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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Main Authors: Tatiane Freitas Borgati, Maria Fernanda Alves do Nascimento, Juma Fortunato Bernardino, Lunamaura Claudia Oliveira Martins, Alex Gutterres Taranto, Alaíde Braga de Oliveira
Format: Article
Language:English
Published: Wiley 2017-01-01
Series:Journal of Tropical Medicine
Online Access:http://dx.doi.org/10.1155/2017/7496934
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author Tatiane Freitas Borgati
Maria Fernanda Alves do Nascimento
Juma Fortunato Bernardino
Lunamaura Claudia Oliveira Martins
Alex Gutterres Taranto
Alaíde Braga de Oliveira
author_facet Tatiane Freitas Borgati
Maria Fernanda Alves do Nascimento
Juma Fortunato Bernardino
Lunamaura Claudia Oliveira Martins
Alex Gutterres Taranto
Alaíde Braga de Oliveira
author_sort Tatiane Freitas Borgati
collection DOAJ
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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institution Kabale University
issn 1687-9686
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language English
publishDate 2017-01-01
publisher Wiley
record_format Article
series Journal of Tropical Medicine
spelling doaj-art-e483b30961e94aa49b5b7a4b4e7faa532025-02-03T05:47:03ZengWileyJournal of Tropical Medicine1687-96861687-96942017-01-01201710.1155/2017/74969347496934Synthesis, SAR, and Docking Studies Disclose 2-Arylfuran-1,4-naphthoquinones as In Vitro Antiplasmodial HitsTatiane Freitas Borgati0Maria Fernanda Alves do Nascimento1Juma Fortunato Bernardino2Lunamaura Claudia Oliveira Martins3Alex Gutterres Taranto4Alaíde Braga de Oliveira5Departamento de Produtos Farmacêuticos, Faculdade de Farmácia, UFMG, Campus Pampulha, Av. Antônio Carlos 6627, 31270-901 Belo Horizonte, MG, BrazilDepartamento de Produtos Farmacêuticos, Faculdade de Farmácia, UFMG, Campus Pampulha, Av. Antônio Carlos 6627, 31270-901 Belo Horizonte, MG, BrazilDepartamento de Produtos Farmacêuticos, Faculdade de Farmácia, UFMG, Campus Pampulha, Av. Antônio Carlos 6627, 31270-901 Belo Horizonte, MG, BrazilDepartamento de Produtos Farmacêuticos, Faculdade de Farmácia, UFMG, Campus Pampulha, Av. Antônio Carlos 6627, 31270-901 Belo Horizonte, MG, BrazilFaculdade de Farmácia, UFSJ, Campus Divinópolis, Rua Sebastião Gonçalves Coelho 400, Chanadour, 35501-296 Divinópolis, MG, BrazilDepartamento de Produtos Farmacêuticos, Faculdade de Farmácia, UFMG, Campus Pampulha, Av. Antônio Carlos 6627, 31270-901 Belo Horizonte, MG, BrazilA 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.http://dx.doi.org/10.1155/2017/7496934
spellingShingle Tatiane Freitas Borgati
Maria Fernanda Alves do Nascimento
Juma Fortunato Bernardino
Lunamaura Claudia Oliveira Martins
Alex Gutterres Taranto
Alaíde Braga de Oliveira
Synthesis, SAR, and Docking Studies Disclose 2-Arylfuran-1,4-naphthoquinones as In Vitro Antiplasmodial Hits
Journal of Tropical Medicine
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
url http://dx.doi.org/10.1155/2017/7496934
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