Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: UMLS:C0018799 (
heart disease
)
34,133
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Chagas disease, caused by the parasitic protozoan Trypanosoma cruzi, is the leading cause of
heart disease
in Latin America. T. cruzi
dihydroorotate dehydrogenase
(
DHODH
), which catalyzes the production of orotate, was demonstrated to be essential for T. cruzi survival, and thus has been considered as a potential drug target to combat Chagas disease. Here we report the design and synthesis of 75 compounds based on the orotate structure. A comprehensive structure-activity relationship (SAR) study revealed two 5-substituted orotate analogues (5u and 5v) that exhibit K
i
app
values of several ten nanomolar level and a selectivity of more than 30,000-fold over human
DHODH
. The information presented here will be invaluable in the search for next-generation drug leads for Chagas disease.
...
PMID:Design and synthesis of potent substrate-based inhibitors of the Trypanosoma cruzi dihydroorotate dehydrogenase. 2811 56
