4-Arylthieno[2,3-b]pyridine-2-carboxamides Are a New Class of Antiplasmodial Agents

Molecules

Tim Gilberger¹  Arne Alder¹  SandraI. Schweda²  Conrad Kunick² 

[1] Centre for Structural Systems Biology, 22607 Hamburg, Germany;Institut für Medizinische und Pharmazeutische Chemie, Technische Universität Braunschweig, 38106 Braunschweig, Germany;

关键词: anti-malarial drugs;    antiplasmodial;    malaria;    PfGSK-3;    Plasmodium falciparum;    thieno[2,3-b]pyridine;   

DOI  :  10.3390/molecules25143187

来源: DOAJ

【 摘 要 】

Malaria causes hundreds of thousands of deaths every year, making it one of the most dangerous infectious diseases worldwide. Because the pathogens have developed resistance against most of the established anti-malarial drugs, new antiplasmodial agents are urgently needed. In analogy to similar antiplasmodial ketones, 4-arylthieno[2,3-b]pyridine-2-carboxamides were synthesized by Thorpe-Ziegler reactions. In contrast to the related ketones, these carboxamides are only weak inhibitors of the plasmodial enzyme PfGSK-3 but the compounds nevertheless show strong antiparasitic activity. The most potent representatives inhibit the pathogens with IC₅₀ values in the two-digit nanomolar range and exhibit high selectivity indices (>100).

【 授权许可】

Unknown