4-Isobutylmethcathinone—A Novel Synthetic Cathinone with High In Vitro Cytotoxicity and Strong Receptor Binding Preference of Enantiomers

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F60461373%3A22310%2F22%3A43925247" target="_blank" >RIV/60461373:22310/22:43925247 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/60461373:22330/22:43925247 RIV/60461373:22340/22:43925247 RIV/60461373:22810/22:43925247

Výsledek na webu

<a href="https://www.mdpi.com/1424-8247/15/12/1495" target="_blank" >https://www.mdpi.com/1424-8247/15/12/1495</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.3390/ph15121495" target="_blank" >10.3390/ph15121495</a>

Jazyk výsledku

angličtina

Název v původním jazyce

4-Isobutylmethcathinone—A Novel Synthetic Cathinone with High In Vitro Cytotoxicity and Strong Receptor Binding Preference of Enantiomers

Popis výsledku v původním jazyce

New psychoactive substances and among them synthetic cathinones represent a significant threat to human health globally. However, within such a large pool of substances derived from a natural compound ((S)-cathinone), substances with important pharmaceutical uses can be identified, as already documented by bupropione. Therefore, this work aimed to find a synthetic pathway for a novel synthetic cathinone, namely 4-isobutylmethcathinone, and describe its spectroscopic properties and biological activity in vitro. Since cathinones comprise a chiral center in their structure, a method for chiral separation of the substance was elaborated using high-performance liquid chromatography on an analytical and preparative scale. Preparative enantioseparation on a polysaccharide column provided a sufficient amount of the drug for the chiroptical studies leading to the determination of the absolute configuration of enantiomers as well as for their subsequent in vitro cytotoxicity study. The cytotoxicity induced by 4-isobutylmethcathinone was determined in human cells derived from the urinary bladder (5637), neuroblastoma (SH-SY5Y), microglia (HMC-3), and hepatocellular carcinoma (Hep G2), in which the IC50 values after 72 h reached an 18–65 µM concentration. This is significantly higher cytotoxicity in comparison with other synthetic cathinones. In the receptor binding studies, a significant difference in the agonistic effect on dopamine and adrenergic receptors of individual enantiomers was observed. The lack of binding affinity towards the serotonin receptors then relates 4-isobutylmethcathinone to the family of monoamine drugs, such as 3,4-methylenedioxymathamphetamine (ecstasy, MDMA). © 2022 by the authors.

Název v anglickém jazyce

4-Isobutylmethcathinone—A Novel Synthetic Cathinone with High In Vitro Cytotoxicity and Strong Receptor Binding Preference of Enantiomers

Popis výsledku anglicky

New psychoactive substances and among them synthetic cathinones represent a significant threat to human health globally. However, within such a large pool of substances derived from a natural compound ((S)-cathinone), substances with important pharmaceutical uses can be identified, as already documented by bupropione. Therefore, this work aimed to find a synthetic pathway for a novel synthetic cathinone, namely 4-isobutylmethcathinone, and describe its spectroscopic properties and biological activity in vitro. Since cathinones comprise a chiral center in their structure, a method for chiral separation of the substance was elaborated using high-performance liquid chromatography on an analytical and preparative scale. Preparative enantioseparation on a polysaccharide column provided a sufficient amount of the drug for the chiroptical studies leading to the determination of the absolute configuration of enantiomers as well as for their subsequent in vitro cytotoxicity study. The cytotoxicity induced by 4-isobutylmethcathinone was determined in human cells derived from the urinary bladder (5637), neuroblastoma (SH-SY5Y), microglia (HMC-3), and hepatocellular carcinoma (Hep G2), in which the IC50 values after 72 h reached an 18–65 µM concentration. This is significantly higher cytotoxicity in comparison with other synthetic cathinones. In the receptor binding studies, a significant difference in the agonistic effect on dopamine and adrenergic receptors of individual enantiomers was observed. The lack of binding affinity towards the serotonin receptors then relates 4-isobutylmethcathinone to the family of monoamine drugs, such as 3,4-methylenedioxymathamphetamine (ecstasy, MDMA). © 2022 by the authors.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10406 - Analytical chemistry

Projekt

<a href="/cs/project/GC21-31139J" target="_blank" >GC21-31139J: Nové chirální ionexy pro chromatografické enantioseparace</a><br>

Návaznosti

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

Rok uplatnění

2022

Kód důvěrnosti údajů

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

Název periodika

Pharmaceuticals

ISSN

1424-8247

e-ISSN

1424-8247

Svazek periodika

15

Číslo periodika v rámci svazku

12

Stát vydavatele periodika

CH - Švýcarská konfederace

Počet stran výsledku

17

Strana od-do

nestrankovano

Kód UT WoS článku

000902809200001

EID výsledku v databázi Scopus

2-s2.0-85144738475