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Chemotherapy for onchocerciasis: results of in vitro experiments with promising new compounds

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An improved short-term in vitro culture system was used for the routine screening of hundreds of promising new compounds with the target organism, the filarial nematode Onchocerca volvulus. The most active leads were identified among the pyrimidinylguanidines, amidine derivatives, the imidazolinylhydrazones, thiosemicarbazone derivatives and thiadiazole derivatives. Single compounds of these leads demonstrated strong macrofilaricidal efficacy in minimum effective dose trials down to 0.1 mum and in experiments evaluating the minimum time of exposure after less than 6 h exposure. In the group of the pyrimidinylguanidines we found a significant correlation of structure and activity: change of a single side-group in the molecules had dramatic influence on compound activity. Most of the new compounds that were active on the macrofilariae did not show significant activity on microfilariae (mf) in in vitro trials. Only one compound with significant activity against female O. volvulus worms killed mf at very low concentrations. Some of the promising leads will be processed in further trials on a preclinical level with predictive cattle models.
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Keywords: Onchocerca volvulus; in vitro drug assays; macrofilaricidal compounds

Document Type: Research Article

Affiliations: 1: Department of Helminthology and Entomology, Bernhard Nocht Institute for Tropical Medicine, 20359 Hamburg, Germany 2: Onchocerciasis Chemotherapy Research Centre (OCRC), c/o Hohoe Hospital, Hohoe, Ghana

Publication date: 1998-05-01

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