TY - JOUR
T1 - Design, synthesis and structure-activity relationships of (1H-pyridin-4-ylidene)amines as potential antimalarials
AU - Rodrigues, Tiago
AU - Guedes, Rita C.
AU - dos Santos, Daniel J.V.A.
AU - Carrasco, Marta
AU - Gut, Jiri
AU - Rosenthal, Philip J.
AU - Moreira, Rui
AU - Lopes, Francisca
PY - 2009/7/1
Y1 - 2009/7/1
N2 - (1H-Pyridin-4-ylidene)amines containing lipophilic side chains at the imine nitrogen atom were prepared as potential clopidol isosteres in the development of antimalarials. Their antiplasmodial activity was evaluated in vitro against the Plasmodium falciparum W2 (chloroquine-resistant) and FCR3 (atovaquone-resistant) strains. The most active of these derivatives, 4m, had an IC50 of 1 μM against W2 and 3 μM against FCR3. Molecular modeling studies suggest that (1H-pyridin-4-ylidene)amines may bind to the ubiquinol oxidation Qo site of cytochrome bc1.
AB - (1H-Pyridin-4-ylidene)amines containing lipophilic side chains at the imine nitrogen atom were prepared as potential clopidol isosteres in the development of antimalarials. Their antiplasmodial activity was evaluated in vitro against the Plasmodium falciparum W2 (chloroquine-resistant) and FCR3 (atovaquone-resistant) strains. The most active of these derivatives, 4m, had an IC50 of 1 μM against W2 and 3 μM against FCR3. Molecular modeling studies suggest that (1H-pyridin-4-ylidene)amines may bind to the ubiquinol oxidation Qo site of cytochrome bc1.
KW - (1H-Pyridin-4-ylidene)amines
KW - Antiplasmodial
UR - http://www.scopus.com/inward/record.url?scp=66349136182&partnerID=8YFLogxK
U2 - 10.1016/j.bmcl.2009.05.017
DO - 10.1016/j.bmcl.2009.05.017
M3 - Article
C2 - 19467600
AN - SCOPUS:66349136182
SN - 0960-894X
VL - 19
SP - 3476
EP - 3480
JO - Bioorganic and Medicinal Chemistry Letters
JF - Bioorganic and Medicinal Chemistry Letters
IS - 13
ER -