Trypanosoma cruzi is the agent of Chagas disease, an infection that affects around 8 million people worldwide. The search for new anti-T. cruzi drugs are relevant, mainly because the treatment of this disease is limited to two drugs. The objective of this study was to investigate the trypanocidal and cytotoxic activity and elucidate the chemical profile of extracts from the roots of the Lonchocarpus cultratus. Roots from L. cultratus were submitted to successive extractions with hexane, dichloromethane, and methanol, resulting in LCH, LCD, and LCM extracts, respectively. Characterization of extracts was done using 1H-RMN, 13C-RMN, CC and TLC. Treatment of T. cruzi forms (epimastigotes, trypomastigotes, and amastigotes) with crescent concentrations of LCH, LCD, and LCM was done for 72, 48, and 48 h, respectively. After this, the percentage of inhibition and IC50/LC50 were calculated. Benznidazole was used as a positive control. Murine macrophages were treated with different concentrations of both extracts for 48 h, and after, the cellular viability was determined by the MTT method and CC50 was calculated. The chalcones derricin and lonchocarpine were identified in the hexane extract, and for the first time in the genus Lonchocarpus, the presence of a dihydrolonchocarpine derivative was observed. Other chalcones such as isocordoin and erioschalcone B were detected in the dichloromethane extract. The dichloromethane extract showed higher activity against all tested forms of T. cruzi than the other two extracts, with IC50 values of 10.98, 2.42, and 0.83 µg/mL, respectively; these values are very close to those of benznidazole. Although the dichloromethane extract presented a cytotoxic effect against mammalian cells, it showed selectivity against amastigotes. The methanolic extract showed the lowest anti-T. cruzi activity but was non-toxic to peritoneal murine macrophages. Thus, the genus Lonchocarpus had demonstrated in the past action against epimastigotes forms of T. cruzi but is the first time that the activity against infective forms is showed, which leading to further studies with in vivo tests.
Keywords: ANOVA, Analysis of Variance; BZN, Benznidazole; CC, column chromatography; CC50, Cytotoxic Concentration 50%; CDCl3, Deuterate chloroform; CO2, Carbon dioxide; Chagas disease; Chalcones; DC, DMSO Control; DMSO, Dimethyl Sulfoxide; FBS, Fetal Bovine Serum; IC50, Inhibitory Concentration 50%; LC-1, 2 and 3: Fractions obtained from LCH extract; LC-4 and 5, fractions obtained from LCD extract; LC50, Lethal Concentration 50%; LCD, Extract from L. cultratus obtained by extraction with dichloromethane; LCH, Extract from L. cultratus obtained by extraction with hexane; LCM, Extract from L. cultratus obtained by extraction with methanol; LIT, Liver Infusion Tryptose; Lafepe, Pharmaceutical Laboratory of Pernambuco State; Lonchocarpus; MTT, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide; NMR, Nuclear Magnetic Resonance; NO, Nitric Oxide; PBS, Phosphate-Buffered Saline; Plant extract; RPMI, Roswell Park Memorial Institute; SI, Selectivity Index; TLC, Thin Layer column; TMS, Tetramethylsilane; Trypanosomiasis; UC, Untreated Control; UEM, State University of Maringa/PR.
© 2020 The Authors.