title: Design, synthesis and structure-activity relationships of (1H-pyridin-4-ylidene)amines as potential antimalarials.
abstract: (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).
authors.affiliation: iMed.UL, Faculty of Pharmacy, University of Lisbon, Av. Prof. Gama Pinto, 1649-003 Lisbon, Portugal.
authors.forename: Tiago
authors.initials: T
authors.lastname: Rodrigues
authors.forename: Rita C
authors.initials: RC
authors.lastname: Guedes
authors.forename: Daniel J V A
authors.initials: DJ
authors.lastname: dos Santos
authors.forename: Marta
authors.initials: M
authors.lastname: Carrasco
authors.forename: Jiri
authors.initials: J
authors.lastname: Gut
authors.forename: Philip J
authors.initials: PJ
authors.lastname: Rosenthal
authors.forename: Rui
authors.initials: R
authors.lastname: Moreira
authors.forename: Francisca
authors.initials: F
authors.lastname: Lopes
mesh_terms: 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
chemical_list: C542865:(1H-pyridin-4-ylidene)amine; D000588:Amines; D000962:Antimalarials; D011725:Pyridines; D014450:Electron Transport Complex III