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.

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