Design, synthesis and structure-activity relationships of (1H-pyridin-4-ylidene)amines as potential antimalarials

Tiago Rodrigues; Rita C Guedes; Daniel J V A dos Santos; Marta Carrasco; Jiri Gut; Philip J Rosenthal; Rui Moreira; Francisca Lopes

doi:10.1016/j.bmcl.2009.05.017

Design, synthesis and structure-activity relationships of (1H-pyridin-4-ylidene)amines as potential antimalarials

Bioorg Med Chem Lett. 2009 Jul 1;19(13):3476-80. doi: 10.1016/j.bmcl.2009.05.017. Epub 2009 May 9.

Authors

Tiago Rodrigues¹, Rita C Guedes, Daniel J V A dos Santos, Marta Carrasco, Jiri Gut, Philip J Rosenthal, Rui Moreira, Francisca Lopes

Affiliation

¹ iMed.UL, Faculty of Pharmacy, University of Lisbon, Av. Prof. Gama Pinto, 1649-003 Lisbon, Portugal.

PMID: 19467600
DOI: 10.1016/j.bmcl.2009.05.017

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).

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Amines / chemical synthesis
Amines / chemistry*
Amines / pharmacology
Animals
Antimalarials / chemical synthesis
Antimalarials / chemistry*
Antimalarials / pharmacology
Computer Simulation
Drug Design
Drug Resistance
Electron Transport Complex III / metabolism
Plasmodium falciparum / drug effects*
Pyridines / chemical synthesis
Pyridines / chemistry*
Pyridines / pharmacology
Structure-Activity Relationship

Substances

(1H-pyridin-4-ylidene)amine
Amines
Antimalarials
Pyridines
Electron Transport Complex III