Syntheses and Molecular Docking of New Chloroquine Derivatives as Potential Antiplasmodial and Antioxidant Agents

Abstract

Quinoline is a privileged pharmacophore in many bioactive compounds possessing antimalarial activity. In this paper, some novel 4-aminoquinoline derivatives were synthesized in good yields in order to investigate their antimalarial and antioxidant properties. This was achieved by combining Nʹ-(7-chloroquinolin-4-yl)propane-1,3-diamine 7 with various boc-amino acids. Amongst the synthesized derivatives, tert-buty(1-((3-((7-chloroquinolin-4- yl)amino)propyl)amino)-4-methyl-1-oxopenta-2-yl)carbamate (IC50 = 1.11 mg/mL) and tert- butyl 2-((3-((7-chloroquinolin-4-yl)amino)propyl)carbamoyl)pyrrolidine-1-carboxylate (IC50 =
1.30 mg/mL) exhibit relatively better antiplasmodial activities compared to chloroquine diphosphate (IC50 = 0.84 mg/mL). In addition, tert-butyl(2-((3-((7-chloroquinolin-4- yl)amino)propyl)amino)-2-oxoethyl)carbamate exhibited better antioxidant activity (IC50 = 0.48 mg/mL) than ascorbic acid (IC50 = 0.41 mg/mL).