SYNTHESIS, ANTIPLASMODIAL, ANTIOXIDANT, AND MOLECULAR DOCKING INVESTIGATION OF NOVEL 4-AMINOQUINOLINE-ISOINDOLIN-1-ONES HYBRIDS

Abstract

Four novel 4-aminoquinoline-isoindolin-1-one hybrids 5a-d have been designed as antiplasmodial and antioxidant agents by combining the 4-aminoquinoline unit and isoindolin-1-one moiety using the flexible alkyl linker. The hybrids were synthesized in two steps via aromatic nucleophilic substitution and nucleophilic addition reactions and were obtained with yields up to 83%. The evaluation of their anti-plasmodial activity was conducted against Plasmodium falciparum 3D7, whereas the antioxidant activity was assessed using the DPPH method. Among the four hybrids, the hybrid of 3-benzyl-2-(6-((7-chloroquinolin-4-yl)amino)hexyl)-3-hydroxyisoindolin-1-one 5c demonstrated excellent antiplasmodial (IC50 of 0.01 µg/mL) and antioxidant (IC50 of 46.58 µg/mL) activities. The molecular docking study was conducted using PfOAT as the protein target. The docking results were in line with the in vitro antiplasmodial assay, where hybrid 5c displayed the lowest binding energy of -8.43 kcal/mol