thienopyrimidine has been researched along with Malaria* in 1 studies
1 other study(ies) available for thienopyrimidine and Malaria
| Article | Year |
|---|---|
Discovery of new thienopyrimidinone derivatives displaying antimalarial properties toward both erythrocytic and hepatic stages of Plasmodium.
A preliminary in vitro screening of compounds belonging to various chemical families from our library revealed the thieno[3,2-d]pyrimidin-4(3H)-one scaffold displayed a promising profile against Plasmodium falciparum. Then, 120 new derivatives were synthesized and evaluated in vitro; compared to drug references, 40 showed good activity toward chloroquine sensitive (IC50 35-344 nM) and resistant (IC50 45-800 nM) P. falciparum strains. They were neither cytotoxic (CC50 15-50 μM) toward HepG2 and CHO cells, nor mutagenic. Structure-activity relationships were defined. The lead-compound also appeared active against the Plasmodium liver stages (Plasmodium yoelii IC50 = 35 nM) and a preliminary in vivo evaluation indicated the in vitro activity was preserved (45% reduction in parasitemia compared to untreated infected mice). A mechanistic study demonstrated these molecules do not involve any of the pathways described for commercial drugs and exert a specific activity on the ring and trophozoite stages. Topics: Animals; Antimalarials; Cell Proliferation; CHO Cells; Cricetinae; Cricetulus; Drug Discovery; Erythrocytes; Hep G2 Cells; Humans; Liver; Malaria; Male; Mice; Parasitemia; Plasmodium falciparum; Pyrimidines; Structure-Activity Relationship; Trophozoites | 2015 |