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

• Published in: Journal of Tropical Medicine
• 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 in Journal/Newspaper
• Language: English
• Published: Hindawi Limited 2017
• Subjects: Arctic medicine. Tropical medicine; RC955-962; Arctic
• Online Access: https://doi.org/10.1155/2017/7496934; https://doaj.org/article/e483b30961e94aa49b5b7a4b4e7faa53

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.