On the search for potential anti-Trypanosoma cruzi drugs: Synthesis and biological evaluation of 2-hydroxy-3-methylamino and 1,2,3-triazolic naphthoquinoidal compounds obtained by click chemistry reactions

Five 2-hydroxy-3-substituted-aminomethyl naphthoquinones, nine 1,2,3-triazolic para-naphthoquinones, five nor-β-lapachone-based 1,2,3-triazoles, and several other naphthoquinonoid compounds were synthesized and evaluated against the infective bloodstream form of Trypanosoma cruzi, the etiological agent of Chagas disease, continuing our screening program for new trypanocidal compounds. Among all the substances, 16–18, 23, 25–29 and 30–33 were herein described for the first time and fifteen substances were identified as more potent than the standard drug benznidazole, with IC50/24 h values in the range of 10.9–101.5 μM. Compounds 14 and 19 with Selectivity Index of 18.9 and 6.1 are important structures for further studies.

Graphical abstractFigure optionsDownload full-size imageDownload as PowerPoint slideHighlights► Naphthoquinones-based 1,2,3-triazoles were obtained with trypanocidal activity. ► Quinonoid compounds against the infective bloodstream form of Trypanosoma cruzi were developed. ► Fifteen substances were more active than the anti-T. cruzi drug benznidazole. ► Fifteen compounds were described with IC50/24 h values in the range of 10.9–101.5 μM.