title: Evaluation of the anti-trypanosomal activity of tyropeptin A.
abstract: The natural compound tyropeptin A, a new peptidyl aldehyde proteasome inhibitor, was tested for its trypanocidal activity in vitro using culture-adapted bloodstream forms of Trypanosoma brucei. The concentrations of tyropeptin A required to reduce the growth rate by 50 % and to kill all cells were 10 and 100 times lower for bloodstream-form trypanosomes than for human leukaemia HL-60 cells, respectively. Enzymatic analysis showed that the trypsin-like activity of the trypanosome proteasome and the chymotrypsin-like activity of the mammalian proteasome are particularly sensitive to inhibition by tyropeptin A. The results suggest that natural compounds targeting the trypsin-like activity of the proteasome may serve as leads for rational drug development of novel anti-trypanosomal agents.
authors.affiliation: Biomedical Research Centre, School of Medicine, Health Policy and Practice, University of East Anglia, Norwich, UK. dsteverding@hotmail.com
authors.forename: Dietmar
authors.initials: D
authors.lastname: Steverding
authors.forename: Alexander J
authors.initials: AJ
authors.lastname: Pemberton
authors.forename: Howard
authors.initials: H
authors.lastname: Royle
authors.forename: Robert W
authors.initials: RW
authors.lastname: Spackman
authors.forename: A Jennifer
authors.initials: AJ
authors.lastname: Rivett
mesh_terms: D000818:Animals; D004151:Dipeptides / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D021261:Parasitic Sensitivity Tests; D008517:Phytotherapy; D010946:Plants, Medicinal; D051381:Rats; D014344:Trypanocidal Agents / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D014346:Trypanosoma brucei brucei / Q000187:drug effects*
chemical_list: D004151:Dipeptides; D014344:Trypanocidal Agents; C449021:tyropeptin A