HepG2 cells. The hydrazones differ in their toxicity (IC50 from 5.27 to &gt;500 mu M). Some of the derivatives represent promising hits for further development. Based on the substitution pattern, it is possible to modulate bioactivity to the desired one.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30104 - Pharmacology and pharmacy

Projekt

Výsledek vznikl pri realizaci vícero projektů. Více informací v záložce Projekty.

Návaznosti

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

Rok uplatnění

2021

Kód důvěrnosti údajů

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

Název periodika

Pharmaceuticals

ISSN

1424-8247

e-ISSN

—

Svazek periodika

14

Číslo periodika v rámci svazku

12

Stát vydavatele periodika

CH - Švýcarská konfederace

Počet stran výsledku

30

Strana od-do

1229

Kód UT WoS článku

000736899500001

EID výsledku v databázi Scopus

2-s2.0-85120402403