Design, synthesis and antitrypanosomal activities of 2,6-disubstituted-4,5,7-trifluorobenzothiophenes

  • Eur J Med Chem. 2016 Jan 27:108:347-353. doi: 10.1016/j.ejmech.2015.11.043.
Avninder S Bhambra  1 ,  Mark Edgar  2 ,  Mark R J Elsegood  3 ,  Yuqi Li  2 ,  George W Weaver  4 ,  Randolph R J Arroo  5 ,  Vanessa Yardley  6 ,  Hollie Burrell-Saward  6 ,  Vladimir Krystof  7
Affiliations
  • 1. School of Allied Health Sciences, De Montfort University, The Gateway, Leicester, LE1 9BH, UK. Electronic address: [email protected].
  • 2. Department of Chemistry, Loughborough University, Loughborough, LE11 3TU, UK.
  • 3. Department of Chemistry, Loughborough University, Loughborough, LE11 3TU, UK. Electronic address: [email protected].
  • 4. Department of Chemistry, Loughborough University, Loughborough, LE11 3TU, UK. Electronic address: [email protected].
  • 5. Leicester School of Pharmacy, De Montfort University, The Gateway, Leicester, LE1 9BH, UK.
  • 6. London School of Hygiene and Tropical Medicine, London, WC1E 7HT, UK.
  • 7. Palacky University & Institute of Experimental Botany, 11 783 71 Olomouc, Czech Republic.
PMID: 26698538 DOI: 10.1016/j.ejmech.2015.11.043
Abstract

Current treatments for Human African Trypanosomiasis (HAT) are limited in their application, have undesirable dosing regimens and unsatisfactory toxicities highlighting the need for the development of a safer drug pipeline. Our medicinal chemistry programme in developing rapidly accessible and modifiable heterocyclic scaffolds led to the design and synthesis of novel substituted benzothiophenes, with 6-benzimidazol-1-ylbenzothiophene derivatives demonstrating significant antitrypanosomal activities (IC50 < 1 μM) against Trypanosoma brucei rhodesiense and no toxicity towards mammalian cells.

Keywords
Antitrypanosomal activity; Benzothiophenes; Fluorinated drugs; Human African Trypanosomiasis; Sleeping sickness; Trypanosoma brucei rhodesiense.