Bioorganic & Medicinal Chemistry 2012-10-01

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)

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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.