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Discovery of a quinoline-based phenyl sulfone derivative as an antitrypanosomal agent.

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.

SUBMITTER: Zhang H

PROVIDER: S-EPMC5912169 | biostudies-literature | 2018 May

REPOSITORIES: biostudies-literature

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Discovery of a quinoline-based phenyl sulfone derivative as an antitrypanosomal agent.

Zhang Huaisheng H Collins Jasmine J Nyamwihura Rogers R Ware Shelbi S Kaiser Marcel M Ogungbe Ifedayo Victor IV

Bioorganic & medicinal chemistry letters 20180324 9

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 va ...[more]

PMID: 29609908

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