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

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 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) (5c) and tert-butyl2-((3-((7-chloroquinolin-4 yl)amino)propyl)carbamoyl)pyrrolidine-1-carboxylate(IC50 = 1.30mg/mL) (5d) exhibit relatively better antiplasmodial activities compared to chloroquine diphosphate (IC50 = 0.84mg/mL). In addition, tert-butyl2-((3-((7-chloroquinolin-4-yl)amino)propyl)carbamoyl)pyrrolidine-1-carboxylate (5d) (IC50 = 0.48mg/mL) exhibited good antioxidant activity relative to ascorbic acid (IC50= 0.41mg/mL)