Abstract
Chagas disease infects approximately seven million people worldwide. Benznidazole is effective only in the acute phase of the disease, with an average cure rate of 80% between acute and recent cases. Therefore, there is an urgent need to find new bioactive substances that can be effective against parasites without causing so many complications to the host. In this study, the triterpene 3β-6β-16β-trihydroxilup-20 (29)-ene (CLF-1) was isolated from Combretum leprosum, and its molecular structure was determined by NMR and infrared spectroscopy. The CLF-1 was also evaluated in vitro and in silico as potential trypanocidal agent against epimastigote and trypomastigote forms of Trypanosoma cruzi (Y strain). The CLF-1 demonstrated good results highlighted by lower IC50 (76.0 ± 8.72 µM, 75.1 ± 11.0 µM, and 70.3 ± 45.4 µM) for epimastigotes at 24, 48 and 72 h, and LC50 (71.6 ± 11.6 µM) for trypomastigotes forms. The molecular docking study shows that the CLF-1 was able to interact with important TcGAPDH residues, suggesting that this natural compound may preferentially exert its effect by compromising the glycolytic pathway in T. cruzi. The ADMET study together with the MTT results indicated that the CLF-1 is well-absorbed in the intestine and has low toxicity. Thus, this work adds new evidence that CLF-1 can potentially be used as a candidate for the development of new options for the treatment of Chagas disease.
Communicated by Ramaswamy H. Sarma
Acknowledgements
We thank the financial support from CNPq, CAPES, and FUNCAP. Francisco Wagner Q. Almeida-Neto thanks CNPq for his grant. Pedro de Lima-Neto thanks for the financial support received from the CNPq project: 304152/2018-8. Alice Maria Costa Martins thanks the financial support received from the CNPq project: 3066142019-7. Hélcio Silva dos Santos acknowledges financial support from the PQ/BPI-FUNCAP (Grant BP4-0172-00075.01.00/20), Alexandre Magno Rodrigues Teixeira acknowledges financial support from CNPq (Grant 305719/2018-1). The authors also thank Centro Nacional de Processamento de Alto Desempenho (CENAPAD) of the Federal University of Ceará (UFC) for providing computational resources.
Disclosure statement
No potential conflict of interest was reported by the authors.