Synthesis and anti-Trypanosoma cruzi activity of β-lapachone analogues

The available chemotherapy for Chagas disease, caused by Trypanosoma cruzi, is unsatisfactory; therefore, there is an intense effort to find new drugs for the treatment of this disease. In our laboratory, we have analyzed the effect on bloodstream trypomastigotes of 16 new naphthoquinone analogues of β-lapachone modified in the pyran ring, aiming to find a new prototype with high trypanocidal activity. The new compounds presented a broad spectrum of activity, and five of them presented IC50/24 h in the range of 22–63 μM, whereas β-lapachone had a higher value of 391.5 ± 16.5 μM.

Sixteen new β-lapachone analogues modified in the pyran ring were assayed against Trypanosoma cruzi trypomastigotes, five of them being 6–17× more active than the original napththoquinone.Figure optionsDownload as PowerPoint slideHighlights
► We analyzed the effect against trypomastigotes of 16 new analogues of β-lapachone.
► We find a new prototype with high trypanocidal activity.
► The compounds presented excellent activity against trypomastigotes
► Such compounds may become more potent and selective trypanocidal drugs