Lignans Isolated from Piper truncatum Act as New Potent Antitrypanosomal Compounds

Chem Biodivers. 2024 May;21(5):e202400547. doi: 10.1002/cbdv.202400547. Epub 2024 Apr 12.

Abstract

The hexane extract from twigs of Piper truncatum Vell (Piperaceae) displayed activity against Trypanosoma cruzi and was subjected to chromatographic steps to afford six dibenzylbutyrolactolic lignans, being four knowns: cubebin (1), (-)-9α-O-methylcubebin (2), (+)-9β-O-methylcubebinin (3) and 3,4-dimethoxy-3,4-demethylenedioxycubebin (4) as well as two new, named truncatin A (5) and B (6). Initially, in vitro activity against trypomastigotes was evaluated and compounds 1, 4 and 6 exhibited EC50 values of 41.6, 21.0 and 39.6 μM, respectively. However, when tested against amastigotes, the relevant clinical form in the chronic phase of Chagas disease, compounds 1-6 displayed activities with EC50 values ranging from 1.6 to 13.7 μM. In addition, the mammalian cytotoxicity of compounds 1-6 was evaluated against murine fibroblasts (NCTC). Compounds 2, 3 and 4 exhibited reduced toxicity against NCTC cells (CC50>200 μM), resulting in SI values of>21.9,>14.5 and>121.9, respectively. Compound 4 showed the highest potency with an SI value twice superior to that determined by the standard drug benznidazole (SI>54.6) against the intracellular amastigotes. These data suggest that lignan 4 can be considered a possible scaffold for designing a new drug candidate for Chagas disease.

Keywords: Piper truncatum Vell; Trypanosoma cruzi; lignans.

MeSH terms

  • Animals
  • Cell Survival / drug effects
  • Dose-Response Relationship, Drug
  • Fibroblasts / drug effects
  • Lignans* / chemistry
  • Lignans* / isolation & purification
  • Lignans* / pharmacology
  • Mice
  • Molecular Structure
  • Parasitic Sensitivity Tests
  • Piper* / chemistry
  • Plant Extracts / chemistry
  • Plant Extracts / isolation & purification
  • Plant Extracts / pharmacology
  • Structure-Activity Relationship
  • Trypanocidal Agents* / chemistry
  • Trypanocidal Agents* / isolation & purification
  • Trypanocidal Agents* / pharmacology
  • Trypanosoma cruzi* / drug effects