title: Design, synthesis and antitrypanosomal activities of 2,6-disubstituted-4,5,7-trifluorobenzothiophenes.
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.
authors.affiliation: School of Allied Health Sciences, De Montfort University, The Gateway, Leicester, LE1 9BH, UK. Electronic address: abhambra@dmu.ac.uk.
authors.forename: Avninder S
authors.initials: AS
authors.lastname: Bhambra
authors.affiliation: Department of Chemistry, Loughborough University, Loughborough, LE11 3TU, UK.
authors.forename: Mark
authors.initials: M
authors.lastname: Edgar
authors.affiliation: Department of Chemistry, Loughborough University, Loughborough, LE11 3TU, UK. Electronic address: m.r.j.elsegood@lboro.ac.uk.
authors.forename: Mark R J
authors.initials: MRJ
authors.lastname: Elsegood
authors.affiliation: Department of Chemistry, Loughborough University, Loughborough, LE11 3TU, UK.
authors.forename: Yuqi
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Chemistry, Loughborough University, Loughborough, LE11 3TU, UK. Electronic address: g.w.weaver@lboro.ac.uk.
authors.forename: George W
authors.initials: GW
authors.lastname: Weaver
authors.affiliation: Leicester School of Pharmacy, De Montfort University, The Gateway, Leicester, LE1 9BH, UK.
authors.forename: Randolph R J
authors.initials: RRJ
authors.lastname: Arroo
authors.affiliation: London School of Hygiene and Tropical Medicine, London, WC1E 7HT, UK.
authors.forename: Vanessa
authors.initials: V
authors.lastname: Yardley
authors.affiliation: London School of Hygiene and Tropical Medicine, London, WC1E 7HT, UK.
authors.forename: Hollie
authors.initials: H
authors.lastname: Burrell-Saward
authors.affiliation: Palacky University & Institute of Experimental Botany, 11 783 71 Olomouc, Czech Republic.
authors.forename: Vladimir
authors.initials: V
authors.lastname: Krystof
mesh_terms: D000981:Antiprotozoal Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D008958:Models, Molecular; D015394:Molecular Structure; D021261:Parasitic Sensitivity Tests; D013329:Structure-Activity Relationship; D013876:Thiophenes / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D016833:Trypanosoma brucei rhodesiense / Q000187:drug effects*
chemical_list: D000981:Antiprotozoal Agents; D013876:Thiophenes
keywords: Antitrypanosomal activity; Benzothiophenes; Fluorinated drugs; Human African Trypanosomiasis; Sleeping sickness; Trypanosoma brucei rhodesiense