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Journal of Tropical Medicine
Volume 2017, Article ID 7496934, 11 pages
https://doi.org/10.1155/2017/7496934
Research Article

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

1Departamento de Produtos Farmacêuticos, Faculdade de Farmácia, UFMG, Campus Pampulha, Av. Antônio Carlos 6627, 31270-901 Belo Horizonte, MG, Brazil
2Faculdade de Farmácia, UFSJ, Campus Divinópolis, Rua Sebastião Gonçalves Coelho 400, Chanadour, 35501-296 Divinópolis, MG, Brazil

Correspondence should be addressed to Alaíde Braga de Oliveira; rb.moc.arret@agarbediala

Received 16 June 2017; Revised 11 August 2017; Accepted 27 August 2017; Published 31 October 2017

Academic Editor: Marcel Tanner

Copyright © 2017 Tatiane Freitas Borgati et al. 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.

Abstract

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.