A comprehensive structural analysis of new antimalarial derivatives using chiroptical and vibrational spectoscopy

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F60461373%3A22310%2F23%3A43927307" target="_blank" >RIV/60461373:22310/23:43927307 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/60461373:22340/23:43927307

Výsledek na webu

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DOI - Digital Object Identifier

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Jazyk výsledku

angličtina

Název v původním jazyce

A comprehensive structural analysis of new antimalarial derivatives using chiroptical and vibrational spectoscopy

Popis výsledku v původním jazyce

One of the most effective and affordable drug used in prevention and as a standard drug in the chemoprophylaxis andtreatment of malaria is rac-erythro-mefloquine hydrochloride, commercialized as Lariam® [1]. This molecule is known as achiral and their stereochemistry not only affects antimalarial activity [2, 3] but also leads to different adverse effects of therespective enantiomers [4]. In recent years, it has been shown that the efficacy of most antimalarials is compromised by theemergence of Plasmodium species resistant to available antimalarials [5]. Resistance has been reported with almost all avail-able antimalarials, has reinforced the urgent need to develop new antimalarials against resistant strains.In this study, we have developed a chiral liquid chromatography method using a polysaccharide chiral stationary phase toseparate the corresponding enantiomers of all prepared antimalarial candidates. We utilized molecular spectroscopic meth-ods including chiroptical (electronic circular dichroism and vibrational circular dichroism) and non-polarizable (infrared andultraviolet absorption) spectroscopies. In combination with density functional theory calculations, we have obtained stableconformers of selected enantiomers in solution and their relative abundances, which we used to simulate their spectra. Theexperimental and calculated data have been used to elucidate the 3D structure of the enantiomerically pure compounds andassign the absolute configuration of all prepared compounds.

Název v anglickém jazyce

A comprehensive structural analysis of new antimalarial derivatives using chiroptical and vibrational spectoscopy

Popis výsledku anglicky

One of the most effective and affordable drug used in prevention and as a standard drug in the chemoprophylaxis andtreatment of malaria is rac-erythro-mefloquine hydrochloride, commercialized as Lariam® [1]. This molecule is known as achiral and their stereochemistry not only affects antimalarial activity [2, 3] but also leads to different adverse effects of therespective enantiomers [4]. In recent years, it has been shown that the efficacy of most antimalarials is compromised by theemergence of Plasmodium species resistant to available antimalarials [5]. Resistance has been reported with almost all avail-able antimalarials, has reinforced the urgent need to develop new antimalarials against resistant strains.In this study, we have developed a chiral liquid chromatography method using a polysaccharide chiral stationary phase toseparate the corresponding enantiomers of all prepared antimalarial candidates. We utilized molecular spectroscopic meth-ods including chiroptical (electronic circular dichroism and vibrational circular dichroism) and non-polarizable (infrared andultraviolet absorption) spectroscopies. In combination with density functional theory calculations, we have obtained stableconformers of selected enantiomers in solution and their relative abundances, which we used to simulate their spectra. Theexperimental and calculated data have been used to elucidate the 3D structure of the enantiomerically pure compounds andassign the absolute configuration of all prepared compounds.

Druh

O - Ostatní výsledky

CEP obor

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OECD FORD obor

10406 - Analytical chemistry

Projekt

<a href="/cs/project/VJ01010043" target="_blank" >VJ01010043: Pharmacrime – forenzní identifikace prohormonů a padělků léčiv</a><br>

Návaznosti

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

Rok uplatnění

2023

Kód důvěrnosti údajů

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