In vitro activity and preliminary toxicity of various diamidine compounds against Trypanosoma evansi

Kirsten Gillingwater, Arvind Kumar, Mohamed A. Ismail, Reem K. Arafa, Chad E. Stephens, David W. Boykin, Richard R. Tidwell, Reto Brun

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

Trypanosoma evansi is an animal pathogenic protozoan, causing a wasting disease called Surra, which is broadly distributed in a wide range of mammalian hosts. Chemotherapy is the most efficient control method, which depends on four drugs. Unfortunately, with the appearance of resistance to these drugs, their effective use is threatened, emphasising a need to find new drugs. Diamidines bind to the minor groove of DNA at AT-rich sites and exert their anti-trypanosomal activity by inhibiting one or more DNA dependent enzymes or by directly impeding the transcription process.In total, 67 novel diamidine compounds were tested in vitro to determine activity against an animal pathogenic Chinese kinetoplastic T. evansi strain. In comparison, a human pathogenic Trypanosoma brucei rhodesiense strain and a P2 transporter knock out of a Trypanosoma brucei brucei strain were also tested. All diamidine compounds tested in this study against T. evansi produced inhibitory concentration (IC50) values below 50nM. The results demonstrate that these compounds are highly active against T. evansi in vitro. In addition, preliminary in vivo toxicity tests were performed on all 67 diamidines with 69% of the compounds showing no acute toxicity at an intra-peritoneal dose of 100mg/kg.

Original languageEnglish (US)
Pages (from-to)264-272
Number of pages9
JournalVeterinary Parasitology
Volume169
Issue number3-4
DOIs
StatePublished - May 1 2010

Fingerprint

Pentamidine
Trypanosoma
Trypanosoma evansi
toxicity
Trypanosoma rhodesiense
surra
Trypanosoma brucei rhodesiense
Trypanosoma brucei brucei
Wasting Syndrome
wasting syndrome
Toxicity Tests
drugs
new drugs
Host Specificity
DNA
acute toxicity
toxicity testing
Drug Resistance
Pharmaceutical Preparations
Inhibitory Concentration 50

Keywords

  • Chemotherapy
  • Diamidines
  • Surra
  • Trypanosoma evansi

ASJC Scopus subject areas

  • Parasitology
  • veterinary(all)

Cite this

In vitro activity and preliminary toxicity of various diamidine compounds against Trypanosoma evansi. / Gillingwater, Kirsten; Kumar, Arvind; Ismail, Mohamed A.; Arafa, Reem K.; Stephens, Chad E.; Boykin, David W.; Tidwell, Richard R.; Brun, Reto.

In: Veterinary Parasitology, Vol. 169, No. 3-4, 01.05.2010, p. 264-272.

Research output: Contribution to journalArticle

Gillingwater, K, Kumar, A, Ismail, MA, Arafa, RK, Stephens, CE, Boykin, DW, Tidwell, RR & Brun, R 2010, 'In vitro activity and preliminary toxicity of various diamidine compounds against Trypanosoma evansi', Veterinary Parasitology, vol. 169, no. 3-4, pp. 264-272. https://doi.org/10.1016/j.vetpar.2010.01.019
Gillingwater, Kirsten ; Kumar, Arvind ; Ismail, Mohamed A. ; Arafa, Reem K. ; Stephens, Chad E. ; Boykin, David W. ; Tidwell, Richard R. ; Brun, Reto. / In vitro activity and preliminary toxicity of various diamidine compounds against Trypanosoma evansi. In: Veterinary Parasitology. 2010 ; Vol. 169, No. 3-4. pp. 264-272.
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