Discovery of a quinoline-based phenyl sulfone derivative as an antitrypanosomal agent |
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Authors: | Huaisheng Zhang Jasmine Collins Rogers Nyamwihura Shelbi Ware Marcel Kaiser Ifedayo Victor Ogungbe |
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Affiliation: | 1. Department of Chemistry, Jackson State University, Jackson, MS 39217, USA;2. Department of Medical Parasitology & Infection Biology, Swiss Tropical and Public Health Institute, 4051 Basel, Switzerland;3. University of Basel, Petersplatz 1, 4003 Basel, Switzerland |
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Abstract: | A series of natural products-based phenyl sulfone derivative and their property-based analogues were investigated as potential growth inhibitors of Trypanosoma brucei. Trypanosoma brucei is a kinetoplastid protozoan parasite that causes trypanosomiasis. In this work, we found that nopol- and quinoline-based phenyl sulfone derivative were the most active and selective for T. brucei, and they were not reactive towards the active thiol of T. brucei’s cysteine protease rhodesain. A thiol reactive variant of the quinoline-based phenyl sulfone was subsequently investigated and found to be a moderate inhibitor of rhodesain. The quinoline-based compound that is not reactive towards rhodesain can serve a template for phenotypic-based lead discovery while its thiol-active congener can serve as template for structure-based investigation of new antitrypanosomal agents. |
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Keywords: | Cysteine protease Natural products Quinoline |
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