Discovery of fast-acting dual-stage antimalarial agents by profiling pyridylvinylquinoline chemical space via copper catalyzed azide-alkyne cycloadditions.

To identity fast-acting, multistage antimalarial agents, a series of pyridylvinylquinoline-triazole analogues have been synthesized via CuAAC. Most of the compounds display significant inhibitory effect on the drug-resistant malarial Dd2 strain at low submicromolar concentrations. Among the tested analogues, compound 60 is the most potent molecule with an EC value of 0.

Synthesis, Structure-Activity Relationship, and Antimalarial Efficacy of 6-Chloro-2-arylvinylquinolines.

There is an urgent need to develop new efficacious antimalarials to address the emerging drug-resistant clinical cases. Our previous phenotypic screening identified styrylquinoline as a promising antimalarial compound. To optimize , we herein report a detailed structure-activity relationship study of 2-arylvinylquinolines, leading to the discovery of potent, low nanomolar antiplasmodial compounds against a CQ-resistant Dd2 strain, with excellent selectivity profiles (resistance index < 1 and selectivity index > 200).