Biological Activities and ADMET-Related Properties of Novel Set of Cinnamanilides

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61989592%3A15310%2F20%3A73604497" target="_blank" >RIV/61989592:15310/20:73604497 - isvavai.cz</a>

Výsledek na webu

<a href="https://www.mdpi.com/1420-3049/25/18/4121/htm" target="_blank" >https://www.mdpi.com/1420-3049/25/18/4121/htm</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.3390/molecules25184121" target="_blank" >10.3390/molecules25184121</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Biological Activities and ADMET-Related Properties of Novel Set of Cinnamanilides

Popis výsledku v původním jazyce

A series of nineteen novel ring-substitutedN-arylcinnamanilides was synthesized and characterized. All investigated compounds were tested againstStaphylococcus aureusas the reference strain, two clinical isolates of methicillin-resistantS. aureus(MRSA), andMycobacterium tuberculosis. (2E)-N-[3-Fluoro-4-(trifluoromethyl)phenyl]-3-phenylprop-2-enamide showed even better activity (minimum inhibitory concentration (MIC) 25.9 and 12.9 mu M) against MRSA isolates than the commonly used ampicillin (MIC 45.8 mu M). The screening of the cell viability was performed using THP1-Blue (TM) NF-kappa B cells and, except for (2E)-N-(4-bromo-3-chlorophenyl)-3-phenylprop-2-enamide (IC(50)6.5 mu M), none of the discussed compounds showed any significant cytotoxic effect up to 20 mu M. Moreover, all compounds were tested for their anti-inflammatory potential; several compounds attenuated the lipopolysaccharide-induced NF-kappa B activation and were more potent than the parental cinnamic acid. The lipophilicity values were specified experimentally as well. In addition, in silico approximation of the lipophilicity values was performed employing a set of free/commercial clogP estimators, corrected afterwards by the corresponding pK(a)calculated at physiological pH and subsequently cross-compared with the experimental parameters. The similarity-driven property space evaluation of structural analogs was carried out using the principal component analysis, Tanimoto metrics, and Kohonen mapping.

Název v anglickém jazyce

Biological Activities and ADMET-Related Properties of Novel Set of Cinnamanilides

Popis výsledku anglicky

A series of nineteen novel ring-substitutedN-arylcinnamanilides was synthesized and characterized. All investigated compounds were tested againstStaphylococcus aureusas the reference strain, two clinical isolates of methicillin-resistantS. aureus(MRSA), andMycobacterium tuberculosis. (2E)-N-[3-Fluoro-4-(trifluoromethyl)phenyl]-3-phenylprop-2-enamide showed even better activity (minimum inhibitory concentration (MIC) 25.9 and 12.9 mu M) against MRSA isolates than the commonly used ampicillin (MIC 45.8 mu M). The screening of the cell viability was performed using THP1-Blue (TM) NF-kappa B cells and, except for (2E)-N-(4-bromo-3-chlorophenyl)-3-phenylprop-2-enamide (IC(50)6.5 mu M), none of the discussed compounds showed any significant cytotoxic effect up to 20 mu M. Moreover, all compounds were tested for their anti-inflammatory potential; several compounds attenuated the lipopolysaccharide-induced NF-kappa B activation and were more potent than the parental cinnamic acid. The lipophilicity values were specified experimentally as well. In addition, in silico approximation of the lipophilicity values was performed employing a set of free/commercial clogP estimators, corrected afterwards by the corresponding pK(a)calculated at physiological pH and subsequently cross-compared with the experimental parameters. The similarity-driven property space evaluation of structural analogs was carried out using the principal component analysis, Tanimoto metrics, and Kohonen mapping.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30107 - Medicinal chemistry

Projekt

—

Návaznosti

S - Specificky vyzkum na vysokych skolach

Rok uplatnění

2020

Kód důvěrnosti údajů

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

Název periodika

MOLECULES

ISSN

1420-3049

e-ISSN

—

Svazek periodika

25

Číslo periodika v rámci svazku

18

Stát vydavatele periodika

CH - Švýcarská konfederace

Počet stran výsledku

23

Strana od-do

"4121-1"-"4121-23"

Kód UT WoS článku

000580723700001

EID výsledku v databázi Scopus

2-s2.0-85090844501