Discovery of a quinoline-based phenyl sulfone derivative as an antitrypanosomal agent.
- Zhang H Department of Chemistry, Jackson State University, Jackson, MS 39217, USA.
- Collins J Department of Chemistry, Jackson State University, Jackson, MS 39217, USA.
- Nyamwihura R Department of Chemistry, Jackson State University, Jackson, MS 39217, USA.
- Ware S Department of Chemistry, Jackson State University, Jackson, MS 39217, USA.
- Kaiser M Department of Medical Parasitology & Infection Biology, Swiss Tropical and Public Health Institute, 4051 Basel, Switzerland; University of Basel, Petersplatz 1, 4003 Basel, Switzerland.
- Ogungbe IV Department of Chemistry, Jackson State University, Jackson, MS 39217, USA. Electronic address: ifedayo.v.ogungbe@jsums.edu.
- 2018-04-04
Published in:
- Bioorganic & medicinal chemistry letters. - 2018
Cysteine protease
Natural products
Quinoline
Trypanosoma brucei
Biological Products
Dose-Response Relationship, Drug
Drug Discovery
Molecular Structure
Parasitic Sensitivity Tests
Quinolines
Structure-Activity Relationship
Sulfones
Trypanocidal Agents
Trypanosoma brucei brucei
English
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.
- Language
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- English
- Open access status
- green
- Identifiers
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- DOI 10.1016/j.bmcl.2018.03.039
- PMID 29609908
- Persistent URL
- https://folia.unifr.ch/global/documents/246818
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