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Synthesis and Evaluation of Chalcone-Quinoline Based Molecular Hybrids as Potential Anti-Malarial Agents

Molecular hybridization is a drug discovery strategy that involves the rational design of new chemical entities by the fusion (usually via a covalent linker) of two or more drugs, both active compounds and/or pharmacophoric units recognized and derived from known bioactive molecules. The expected ou...

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Detalles Bibliográficos
Autores principales: Vinindwa, Bonani, Dziwornu, Godwin Akpeko, Masamba, Wayiza
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8272121/
https://www.ncbi.nlm.nih.gov/pubmed/34279438
http://dx.doi.org/10.3390/molecules26134093
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author Vinindwa, Bonani
Dziwornu, Godwin Akpeko
Masamba, Wayiza
author_facet Vinindwa, Bonani
Dziwornu, Godwin Akpeko
Masamba, Wayiza
author_sort Vinindwa, Bonani
collection PubMed
description Molecular hybridization is a drug discovery strategy that involves the rational design of new chemical entities by the fusion (usually via a covalent linker) of two or more drugs, both active compounds and/or pharmacophoric units recognized and derived from known bioactive molecules. The expected outcome of this chemical modification is to produce a new hybrid compound with improved affinity and efficacy compared to the parent drugs. Additionally, this strategy can result in compounds presenting modified selectivity profiles, different and/or dual modes of action, reduced undesired side effects and ultimately lead to new therapies. In this study, molecular hybridization was used to generate new molecular hybrids which were tested against the chloroquine sensitive (NF54) strain of P. falciparum. To prepare the new molecular hybrids, the quinoline nucleus, one of the privileged scaffolds, was coupled with various chalcone derivatives via an appropriate linker to produce a total of twenty-two molecular hybrids in 11%–96% yield. The synthesized compounds displayed good antiplasmodial activity with IC(50) values ranging at 0.10–4.45 μM.
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spelling pubmed-82721212021-07-11 Synthesis and Evaluation of Chalcone-Quinoline Based Molecular Hybrids as Potential Anti-Malarial Agents Vinindwa, Bonani Dziwornu, Godwin Akpeko Masamba, Wayiza Molecules Article Molecular hybridization is a drug discovery strategy that involves the rational design of new chemical entities by the fusion (usually via a covalent linker) of two or more drugs, both active compounds and/or pharmacophoric units recognized and derived from known bioactive molecules. The expected outcome of this chemical modification is to produce a new hybrid compound with improved affinity and efficacy compared to the parent drugs. Additionally, this strategy can result in compounds presenting modified selectivity profiles, different and/or dual modes of action, reduced undesired side effects and ultimately lead to new therapies. In this study, molecular hybridization was used to generate new molecular hybrids which were tested against the chloroquine sensitive (NF54) strain of P. falciparum. To prepare the new molecular hybrids, the quinoline nucleus, one of the privileged scaffolds, was coupled with various chalcone derivatives via an appropriate linker to produce a total of twenty-two molecular hybrids in 11%–96% yield. The synthesized compounds displayed good antiplasmodial activity with IC(50) values ranging at 0.10–4.45 μM. MDPI 2021-07-05 /pmc/articles/PMC8272121/ /pubmed/34279438 http://dx.doi.org/10.3390/molecules26134093 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
Vinindwa, Bonani
Dziwornu, Godwin Akpeko
Masamba, Wayiza
Synthesis and Evaluation of Chalcone-Quinoline Based Molecular Hybrids as Potential Anti-Malarial Agents
title Synthesis and Evaluation of Chalcone-Quinoline Based Molecular Hybrids as Potential Anti-Malarial Agents
title_full Synthesis and Evaluation of Chalcone-Quinoline Based Molecular Hybrids as Potential Anti-Malarial Agents
title_fullStr Synthesis and Evaluation of Chalcone-Quinoline Based Molecular Hybrids as Potential Anti-Malarial Agents
title_full_unstemmed Synthesis and Evaluation of Chalcone-Quinoline Based Molecular Hybrids as Potential Anti-Malarial Agents
title_short Synthesis and Evaluation of Chalcone-Quinoline Based Molecular Hybrids as Potential Anti-Malarial Agents
title_sort synthesis and evaluation of chalcone-quinoline based molecular hybrids as potential anti-malarial agents
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8272121/
https://www.ncbi.nlm.nih.gov/pubmed/34279438
http://dx.doi.org/10.3390/molecules26134093
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