Abstract
A potent filaricidal effect of bis(benzyl)polyamine derivatives is reported; the addition of 1 μM MDL 27695 toBrugia pahangi maintained in vitro killed the worms within 1 week. Using the labelled derivative, MDL 27391 uptake was demonstrated and evidence was provided for an uptake system that is independent of and clearly distinguishable from those for polyamines. TheK m value for the uptake of MDL 27391 was determined to be 2 μM, and that for putrescine, spermidine, and spermine was 4.9, 1.7, and 4.8 μM, respectively. The uptake of MDL 27391 was not affected by polyamines. In contrast, bis(benzyl)polyamines were shown to be strong inhibitors of both the putrescine and the spermidine/spermine uptake system. As shown for MDL 27391, bis(benzyl)polyamines are not metabolized after uptake byBrugia worms; therefore, it is expected that the filaricidal effect of the drug depends on its interaction with potential polyamine-binding sites.
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Müller, S., Lüchow, A., McCann, P.P. et al. Effect of bis(benzyl)polyamine derivatives on polyamine transport and survival ofBrugia pahangi . Parasitol Res 77, 612–615 (1991). https://doi.org/10.1007/BF00931024
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DOI: https://doi.org/10.1007/BF00931024