Lupeol Acetate and α-Amyrin Terpenes Activity against Trypanosoma cruzi: Insights into Toxicity and Potential Mechanisms of Action

Daniel Pardo-Rodriguez, Andres Cifuentes-López, Juan Bravo-Espejo, Ibeth Romero, Jorge Robles, Claudia Cuervo, Sol M. Mejía, Jair Tellez

Research output: Contribution to journalArticlepeer-review

6 Scopus citations

Abstract

Background: Chagas disease is a potentially fatal disease caused by the parasite Trypanosoma cruzi. There is growing scientific interest in finding new and better therapeutic alternatives for this disease’s treatment. Methods: A total of 81 terpene compounds with potential trypanocidal activity were screened and found to have potential T. cruzi cysteine synthase (TcCS) inhibition using molecular docking, molecular dynamics, ADME and PAIN property analyses and in vitro susceptibility assays. Results: Molecular docking analyses revealed energy ranges from −10.5 to −4.9 kcal/mol in the 81 tested compounds, where pentacyclic triterpenes were the best. Six compounds were selected to assess the stability of the TcCS–ligand complexes, of which lupeol acetate (ACLUPE) and α-amyrin (AMIR) exhibited the highest stability during 200 ns of molecular dynamics analysis. Such stability was primarily due to their hydrophobic interactions with the amino acids located in the enzyme’s active site. In addition, ACLUPE and AMIR exhibited lipophilic characteristics, low intestinal absorption and no structural interferences or toxicity. Finally, selective index for ACLUPE was >5.94, with moderate potency in the trypomastigote stage (EC50 = 15.82 ± 3.7 μg/mL). AMIR’s selective index was >9.36 and it was moderately potent in the amastigote stage (IC50 = 9.08 ± 23.85 μg/mL). Conclusions: The present study proposes a rational approach for exploring lupeol acetate and α-amyrin terpene compounds to design new drugs candidates for Chagas disease.

Original languageEnglish
Article number263
JournalTropical Medicine and Infectious Disease
Volume8
Issue number5
DOIs
StatePublished - May 2023

Keywords

  • Chagas disease
  • Trypanosoma cruzi
  • cysteine synthase
  • docking
  • molecular dynamics
  • terpenes trypanocidal effect

Fingerprint

Dive into the research topics of 'Lupeol Acetate and α-Amyrin Terpenes Activity against Trypanosoma cruzi: Insights into Toxicity and Potential Mechanisms of Action'. Together they form a unique fingerprint.

Cite this