Design, synthesis and structure-activity relationships of (1H-pyridin-4-ylidene)amines as potential antimalarials.
(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 IC(50) of 1microM against W2 and 3microM against FCR3. Molecular modeling studies suggest that (1H-pyridin-4-ylidene)amines may bind to the ubiquinol oxidation Q(o) site of cytochrome bc(1).
Rodrigues
Tiago
T
iMed.UL, Faculty of Pharmacy, University of Lisbon, Av. Prof. Gama Pinto, 1649-003 Lisbon, Portugal.
Guedes
Rita C
RC
dos Santos
Daniel J V A
DJ
Carrasco
Marta
M
Gut
Jiri
J
Rosenthal
Philip J
PJ
Moreira
Rui
R
Lopes
Francisca
F
D000588:Amines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D000818:Animals; D000962:Antimalarials / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D003198:Computer Simulation; D015195:Drug Design; D004351:Drug Resistance; D014450:Electron Transport Complex III / Q000378:metabolism; D010963:Plasmodium falciparum / Q000187:drug effects*; D011725:Pyridines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D013329:Structure-Activity Relationship
C542865:(1H-pyridin-4-ylidene)amine; D000588:Amines; D000962:Antimalarials; D011725:Pyridines; D014450:Electron Transport Complex III