Investigation of thiazolyl-benzothiophenamides as potential agents for African sleeping sickness

  • RSC Med Chem. 2020 Sep 23;11(12):1413-1422. doi: 10.1039/d0md00277a.
Ronald W Brown  1 ,  Ashraf M Abdel-Megeed  1 ,  Paul A Keller  1 ,  Amy J Jones  2 ,  Melissa L Sykes  2 ,  Marcel Kaiser  3  4 ,  Jonathan B Baell  5 ,  Vicky M Avery  2 ,  Christopher J T Hyland  1
Affiliations
  • 1. School of Chemistry and Molecular Bioscience, and Molecular Horizons Research Institute, University of Wollongong Wollongong 2522 NSW Australia [email protected].
  • 2. Discovery Biology, Griffith Institute for Drug Discovery, Griffith University Brisbane Innovation Park Nathan 4111 Australia.
  • 3. Swiss Tropical and Public Health Institute Basel 4051 Switzerland.
  • 4. University of Basel 4003 Basel Switzerland.
  • 5. Medicinal Chemistry, Monash Institute of Pharmaceutical Sciences, Monash University Parkville 3052 Australia.
PMID: 34095848 DOI: 10.1039/d0md00277a
Abstract

African sleeping sickness is a potentially fatal neglected disease affecting sub-Saharan Africa. High-throughput screening identified the thiazolyl-benzothiophenamide 1 to be active against the causative Parasite, Trypanosoma brucei. This work establishes structure-activity relationships of 1, guiding the design of second generation derivatives. After screening against the clinically relevant species T. b. rhodesiense, the derivative 16 was identified as a suitable candidate for further investigation.