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Nucleobase derivatives as drugs against trypanosomal diseases

Objective

The protozoan diseases, leishmaniasis, African trypanosomiasis and Chagas’ disease are responsible for substantial global morbidity, mortality, and economic adversity, and in most countries, existing strategies for control and treatment are either failing or under serious threat. New tools for combating pathogenic protozoa and the development and exploitation of new drug targets are required. This proposal builds on several achievements and observations of the consortium in the area of nucleotide metabolism. •Pyrimidine and purine metabolism exhibits unique features in trypanosomes. •The identification of a unique enzyme involved in pyrimidine metabolism restricted to trypanosomes and essential for viability: the dimeric all-alpha dUTPase. •An exceptional collection of purine and pyrimidine analogues is available through the consortium for antiprotozoal screening and lead identification. •The consortium brings together an outstanding combination of expertise for drug discovery. The main objective is the identification of new purine and pyrimidine derivatives for the treatment of the leishmaniases and trypanosomiases. A two-pronged approach is proposed to discover new leads for the treatment of leishmaniasis and trypanosomiasis targeting nucleoside/ nucleotide metabolism. 1)The phenotypic approach exploring the potential of large collections of novel nucleobase derivatives against trypanosomal diseases. 2)The target-based approach specifically centred on the development of inhibitors of the enzyme deoxyuridine triphosphate nucleotidohydrolase. The trypanosomal enzyme shows structural and functional characteristics which differ profoundly from the mammalian counterpart. The aim is to identify potent inhibitors that are active against parasitic protozoa, active in rodent models of infection and have drug-like properties.

Field of science

  • /natural sciences/biological sciences/microbiology/protozoology
  • /natural sciences/biological sciences/genetics and heredity/nucleotide
  • /social sciences/sociology/demography/mortality
  • /natural sciences/biological sciences/biochemistry/biomolecules/proteins/enzymes

Call for proposal

FP7-HEALTH-2007-B
See other projects for this call

Funding Scheme

CP-SICA - Collaborative project for specific cooperation actions dedicated to international cooperation partner countries (SICA)

Coordinator

AGENCIA ESTATAL CONSEJO SUPERIOR DEINVESTIGACIONES CIENTIFICAS
Address
Calle Serrano 117
28006 Madrid
Spain
Activity type
Research Organisations
EU contribution
€ 615 665
Administrative Contact
Alberto Sereno Alvarez (Mr.)

Participants (6)

UNIVERSITY OF DUNDEE
United Kingdom
EU contribution
€ 508 354
Address
Nethergate
DD1 4HN Dundee
Activity type
Higher or Secondary Education Establishments
Administrative Contact
Zoe Kidd (Ms.)
UNIVERSITY OF YORK
United Kingdom
EU contribution
€ 349 658
Address
Heslington
YO10 5DD York North Yorkshire
Activity type
Higher or Secondary Education Establishments
Administrative Contact
Chris Barber (Mr.)
SCHWEIZERISCHES TROPEN- UND PUBLIC HEALTH-INSTITUT
Switzerland
EU contribution
€ 294 312
Address
Socinstrasse 57
CH-4002 Basel
Activity type
Research Organisations
Administrative Contact
Ulrich Wasser (Mr.)
MEDIVIR AB
Sweden
EU contribution
€ 229 599
Address
Lunastigen 7
14144 Huddinge
Activity type
Private for-profit entities (excluding Higher or Secondary Education Establishments)
Administrative Contact
Nils Gunnar Johansson (Dr.)
SYNGENE INTERNATIONAL LIMITED PLC
India
EU contribution
€ 280 200
Address
Jigani Link Road
560 099 Bangalore
Activity type
Private for-profit entities (excluding Higher or Secondary Education Establishments)
Administrative Contact
M. B. Chinappa (Mr.)
INSTITUT PASTEUR DE MONTEVIDEO
Uruguay
EU contribution
€ 279 399
Address
Mataojo 2020
11400 Montevideo
Activity type
Research Organisations
Administrative Contact
Didier Pouzergues (Mr.)