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Antimalarials with Benzothiophene Moieties as Aminoquinoline Partners
Malaria is a severe and life-threatening disease caused by Plasmodium parasites that are spread to humans through bites of infected Anopheles mosquitoes. Here, we report on the efficacy of aminoquinolines coupled to benzothiophene and thiophene rings in inhibiting Plasmodium falciparum parasite grow...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6155332/ https://www.ncbi.nlm.nih.gov/pubmed/28245583 http://dx.doi.org/10.3390/molecules22030343 |
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author | Konstantinović, Jelena Videnović, Milica Srbljanović, Jelena Djurković-Djaković, Olgica Bogojević, Katarina Sciotti, Richard Šolaja, Bogdan |
author_facet | Konstantinović, Jelena Videnović, Milica Srbljanović, Jelena Djurković-Djaković, Olgica Bogojević, Katarina Sciotti, Richard Šolaja, Bogdan |
author_sort | Konstantinović, Jelena |
collection | PubMed |
description | Malaria is a severe and life-threatening disease caused by Plasmodium parasites that are spread to humans through bites of infected Anopheles mosquitoes. Here, we report on the efficacy of aminoquinolines coupled to benzothiophene and thiophene rings in inhibiting Plasmodium falciparum parasite growth. Synthesized compounds were evaluated for their antimalarial activity and toxicity, in vitro and in mice. Benzothiophenes presented in this paper showed improved activities against a chloroquine susceptible (CQS) strain, with potencies of IC(50) = 6 nM, and cured 5/5 Plasmodium berghei infected mice when dosed orally at 160 mg/kg/day × 3 days. In the benzothiophene series, the examined antiplasmodials were more active against the CQS strain D6, than against strains chloroquine resistant (CQR) W2 and multidrug-resistant (MDR) TM91C235. For the thiophene series, a very interesting feature was revealed: hypersensitivity to the CQR strains, resistance index (RI) of <1. This is in sharp contrast to chloroquine, indicating that further development of the series would provide us with more potent antimalarials against CQR strains. |
format | Online Article Text |
id | pubmed-6155332 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-61553322018-11-13 Antimalarials with Benzothiophene Moieties as Aminoquinoline Partners Konstantinović, Jelena Videnović, Milica Srbljanović, Jelena Djurković-Djaković, Olgica Bogojević, Katarina Sciotti, Richard Šolaja, Bogdan Molecules Article Malaria is a severe and life-threatening disease caused by Plasmodium parasites that are spread to humans through bites of infected Anopheles mosquitoes. Here, we report on the efficacy of aminoquinolines coupled to benzothiophene and thiophene rings in inhibiting Plasmodium falciparum parasite growth. Synthesized compounds were evaluated for their antimalarial activity and toxicity, in vitro and in mice. Benzothiophenes presented in this paper showed improved activities against a chloroquine susceptible (CQS) strain, with potencies of IC(50) = 6 nM, and cured 5/5 Plasmodium berghei infected mice when dosed orally at 160 mg/kg/day × 3 days. In the benzothiophene series, the examined antiplasmodials were more active against the CQS strain D6, than against strains chloroquine resistant (CQR) W2 and multidrug-resistant (MDR) TM91C235. For the thiophene series, a very interesting feature was revealed: hypersensitivity to the CQR strains, resistance index (RI) of <1. This is in sharp contrast to chloroquine, indicating that further development of the series would provide us with more potent antimalarials against CQR strains. MDPI 2017-02-24 /pmc/articles/PMC6155332/ /pubmed/28245583 http://dx.doi.org/10.3390/molecules22030343 Text en © 2017 by the authors. 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 (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Konstantinović, Jelena Videnović, Milica Srbljanović, Jelena Djurković-Djaković, Olgica Bogojević, Katarina Sciotti, Richard Šolaja, Bogdan Antimalarials with Benzothiophene Moieties as Aminoquinoline Partners |
title | Antimalarials with Benzothiophene Moieties as Aminoquinoline Partners |
title_full | Antimalarials with Benzothiophene Moieties as Aminoquinoline Partners |
title_fullStr | Antimalarials with Benzothiophene Moieties as Aminoquinoline Partners |
title_full_unstemmed | Antimalarials with Benzothiophene Moieties as Aminoquinoline Partners |
title_short | Antimalarials with Benzothiophene Moieties as Aminoquinoline Partners |
title_sort | antimalarials with benzothiophene moieties as aminoquinoline partners |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6155332/ https://www.ncbi.nlm.nih.gov/pubmed/28245583 http://dx.doi.org/10.3390/molecules22030343 |
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