Activity of "reversed" diamidines against Trypanosoma cruzi "in vitro"

C. F. Silva, Marcos Meuser Batista, Renata Alves Mota, Elen Mello de Souza, Chad E. Stephens, Phanneth Som, David Wilson Boykin, Maria de Nazaré C. Soeiro

Research output: Contribution to journalArticle

48 Scopus citations

Abstract

Chagas' disease is an important parasitic illness caused by the flagellated protozoan Trypanosoma cruzi. The disease affects nearly 17 million individuals in endemic areas of Latin America and the current chemotherapy is quite unsatisfactory based on nitroheterocyclic agents (nifurtimox and benznidazol). The need for new compounds with different modes of action is clear. Due to the broad-spectrum antimicrobial activity of the aromatic dicationic compounds, this study focused on the activity of four such diamidines (DB811, DB889, DB786, DB702) and a closely related diguanidine (DB711) against bloodstream trypomastigotes as well as intracellular amastigotes of T. cruzi in vitro. Additional studies were also conducted to access the toxicity of the compounds against mammalian cells in vitro. Our data show that the four diamidines compounds presented early and high anti-parasitic activity (IC50 in low-micromolecular range) exhibiting trypanocidal dose-dependent effects against both trypomastigote and amastigote forms of T. cruzi 2 h after drug treatment. Most of the diamidines compounds (except the DB702) exerted high anti-parasitic activity and low toxicity to the mammalian cells. Our results show the activity of reversed diamidines against T. cruzi and suggested that the compounds merit in vivo studies.

Original languageEnglish (US)
Pages (from-to)1939-1946
Number of pages8
JournalBiochemical Pharmacology
Volume73
Issue number12
DOIs
StatePublished - Jun 15 2007
Externally publishedYes

Keywords

  • Chagas disease
  • Chemotherapy
  • Reversed diamidines
  • Trypanosoma cruzi

ASJC Scopus subject areas

  • Biochemistry
  • Pharmacology

Fingerprint Dive into the research topics of 'Activity of "reversed" diamidines against Trypanosoma cruzi "in vitro"'. Together they form a unique fingerprint.

  • Cite this

    Silva, C. F., Batista, M. M., Mota, R. A., de Souza, E. M., Stephens, C. E., Som, P., Boykin, D. W., & Soeiro, M. D. N. C. (2007). Activity of "reversed" diamidines against Trypanosoma cruzi "in vitro". Biochemical Pharmacology, 73(12), 1939-1946. https://doi.org/10.1016/j.bcp.2007.03.020