Antiparasitic Activity of Natural and Semi-Synthetic Tirucallane Triterpenoids from Schinus terebinthifolius (Anacardiaceae): Structure/Activity Relationships

Abstract

Leishmaniasis and Chagas are diseases caused by parasitic protozoans that affect the poorest population in the World, causing a high mortality and morbidity. As a result of highly toxic and long-term treatments, the discovery of novel, safe and more efficacious drugs is essential. In this work, the in vitro antiparasitic activity and mammalian cytotoxicity of three natural tirucallane triterpenoids, isolated from leaves of Schinus terebinthifolius (Anacardiaceae), and nine semi-synthetic derivatives were investigated against Leishmania (L.) infantum and Trypanosoma cruzi. Trypomastigotes of T. cruzi were the most susceptible parasites and seven compounds demonstrated a trypanocidal activity with IC 50 values in the range between 15 and 58 µg/mL. Four compounds demonstrated selectivity towards the intracellular amastigotes of Leishmania, with IC 50 values in the range between 28 and 97 µg/mL. The complete characterization of triterpenoids was afforded after thorough analysis of nuclear magnetic resonance (NMR) data as well as electrospray ionization mass spectrometry (ESI-MS). Additionally, structure-activity relationships were performed using Decision Trees.

Application of an Ionic Liquid in the Microwave Assisted Extraction of Cytotoxic Metabolites from Fruits of Schinus terebinthifolius Raddi (Anacardiaceae)

“…and U87 (21.6 ± 0.7 µg mL -1 ) cells. Similarly to the previous results to antiparasitic activity, 10 the obtained data indicated that the presence of free carboxyl group in the gallic acid is crucial to the cytotoxic potential. However, the use of galloyl derivatives as bioactives must be carefully employed since these compounds could be considered as PAINS (Pan Assay Interference Compounds) since they displayed a catechol unit which can interfere in bioassays via different mechanisms.…”

“…However, the use of galloyl derivatives as bioactives must be carefully employed since these compounds could be considered as PAINS (Pan Assay Interference Compounds) since they displayed a catechol unit which can interfere in bioassays via different mechanisms. 36 Despite the isolated compounds 1, 2, 4 and 5 have already been described for the leaves of S. terebinthifolius, [10][11][12] this study demonstrate, at first time, that it is possible to extract these bioactive compounds using a more sustainably method based in the microwave assisted by ionic liquid. Additionally, this work report the cytotoxic effects of compounds 1-5, highlighting the activity observed for compound 3 which displayed lower IC 50 values of those observed to positive control (cisplatin) to five cell lines.…”

“…[4][5][6][7][8][9][10][11][12] Aiming the extraction of cytotoxic derivatives from fruits of this species, in this work was employed an alternative extraction method based in the use of ionic liquid extraction assisted by microwave. Using this approach, extracting plant material with BMImBr aqueous solution at 3 mol L -1 (experiment 1), followed by partition using EtOAc, were obtained 460 ± 12 mg (yield 23%) of EtOAc fraction.…”

“…As reported in previous papers, [4][5][6][7][8][9][10][11][12] the extraction procedures of bioactive compounds involve the use of toxic organic solvents such as MeOH, acetone, CHCl 3 and hexane in large quantities, leading to a significant environmental impact. The growing interest in adopting more environmentally compatible technologies make these processes inadequate.…”

Mast cell concentration and skin wound contraction in rats treated with Brazilian pepper essential oil (Schinus terebinthifolius Raddi)

“…In popular medicine, it has been used as a treatment for respiratory infections and digestive disorders, such as gastritis, gastric atony and diarrhea. Extracts from BPT have antimicrobial 9,10 , antifungal 11 , antiparasitic 12 and antiinflammatory healing properties 13,14 and aren't toxic to humans 15 . Branco Neto et al 16 refers that the topic use of the hydroalcoholic extract of aroeira delayed the reepitelization of the skin wounds in rats.…”