2. Academic Validation
  3. Discovery of a quinoline-based phenyl sulfone derivative as an antitrypanosomal agent

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

  • Bioorg Med Chem Lett. 2018 May 15;28(9):1647-1651. doi: 10.1016/j.bmcl.2018.03.039.
Huaisheng Zhang 1,  Jasmine Collins 1,  Rogers Nyamwihura 1,  Shelbi Ware 1,  Marcel Kaiser 2,  Ifedayo Victor Ogungbe 3
Affiliations

Affiliations

  • 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; University of Basel, Petersplatz 1, 4003 Basel, Switzerland.
  • 3 Department of Chemistry, Jackson State University, Jackson, MS 39217, USA. Electronic address: ifedayo.v.ogungbe@jsums.edu.
PMID: 29609908 DOI: 10.1016/j.bmcl.2018.03.039
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.

Keywords

Cysteine protease; Natural products; Quinoline; Trypanosoma brucei.

Figures