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Synthesis, SAR, and Docking Studies Disclose 2-Arylfuran-1,4-naphthoquinones as In Vitro Antiplasmodial Hits

A total of 28 lapachol-related naphthoquinones with four different scaffolds were synthesized and spectroscopically characterized. In vitro antiplasmodial activity was assayed against the chloroquine-resistant Plasmodium falciparum W2 strain by the parasite lactate dehydrogenase (pLDH) method. Cytot...

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Autores principales: Borgati, Tatiane Freitas, do Nascimento, Maria Fernanda Alves, Bernardino, Juma Fortunato, Martins, Lunamaura Claudia Oliveira, Taranto, Alex Gutterres, de Oliveira, Alaíde Braga
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Hindawi 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5684547/
https://www.ncbi.nlm.nih.gov/pubmed/29225629
http://dx.doi.org/10.1155/2017/7496934
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author Borgati, Tatiane Freitas
do Nascimento, Maria Fernanda Alves
Bernardino, Juma Fortunato
Martins, Lunamaura Claudia Oliveira
Taranto, Alex Gutterres
de Oliveira, Alaíde Braga
author_facet Borgati, Tatiane Freitas
do Nascimento, Maria Fernanda Alves
Bernardino, Juma Fortunato
Martins, Lunamaura Claudia Oliveira
Taranto, Alex Gutterres
de Oliveira, Alaíde Braga
author_sort Borgati, Tatiane Freitas
collection PubMed
description A total of 28 lapachol-related naphthoquinones with four different scaffolds were synthesized and spectroscopically characterized. In vitro antiplasmodial activity was assayed against the chloroquine-resistant Plasmodium falciparum W2 strain by the parasite lactate dehydrogenase (pLDH) method. Cytotoxicity against Hep G2A16 cell was determined by the MTT assay. All compounds disclosed higher in vitro antiplasmodial activity than lapachol. Ortho- and para-naphthoquinones with a furan ring fused to the quinonoid moiety were more potent than 2-hydroxy-3-(1′-alkenyl)-1,4-naphthoquinones, while ortho-furanonaphthoquinones were more cytotoxic. Molecular docking to Plasmodium targets Pfcyt bc1 complex and PfDHOD enzyme showed that five out of the 28 naphthoquinones disclosed favorable binding energies. Furanonaphthoquinones endowed with an aryl moiety linked to the furan ring are highlighted as new in vitro antiplasmodial lead compounds and warrant further investigation.
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spelling pubmed-56845472017-12-10 Synthesis, SAR, and Docking Studies Disclose 2-Arylfuran-1,4-naphthoquinones as In Vitro Antiplasmodial Hits Borgati, Tatiane Freitas do Nascimento, Maria Fernanda Alves Bernardino, Juma Fortunato Martins, Lunamaura Claudia Oliveira Taranto, Alex Gutterres de Oliveira, Alaíde Braga J Trop Med Research Article A total of 28 lapachol-related naphthoquinones with four different scaffolds were synthesized and spectroscopically characterized. In vitro antiplasmodial activity was assayed against the chloroquine-resistant Plasmodium falciparum W2 strain by the parasite lactate dehydrogenase (pLDH) method. Cytotoxicity against Hep G2A16 cell was determined by the MTT assay. All compounds disclosed higher in vitro antiplasmodial activity than lapachol. Ortho- and para-naphthoquinones with a furan ring fused to the quinonoid moiety were more potent than 2-hydroxy-3-(1′-alkenyl)-1,4-naphthoquinones, while ortho-furanonaphthoquinones were more cytotoxic. Molecular docking to Plasmodium targets Pfcyt bc1 complex and PfDHOD enzyme showed that five out of the 28 naphthoquinones disclosed favorable binding energies. Furanonaphthoquinones endowed with an aryl moiety linked to the furan ring are highlighted as new in vitro antiplasmodial lead compounds and warrant further investigation. Hindawi 2017 2017-10-31 /pmc/articles/PMC5684547/ /pubmed/29225629 http://dx.doi.org/10.1155/2017/7496934 Text en Copyright © 2017 Tatiane Freitas Borgati et al. https://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Borgati, Tatiane Freitas
do Nascimento, Maria Fernanda Alves
Bernardino, Juma Fortunato
Martins, Lunamaura Claudia Oliveira
Taranto, Alex Gutterres
de Oliveira, Alaíde Braga
Synthesis, SAR, and Docking Studies Disclose 2-Arylfuran-1,4-naphthoquinones as In Vitro Antiplasmodial Hits
title Synthesis, SAR, and Docking Studies Disclose 2-Arylfuran-1,4-naphthoquinones as In Vitro Antiplasmodial Hits
title_full Synthesis, SAR, and Docking Studies Disclose 2-Arylfuran-1,4-naphthoquinones as In Vitro Antiplasmodial Hits
title_fullStr Synthesis, SAR, and Docking Studies Disclose 2-Arylfuran-1,4-naphthoquinones as In Vitro Antiplasmodial Hits
title_full_unstemmed Synthesis, SAR, and Docking Studies Disclose 2-Arylfuran-1,4-naphthoquinones as In Vitro Antiplasmodial Hits
title_short Synthesis, SAR, and Docking Studies Disclose 2-Arylfuran-1,4-naphthoquinones as In Vitro Antiplasmodial Hits
title_sort synthesis, sar, and docking studies disclose 2-arylfuran-1,4-naphthoquinones as in vitro antiplasmodial hits
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5684547/
https://www.ncbi.nlm.nih.gov/pubmed/29225629
http://dx.doi.org/10.1155/2017/7496934
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