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: | , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2017-01-01
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| 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. |
| format | Article |
| id | doaj-art-e483b30961e94aa49b5b7a4b4e7faa53 |
| institution | Kabale University |
| issn | 1687-9686 1687-9694 |
| 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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