Synthesis and antiplasmodial activity of new heteroaryl derivatives of 7-chloro-4-aminoquinoline

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• 作者：Manolo Casagr ; e ; Anna Barteselli ; Nicoletta Basilico ; Silvia Parapini ; Donatella Taramelli ; Anna Sparatore
• 关键词：Antimalarial agents ; 4-Aminoquinoline derivatives ; Chloroquine ; Plasmodium falciparum
• 刊名：Bioorganic and Medicinal Chemistry
• 出版年：2012
• 出版时间：1 October, 2012
• 年：2012
• 卷：20
• 期：19
• 页码：5965-5979
• 全文大小：1013 K

文摘

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 IC₅₀ < 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.