Synthesis of Readily Available Fluorophenylalanine Derivatives and Investigation of Their Biological Activity

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216275%3A25310%2F17%3A39910632" target="_blank" >RIV/00216275:25310/17:39910632 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/00216208:11160/17:10365384 RIV/71009396:_____/17:N0000005

Výsledek na webu

<a href="https://doi.org/10.1016/j.bioorg.2017.02.010" target="_blank" >https://doi.org/10.1016/j.bioorg.2017.02.010</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1016/j.bioorg.2017.02.010" target="_blank" >10.1016/j.bioorg.2017.02.010</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Synthesis of Readily Available Fluorophenylalanine Derivatives and Investigation of Their Biological Activity

Popis výsledku v původním jazyce

A series of thirty novel N-acetylated fluorophenylalanine-based aromatic amides and esters was synthesized using N-(3-dimethylaminopropyl)-N0-ethylcarbodiimide or phosphorus trichloride in pyridine. They were characterized by spectral methods and screened against various microbes (Mycobacterium tuberculosis, non-tuberculous mycobacteria, other bacteria, fungi), for their inhibition of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) and cytotoxicity. All amino acids derivatives revealed a moderate inhibition of both cholinesterases with IC50 values for AChE and BChE of 57.88–130.75 mM and 8.25–289.0 mM, respectively. Some derivatives were comparable or superior to rivastigmine, an established drug. Phenyl 2-acetamido-3-(4-fluorophenyl)propanoate was identified as the selective and most potent inhibitor of BChE. The esterification and amidation of parent acids led to an improved BChE inhibition. The esters are better inhibitors of BChE than the amides. The introduction of NO2 and CH3 groups into aniline ring and CF3 moiety in phenol is translated into lower IC50 values. Seven compounds showed selectivity index higher than 10 for at least one cholinesterase. Especially the esters exhibited a mild activity against Gram-positive bacteria, mycobacteria and several fungal strains with minimum inhibitory concentrations starting from 125 mM. The highest susceptibility was recorded for Trichophyton mentagrophytes fungus.

Název v anglickém jazyce

Synthesis of Readily Available Fluorophenylalanine Derivatives and Investigation of Their Biological Activity

Popis výsledku anglicky

A series of thirty novel N-acetylated fluorophenylalanine-based aromatic amides and esters was synthesized using N-(3-dimethylaminopropyl)-N0-ethylcarbodiimide or phosphorus trichloride in pyridine. They were characterized by spectral methods and screened against various microbes (Mycobacterium tuberculosis, non-tuberculous mycobacteria, other bacteria, fungi), for their inhibition of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) and cytotoxicity. All amino acids derivatives revealed a moderate inhibition of both cholinesterases with IC50 values for AChE and BChE of 57.88–130.75 mM and 8.25–289.0 mM, respectively. Some derivatives were comparable or superior to rivastigmine, an established drug. Phenyl 2-acetamido-3-(4-fluorophenyl)propanoate was identified as the selective and most potent inhibitor of BChE. The esterification and amidation of parent acids led to an improved BChE inhibition. The esters are better inhibitors of BChE than the amides. The introduction of NO2 and CH3 groups into aniline ring and CF3 moiety in phenol is translated into lower IC50 values. Seven compounds showed selectivity index higher than 10 for at least one cholinesterase. Especially the esters exhibited a mild activity against Gram-positive bacteria, mycobacteria and several fungal strains with minimum inhibitory concentrations starting from 125 mM. The highest susceptibility was recorded for Trichophyton mentagrophytes fungus.

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

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2017

Kód důvěrnosti údajů

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

Název periodika

Bioorganic Chemistry

ISSN

0045-2068

e-ISSN

—

Svazek periodika

71

Číslo periodika v rámci svazku

April

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

13

Strana od-do

244-256

Kód UT WoS článku

000404534300025

EID výsledku v databázi Scopus

—