Synthesis of (-) - 6,6'-dinitrohinokinin from hinokinin natural product and in silico and in vitro trypanocidal activity assessment

Abstract

Chagas disease is a public health problem affecting approximately seven million people worldwide. Thus, there is a need to discover drugs for the adequate treatment of this disease because currently available drugs have serious side effects. Therefore, this study aimed to evaluate the in vitro trypanocidal activity of (-)-6,6'-dinitrohinokinin, obtained from the partial synthesis of (-)-hinokinin, on the trypomastigotes and amastigotes forms. For the trypomastigote assay, blood was collected from mice infected with Trypanosoma cruzi through cardiac puncture at the parasitemic peak. The results show that (-)-6,6'-dinitrohinokinin was effective against the trypomastigote forms, presenting an IC50 of 19.83 µM and lysis percentage values ​​of 78.4% and 69.4% at concentrations of 200 and 100 µM, respectively. Molecular docking calculations indicate that (-)-6,6'-dinitrohinokinin favorably interacts with the amino acids present in the active site of the protein trypanothione reductase, a typical target for anti-trypanosomal drug development. According to the results, the (-)-6,6'-dinitrohinokinin showed more significant trypanocidal activity with IC50 of 1.83 µM than benzonidazole positive control with IC50 of 53.2 µM, showing to be a prototype molecule promising for the development of a new antiparasitic drug.