Screening of acyl hydrazide proteinase inhibitors for antiparasitic activity against Trypanosoma brucei

Caffrey, Conor R., Schanz, Marvin, Nkemgu-Njinkeng, Joseph, Brush, Matthew, Hansell, Elizabeth, Cohen, Fred E., Flaherty, Terrence M., McKerrow, James H. and Steverding, Dietmar (2002) Screening of acyl hydrazide proteinase inhibitors for antiparasitic activity against Trypanosoma brucei. International Journal of Antimicrobial Agents, 19 (3). pp. 227-231. ISSN 1872-7913

Full text not available from this repository. (Request a copy)

Abstract

The major cysteine proteinase (brucipain) of Trypanosoma brucei is a target for chemotherapy of African Sleeping Sickness. We have screened a non-peptidyl acyl hydrazide proteinase inhibitor library of 500 compounds for inhibition of brucipain. Those 21 compounds with IC(50) values of <40 microM were tested for efficacy against bloodstream forms of T. brucei in cell culture. Eight acyl hydrazides showed 50% or more inhibition of trypanosome replication at <1 microM. The trypanocidal acitivity of the most effective compounds was comparable with those of the commercial antitrypanosomal drugs suramin and diminazene aceturate. However, these acyl hydrazides exhibited varying cytotoxicity towards human HL-60 cells and therefore, only less favourable selectivity indices compared with the commercially available drugs. Nevertheless, the data support the potential of acyl hydrazides as antitrypanosomal chemotherapeutic agents for treatment of sleeping sickness.

Item Type: Article
Additional Information: Errata for this article are available.
Faculty \ School: Faculty of Medicine and Health Sciences > Norwich Medical School
Depositing User: EPrints Services
Date Deposited: 25 Nov 2010 11:09
Last Modified: 24 Jul 2019 17:15
URI: https://ueaeprints.uea.ac.uk/id/eprint/12274
DOI: 10.1016/S0924-8579(01)00488-5

Actions (login required)

View Item View Item