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Anti-malarial effect of novel chloroquine derivatives as agents for the treatment of malaria

BACKGROUND: The widespread emergence of anti-malarial drug resistance has necessitated the discovery of novel anti-malarial drug candidates. In this study, chloroquine derivatives were evaluated for the improved anti-malarial activity. RESULTS: Novel two derivatives (SKM13 and SKM14) were synthesize...

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Autores principales: Yeo, Seon-Ju, Liu, Dong-Xu, Kim, Hak Sung, Park, Hyun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5316213/
https://www.ncbi.nlm.nih.gov/pubmed/28212631
http://dx.doi.org/10.1186/s12936-017-1725-z
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author Yeo, Seon-Ju
Liu, Dong-Xu
Kim, Hak Sung
Park, Hyun
author_facet Yeo, Seon-Ju
Liu, Dong-Xu
Kim, Hak Sung
Park, Hyun
author_sort Yeo, Seon-Ju
collection PubMed
description BACKGROUND: The widespread emergence of anti-malarial drug resistance has necessitated the discovery of novel anti-malarial drug candidates. In this study, chloroquine derivatives were evaluated for the improved anti-malarial activity. RESULTS: Novel two derivatives (SKM13 and SKM14) were synthesized based on the chloroquine (CQ) template containing modified side chains such as α,β-unsaturated amides and phenylmethyl group. The selective index indicated that SKM13 was 1.28-fold more effective than CQ against the CQ-resistant strain Plasmodium falciparum. An in vivo mouse study demonstrated that SKM13 (20 mg/kg) could completely inhibit Plasmodium berghei growth in blood and increased the survival rate from 40 to 100% at 12 days after infection. Haematological parameters [red blood cell (RBC) count, haemoglobin level, and haematocrit level] were observed as an indication of clinical malarial anaemia during an evaluation of the efficacy of SKM13 in a 4-day suppression test. An in vivo study showed a decrease of greater than 70% in the number of RBC in P. berghei-infected mice over 12 days, but the SKM13 (20 mg/kg)-treated group showed no loss of RBC. CONCLUSIONS: CQ derivatives with substituents such as α,β-unsaturated amides and phenylmethyl group have enhanced anti-malarial activity against the CQ-resistant strain P. falciparum, and SKM13 is an excellent anti-malarial drug candidate in mice model. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12936-017-1725-z) contains supplementary material, which is available to authorized users.
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spelling pubmed-53162132017-02-24 Anti-malarial effect of novel chloroquine derivatives as agents for the treatment of malaria Yeo, Seon-Ju Liu, Dong-Xu Kim, Hak Sung Park, Hyun Malar J Research BACKGROUND: The widespread emergence of anti-malarial drug resistance has necessitated the discovery of novel anti-malarial drug candidates. In this study, chloroquine derivatives were evaluated for the improved anti-malarial activity. RESULTS: Novel two derivatives (SKM13 and SKM14) were synthesized based on the chloroquine (CQ) template containing modified side chains such as α,β-unsaturated amides and phenylmethyl group. The selective index indicated that SKM13 was 1.28-fold more effective than CQ against the CQ-resistant strain Plasmodium falciparum. An in vivo mouse study demonstrated that SKM13 (20 mg/kg) could completely inhibit Plasmodium berghei growth in blood and increased the survival rate from 40 to 100% at 12 days after infection. Haematological parameters [red blood cell (RBC) count, haemoglobin level, and haematocrit level] were observed as an indication of clinical malarial anaemia during an evaluation of the efficacy of SKM13 in a 4-day suppression test. An in vivo study showed a decrease of greater than 70% in the number of RBC in P. berghei-infected mice over 12 days, but the SKM13 (20 mg/kg)-treated group showed no loss of RBC. CONCLUSIONS: CQ derivatives with substituents such as α,β-unsaturated amides and phenylmethyl group have enhanced anti-malarial activity against the CQ-resistant strain P. falciparum, and SKM13 is an excellent anti-malarial drug candidate in mice model. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12936-017-1725-z) contains supplementary material, which is available to authorized users. BioMed Central 2017-02-17 /pmc/articles/PMC5316213/ /pubmed/28212631 http://dx.doi.org/10.1186/s12936-017-1725-z Text en © The Author(s) 2017 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research
Yeo, Seon-Ju
Liu, Dong-Xu
Kim, Hak Sung
Park, Hyun
Anti-malarial effect of novel chloroquine derivatives as agents for the treatment of malaria
title Anti-malarial effect of novel chloroquine derivatives as agents for the treatment of malaria
title_full Anti-malarial effect of novel chloroquine derivatives as agents for the treatment of malaria
title_fullStr Anti-malarial effect of novel chloroquine derivatives as agents for the treatment of malaria
title_full_unstemmed Anti-malarial effect of novel chloroquine derivatives as agents for the treatment of malaria
title_short Anti-malarial effect of novel chloroquine derivatives as agents for the treatment of malaria
title_sort anti-malarial effect of novel chloroquine derivatives as agents for the treatment of malaria
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5316213/
https://www.ncbi.nlm.nih.gov/pubmed/28212631
http://dx.doi.org/10.1186/s12936-017-1725-z
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