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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
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 E. abyssinica, h...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8588236/ https://www.ncbi.nlm.nih.gov/pubmed/34770920 http://dx.doi.org/10.3390/molecules26216511 |
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author | Okoye, Ijeoma Yu, Sandra Caruso, Francesco Rossi, Miriam |
author_facet | Okoye, Ijeoma Yu, Sandra Caruso, Francesco Rossi, Miriam |
author_sort | Okoye, Ijeoma |
collection | PubMed |
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 E. abyssinica, 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 | Online Article Text |
id | pubmed-8588236 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-85882362021-11-13 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 Okoye, Ijeoma Yu, Sandra Caruso, Francesco Rossi, Miriam Molecules Article 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 E. abyssinica, 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. MDPI 2021-10-28 /pmc/articles/PMC8588236/ /pubmed/34770920 http://dx.doi.org/10.3390/molecules26216511 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Okoye, Ijeoma Yu, Sandra Caruso, Francesco Rossi, Miriam 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 | 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_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_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 |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8588236/ https://www.ncbi.nlm.nih.gov/pubmed/34770920 http://dx.doi.org/10.3390/molecules26216511 |
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