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 Citations (Scopus)

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

Fingerprint

Pentamidine
Trypanosoma cruzi
Toxicity
Nifurtimox
Cells
Drug therapy
Chemotherapy
Chagas Disease
Latin America
Aromatic compounds
Inhibitory Concentration 50
Drug Therapy
In Vitro Techniques
Pharmaceutical Preparations
diguanidine

Keywords

  • Chagas disease
  • Chemotherapy
  • Reversed diamidines
  • Trypanosoma cruzi

ASJC Scopus subject areas

  • Biochemistry
  • Pharmacology

Cite this

Silva, C. F., Batista, M. M., Mota, R. A., de Souza, E. M., Stephens, C. E., Som, P., ... 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

Activity of "reversed" diamidines against Trypanosoma cruzi "in vitro". / Silva, C. F.; Batista, Marcos Meuser; Mota, Renata Alves; de Souza, Elen Mello; Stephens, Chad E.; Som, Phanneth; Boykin, David Wilson; Soeiro, Maria de Nazaré C.

In: Biochemical Pharmacology, Vol. 73, No. 12, 15.06.2007, p. 1939-1946.

Research output: Contribution to journalArticle

Silva, CF, Batista, MM, Mota, RA, de Souza, EM, Stephens, CE, Som, P, Boykin, DW & Soeiro, MDNC 2007, 'Activity of "reversed" diamidines against Trypanosoma cruzi "in vitro"', Biochemical Pharmacology, vol. 73, no. 12, pp. 1939-1946. https://doi.org/10.1016/j.bcp.2007.03.020
Silva, C. F. ; Batista, Marcos Meuser ; Mota, Renata Alves ; de Souza, Elen Mello ; Stephens, Chad E. ; Som, Phanneth ; Boykin, David Wilson ; Soeiro, Maria de Nazaré C. / Activity of "reversed" diamidines against Trypanosoma cruzi "in vitro". In: Biochemical Pharmacology. 2007 ; Vol. 73, No. 12. pp. 1939-1946.
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