X-ray Structure Determination, Antioxidant Voltammetry Studies of Butein and 2′,4′-Dihydroxy-3,4-dimethoxychalcone. Computational Studies of 4 Structurally Related 2′,4′-diOH Chalcones to Examine Their Antimalarial Activity by Binding to Falcipain-2

Malaria is a huge global health burden with resistance to currently available medicines resulting in the search for newer antimalarial compounds from traditional medicinal plants in malaria-endemic regions. Previous studies on two chalcones, homobutein and 5-prenylbutein, present in <i>E. abys...

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Autores principales:	Ijeoma Okoye, Sandra Yu, Francesco Caruso, Miriam Rossi
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	falcipain-2 antioxidant chalcone butein superoxide Organic chemistry QD241-441
Acceso en línea:	https://doaj.org/article/6b0c5d5b6ee944c68c1e0520bd46d2e8
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id	oai:doaj.org-article:6b0c5d5b6ee944c68c1e0520bd46d2e8
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spelling	oai:doaj.org-article:6b0c5d5b6ee944c68c1e0520bd46d2e82021-11-11T18:30:26ZX-ray Structure Determination, Antioxidant Voltammetry Studies of Butein and 2′,4′-Dihydroxy-3,4-dimethoxychalcone. Computational Studies of 4 Structurally Related 2′,4′-diOH Chalcones to Examine Their Antimalarial Activity by Binding to Falcipain-210.3390/molecules262165111420-3049https://doaj.org/article/6b0c5d5b6ee944c68c1e0520bd46d2e82021-10-01T00:00:00Zhttps://www.mdpi.com/1420-3049/26/21/6511https://doaj.org/toc/1420-3049Malaria is a huge global health burden with resistance to currently available medicines resulting in the search for newer antimalarial compounds from traditional medicinal plants in malaria-endemic regions. Previous studies on two chalcones, homobutein and 5-prenylbutein, present in <i>E. abyssinica</i>, have shown moderate antiplasmodial activity. Here, we describe results from experimental and computational investigations of four structurally related chalcones, butein, 2′,4′-dihydroxy-3,4-dimethoxychalcone (DHDM), homobutein and 5-prenylbutein to elucidate possible molecular mechanisms by which these compounds clear malaria parasites. The crystal structures of butein and DHDM show that butein engages in more hydrogen bonding and consequently, more intermolecular interactions than DHDM. Rotating ring-disk electrode (RRDE) voltammetry results show that butein has a higher antioxidant activity towards the superoxide radical anion compared to DHDM. Computational docking experiments were conducted to examine the inhibitory potential of all four compounds on falcipain-2, a cysteine protease that is involved in the degradation of hemoglobin in plasmodium-infected red blood cells of the host. Overall, this work suggests butein as a better antimalarial compound due to its structural features which allow it to have greater intermolecular interactions, higher antioxidant activity and to create a covalent complex at the active site of falcipain-2.Ijeoma OkoyeSandra YuFrancesco CarusoMiriam RossiMDPI AGarticlefalcipain-2antioxidantchalconebuteinsuperoxideOrganic chemistryQD241-441ENMolecules, Vol 26, Iss 6511, p 6511 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	falcipain-2 antioxidant chalcone butein superoxide Organic chemistry QD241-441
spellingShingle	falcipain-2 antioxidant chalcone butein superoxide Organic chemistry QD241-441 Ijeoma Okoye Sandra Yu Francesco Caruso Miriam Rossi X-ray Structure Determination, Antioxidant Voltammetry Studies of Butein and 2′,4′-Dihydroxy-3,4-dimethoxychalcone. Computational Studies of 4 Structurally Related 2′,4′-diOH Chalcones to Examine Their Antimalarial Activity by Binding to Falcipain-2
description	Malaria is a huge global health burden with resistance to currently available medicines resulting in the search for newer antimalarial compounds from traditional medicinal plants in malaria-endemic regions. Previous studies on two chalcones, homobutein and 5-prenylbutein, present in <i>E. abyssinica</i>, have shown moderate antiplasmodial activity. Here, we describe results from experimental and computational investigations of four structurally related chalcones, butein, 2′,4′-dihydroxy-3,4-dimethoxychalcone (DHDM), homobutein and 5-prenylbutein to elucidate possible molecular mechanisms by which these compounds clear malaria parasites. The crystal structures of butein and DHDM show that butein engages in more hydrogen bonding and consequently, more intermolecular interactions than DHDM. Rotating ring-disk electrode (RRDE) voltammetry results show that butein has a higher antioxidant activity towards the superoxide radical anion compared to DHDM. Computational docking experiments were conducted to examine the inhibitory potential of all four compounds on falcipain-2, a cysteine protease that is involved in the degradation of hemoglobin in plasmodium-infected red blood cells of the host. Overall, this work suggests butein as a better antimalarial compound due to its structural features which allow it to have greater intermolecular interactions, higher antioxidant activity and to create a covalent complex at the active site of falcipain-2.
format	article
author	Ijeoma Okoye Sandra Yu Francesco Caruso Miriam Rossi
author_facet	Ijeoma Okoye Sandra Yu Francesco Caruso Miriam Rossi
author_sort	Ijeoma Okoye
title	X-ray Structure Determination, Antioxidant Voltammetry Studies of Butein and 2′,4′-Dihydroxy-3,4-dimethoxychalcone. Computational Studies of 4 Structurally Related 2′,4′-diOH Chalcones to Examine Their Antimalarial Activity by Binding to Falcipain-2
title_short	X-ray Structure Determination, Antioxidant Voltammetry Studies of Butein and 2′,4′-Dihydroxy-3,4-dimethoxychalcone. Computational Studies of 4 Structurally Related 2′,4′-diOH Chalcones to Examine Their Antimalarial Activity by Binding to Falcipain-2
title_full	X-ray Structure Determination, Antioxidant Voltammetry Studies of Butein and 2′,4′-Dihydroxy-3,4-dimethoxychalcone. Computational Studies of 4 Structurally Related 2′,4′-diOH Chalcones to Examine Their Antimalarial Activity by Binding to Falcipain-2
title_fullStr	X-ray Structure Determination, Antioxidant Voltammetry Studies of Butein and 2′,4′-Dihydroxy-3,4-dimethoxychalcone. Computational Studies of 4 Structurally Related 2′,4′-diOH Chalcones to Examine Their Antimalarial Activity by Binding to Falcipain-2
title_full_unstemmed	X-ray Structure Determination, Antioxidant Voltammetry Studies of Butein and 2′,4′-Dihydroxy-3,4-dimethoxychalcone. Computational Studies of 4 Structurally Related 2′,4′-diOH Chalcones to Examine Their Antimalarial Activity by Binding to Falcipain-2
title_sort	x-ray structure determination, antioxidant voltammetry studies of butein and 2′,4′-dihydroxy-3,4-dimethoxychalcone. computational studies of 4 structurally related 2′,4′-dioh chalcones to examine their antimalarial activity by binding to falcipain-2
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/6b0c5d5b6ee944c68c1e0520bd46d2e8
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X-ray Structure Determination, Antioxidant Voltammetry Studies of Butein and 2′,4′-Dihydroxy-3,4-dimethoxychalcone. Computational Studies of 4 Structurally Related 2′,4′-diOH Chalcones to Examine Their Antimalarial Activity by Binding to Falcipain-2

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