Synthesis and biological evaluation of novel quinoline-piperidine scaffolds as antiplasmodium agents

• DOI: 10.1016/j.ejmech.2020.112330
• Publication Date: 2020-04-23T15:18:24Z
• Authors: Tim Van de Walle; Maya Boone; Julie Van Puyvelde; Jill Combrinck; Peter J. Smith; Kelly Chibale; Sven Mangelinckx; Matthias D’hooghe
• Keywords: Quinoline; Piperidine; Antimalarial Agent; IC50

The parasitic disease malaria places almost half of the world’s population at risk infection and is responsible for more than 400,000 deaths each year. first-line treatment, artemisinin combination therapies (ACT) regimen, under threat due to emerging resistance Plasmodium falciparum strains in e.g. Mekong delta. Therefore, development new antimalarial agents crucial order circumvent growing resistance. Chloroquine, long-established drug, still serves as model compound design quinoline analogues, resulting numerous active derivatives against chloroquine-resistant P. over past twenty years. In this work, a set functionalized decorated with modified piperidine-containing side chain, was synthesized. Both amino- (aminomethyl)quinolines were prepared, total 18 novel quinoline-piperidine conjugates representing four different chemical series. Evaluation their vitro antiplasmodium activity CQ-sensitive (NF54) CQ-resistant (K1) strain unveiled highly potent activities nanomolar range both five 4-aminoquinoline derivatives. Moreover, no cytotoxicity observed all compounds maximum concentration tested. These aminoquinoline hit structures are therefore considerable value research have potency be transformed into upon further hit-to-lead optimization studies.