A comparison of the effects of a benzimidazole and the dinitroanilines against Leishmania infantum

A. Armson; S.W. Kamau; F. Grimm; J.A. Reynoldson; W.M. Best; L.M. MacDonald; R.C.A. Thompson

doi:10.1016/S0001-706X(99)00034-0

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A comparison of the effects of a benzimidazole and the dinitroanilines against Leishmania infantum

Journal article

Peer reviewed

A comparison of the effects of a benzimidazole and the dinitroanilines against Leishmania infantum

A. Armson, S.W. Kamau, F. Grimm, J.A. Reynoldson, W.M. Best, L.M. MacDonald and R.C.A. Thompson

Acta Tropica, Vol.73(3), pp.303-311

1999

DOI: https://doi.org/10.1016/S0001-706X(99)00034-0

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Abstract

Leishmania infantum promastigotes and amastigotes were axenically cultured and exposed to the known tubulin binding compounds, the dinitroanilines, trifluralin, benfluralin, pendimethalin, oryzalin and the precursor of the dinitroanilines, chloralin, as well as isomers of chloralin and trifluralin and to the benzimidazole, albendazole. Drug induced inhibition was observed using [3H]thymidine uptake compared with untreated controls. In vitro analysis demonstrated a significant difference in the activity of five of the seven dinitroanilines between both life cycle stages of L. infantum. The amastigotes were 20-times more sensitive to chloralin and its isomer than to the dinitroanilines whereas the promastigotes were similar in sensitivity to the dinitroanilines and to chloralin and its isomer. This interesting finding suggests that the dinitroaniline precursors may have different target sites in the amastigotes to those within the promastigotes. Additionally, both chloralin and its isomer, and to a lesser extent benfluralin, caused a substantial stimulation of thymidine incorporation (up to 50%) at low concentrations. Dose response analysis suggests that the dinitroanilines may have more than one mode of action against L. infantum amastigotes and promastigotes. The inhibitory effects of the dinitroanilines against L. infantum vary from previous findings using the dinitroanilines against other Leishmania spp. The 348 base pair DNA sequence coding for β- tubulin from amino acid residues 132 to 248 was obtained for L. infantum and used to compare the in vivo efficacy of albendazole with predicted activity based on β-tubulin sequences of known benzimidazole sensitive protozoa. The use of β-tubulin sequence as a predictive model of benzimidazole activity is discussed with particular reference to L. infantum.

Details

Title: A comparison of the effects of a benzimidazole and the dinitroanilines against Leishmania infantum
Authors/Creators: A. Armson (Author/Creator) - Murdoch University
S.W. Kamau (Author/Creator) - University of Zurich
F. Grimm (Author/Creator) - University of Zurich
J.A. Reynoldson (Author/Creator) - Murdoch University
W.M. Best (Author/Creator) - ChemCentre
L.M. MacDonald (Author/Creator) - Murdoch University
R.C.A. Thompson (Author/Creator)
Publication Details: Acta Tropica, Vol.73(3), pp.303-311
Publisher: Elsevier BV
Identifiers: 991005543718407891
Murdoch Affiliation: School of Veterinary and Biomedical Sciences
Language: English
Resource Type: Journal article

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Collaboration types: Domestic collaboration; International collaboration
Citation topics: 1 Clinical & Life Sciences; 1.261 Parasitology - Trypanosoma & Leishmania; 1.261.695 Leishmaniasis Dynamics
Web Of Science research areas: Parasitology; Tropical Medicine
ESI research areas: Clinical Medicine