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Classical Ligands Bind Tubulin of Trypanosomes and Inhibit Their Growth In vitro

Donasian O. K. Ochola, Roger K. Prichard and George W. Lubega
The Journal of Parasitology
Vol. 88, No. 3 (Jun., 2002), pp. 600-604
DOI: 10.2307/3285457
Stable URL: http://www.jstor.org/stable/3285457
Page Count: 5
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Since scans are not currently available to screen readers, please contact JSTOR User Support for access. We'll provide a PDF copy for your screen reader.
Classical Ligands Bind Tubulin of Trypanosomes and Inhibit Their Growth In vitro
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Abstract

Tubulin ligands known to be toxic to certain organisms or cells were tested for their ability to inhibit proliferation of trypanosomes in culture. Tubulin was purified from Trypanosoma brucei or rat brain by poly-L-lysine affinity chromatography and used in binding studies in order to compare the binding of [3H]mebendazole to trypanosome and mammalian tubulin. All the compounds tested in culture inhibited trypanosome proliferation in a concentration-dependent manner. The concentration required to inhibit trypanosome proliferation by 50 or 90% (IC50 or IC90) in 24 hr was determined for each compound. There were no significant differences (P > 0.05) among the benzimidazoles (BZs), but colchicine and vinblastine caused significantly greater inhibitions than the Bzs (P < 0.02 and P < 0.005, respectively). Increasing the incubation time to 72 hr caused a 2- to 4-fold lowering of the IC50 and IC90 values for all the drugs. In the binding assays, there was higher total binding of [3H]mebendazole to trypanosome than rat brain tubulin. The results suggest that the inhibition of trypanosome growth was caused by the specific interaction of these ligands with trypanosome tubulin. Trypanosome tubulin is, therefore, a reasonable target against which novel drugs can be developed to control trypanosomiasis.

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