Synthesis and antiplasmodial activity of new heteroaryl derivatives of 7-chloro-4-aminoquinoline.
Manolo Casagrande, Anna Barteselli, Nicoletta Basilico, Silvia Parapini, Donatella Taramelli, Anna Sparatore
Index: Bioorg. Med. Chem. 20(19) , 5965-79, (2012)
Full Text: HTML
Abstract
With the aim to investigate the effect of different heterocyclic rings linked to the 4-aminoquinoline nucleus on the antimalarial activity, a set of 7-chloro-N-(heteroaryl)-methyl-4-aminoquinoline and 7-chloro-N-(heteroaryl)-4-aminoquinoline was synthesized and tested in vitro against D-10 (CQ-S) and W-2 (CQ-R) strains of Plasmodium falciparum. All compounds exhibited from moderate to high antiplasmodial activities. The activity was strongly influenced both by the presence of a methylenic group, as a spacer between the 4-aminoquinoline and the heterocyclic ring, and by the presence of a basic head. The most potent molecules inhibited the growth of both CQ-S and CQ-R strains of P. falciparum with IC(50)<30 nM and were not toxic against human endothelial cells. These results confirm that the presence of an heteroaryl moiety in the side chain of 7-chloro-4-aminoquinoline is useful for the design and development of new powerful antimalarial agents.Copyright © 2012 Elsevier Ltd. All rights reserved.
Related Compounds
Related Articles:
2008-04-10
[J. Med. Chem. 51(7) , 1995-8, (2008)]
New chimeric antimalarials with 4-aminoquinoline moiety linked to a tetraoxane skeleton.
2008-10-09
[J. Med. Chem. 51(19) , 6216-9, (2008)]
An ELISA test for detecting chloroquine in urine.
1988-01-01
[Trans. R. Soc. Trop. Med. Hyg. 82(2) , 216-20, (1988)]
2012-10-01
[Bioorg. Med. Chem. 20(19) , 5980-5, (2012)]
[J. Chromatogr. A. 345(1) , 209-14, (1985)]