There are around 500 million clinical cases of malaria each year and about
1-2 million people die from this debilitating disease. There is an urgent need
for the development of new drugs because of drug resistance issues. New
drugs should have novel mechanisms of action to prevent cross-resistance with
existing drugs. Some novel, drug-like and selective inhibitors of the enzyme,
deoxyuridine triphosphate nucleotidohydrolase (dUTPase) from Plasmodium
falciparum, the causative agent of malaria have been discovered. The role of
this enzyme is to hydrolyse dUTP to dUMP, maintaining a low dUTP:dTTP ratio.
The aim of this project is to optimise these early lead molecules to generate
late-stage leads or preclinical drug candidates.
The project will include:
- Medicinal chemistry activities for the preparation and optimisation of
- ADME-Tox assays to ensure that the compounds have correct “druglike”
- Biological evaluation to determine the efficacy of the compounds
- Mode of action studies
- Crystallography of inhibitors with the enzyme active site to assist in the
drug design process.
As part of a Framework 5 programme (QLRT-2001-00305), the project team
discovered a novel class of inhibitors, which selectively inhibit dUTPase form
Plasmodium falciparum, the causative agent of malaria.
The aim is to optimise these early lead molecules in order to generate
advanced leads or preclinical drug candidates.
The expected results are compounds that are advanced leads or preclinical
drug candidates for the treatment of malaria.
The potential applications of outputs of this project are compounds, which
could go through to preclinical development for the treatment of malaria and
if successful proceed to clinical trials.
School of Life Sciences
University of Dundee
MSI/WTB/CIR Complex - Dow Street
Dundee DD1 5EH UK
Tel: +44 1382 731 438
Fax: +44 1382 386 373
|2||Nils Gunnar Johansson
S-141 44 Huddinge
|Tel: +46 8 608 3100|
Fax: +46 8 608 3199
|3||Dolores González Pacanowska
||Instituto de Parasitología y Biomedicina
Consejo Superior de Investigaciones
Avda. del Conocimiento s/n
Parque Tecnológico de Ciencias
de la Salud
18100 - Armilla -
|Tel: +34 958 181631/181621|
Fax: +34 958 181633
||Structure Biology Laboratory
Department of Chemistry
University of York
York YO10 5YW
|Tel: +44 1904 328259|
Fax: +44 1904 328266
||Swiss Tropical Institute
|Tel: +41 61 284 82 31
Fax: +41 61 284 81 01