Synthesis, absolute configuration and in vitro cytotoxicity of deschloroketamine enantiomers: rediscovered and abused dissociative anaesthetic

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F60461373%3A22310%2F18%3A43916571" target="_blank" >RIV/60461373:22310/18:43916571 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/60461373:22330/18:43916571 RIV/60461373:22340/18:43916571 RIV/60461373:22810/18:43916571

Výsledek na webu

<a href="http://dx.doi.org/10.1039/c8nj03107j" target="_blank" >http://dx.doi.org/10.1039/c8nj03107j</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1039/c8nj03107j" target="_blank" >10.1039/c8nj03107j</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Synthesis, absolute configuration and in vitro cytotoxicity of deschloroketamine enantiomers: rediscovered and abused dissociative anaesthetic

Popis výsledku v původním jazyce

In this study, we aim to determine differences in cytotoxicity of racemic deschloroketamine and its enantiomers. The synthesized racemate of this recently rediscovered and abused dissociative anaesthetic was resolved by chiral HPLC and the absolute configuration of the enantiomers was assigned using a combination of circular dichroism methods and single-crystal X-ray. Not only the absolute configuration, but also the most preferred conformers present in the crystal were successfully determined by electron and vibrational circular dichroism supported by ab initio calculations, and confirmed by X-ray. The in vitro cytotoxicity of racemic deschloroketamine and its enantiomers was determined for nine different types of cell lines. Generally, (S)-deschloroketamine exhibited higher cytotoxicity in the majority of cases. For human embryonic kidney cells (HEK 293T), the (S)-enantiomer reached the IC50 below 1 mM concentration and, in consequence, proved to be twice as potent as the (R)-enantiomer. On the other hand, live-cell fluorescence microscopy imaging at sub-IC50 concentrations provided evidence for only a minor effect of deschloroketamine racemate and enantiomers on endoplasmic reticulum stress and mitochondria morphology in neuroblastoma cells SH-SY5Y. © The Royal Society of Chemistry and the Centre National de la Recherche Scientifique.

Název v anglickém jazyce

Synthesis, absolute configuration and in vitro cytotoxicity of deschloroketamine enantiomers: rediscovered and abused dissociative anaesthetic

Popis výsledku anglicky

In this study, we aim to determine differences in cytotoxicity of racemic deschloroketamine and its enantiomers. The synthesized racemate of this recently rediscovered and abused dissociative anaesthetic was resolved by chiral HPLC and the absolute configuration of the enantiomers was assigned using a combination of circular dichroism methods and single-crystal X-ray. Not only the absolute configuration, but also the most preferred conformers present in the crystal were successfully determined by electron and vibrational circular dichroism supported by ab initio calculations, and confirmed by X-ray. The in vitro cytotoxicity of racemic deschloroketamine and its enantiomers was determined for nine different types of cell lines. Generally, (S)-deschloroketamine exhibited higher cytotoxicity in the majority of cases. For human embryonic kidney cells (HEK 293T), the (S)-enantiomer reached the IC50 below 1 mM concentration and, in consequence, proved to be twice as potent as the (R)-enantiomer. On the other hand, live-cell fluorescence microscopy imaging at sub-IC50 concentrations provided evidence for only a minor effect of deschloroketamine racemate and enantiomers on endoplasmic reticulum stress and mitochondria morphology in neuroblastoma cells SH-SY5Y. © The Royal Society of Chemistry and the Centre National de la Recherche Scientifique.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10401 - Organic chemistry

Projekt

<a href="/cs/project/GJ16-17689Y" target="_blank" >GJ16-17689Y: Nové chirální stacionární fáze ionexové povahy pro enantiomerní separace</a><br>

Návaznosti

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

Rok uplatnění

2018

Kód důvěrnosti údajů

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

Název periodika

New Journal of Chemistry

ISSN

1144-0546

e-ISSN

—

Svazek periodika

42

Číslo periodika v rámci svazku

24

Stát vydavatele periodika

GB - Spojené království Velké Británie a Severního Irska

Počet stran výsledku

9

Strana od-do

19360-19368

Kód UT WoS článku

000456501100006

EID výsledku v databázi Scopus

2-s2.0-85057715599