Ultrasound-assisted-one-pot synthesis and antiplasmodium evaluation of 3-substituted-isoindolin-1-ones

As the attempts to control malaria through chemotherapy strategies are restricted, we have prepared a small library of 3-substituted-isoindolinones from (Z)-3-benzylideneisobenzofuran-1(3H)-ones in one-pot fashion under ultrasound irradiation. The one-pot reaction was scalable and efficiently produced the desired products (1a–m) in high yields in a short reaction time. Evaluation of their in vitro antiplasmodium assay against the 3D7 (chloroquine-sensitive) and FCR3 (chloroquine-resistant) strains of Plasmodium falciparum demonstrated that they displayed moderate to strong antiplasmodium activities (the IC(50) values ranging from 4.21–34.80 μM) and low resistance indices. The in silico prediction of ADME and physicochemical properties showed that the synthesized compounds met the drug-likeliness requirements and featured low toxicity effects. Based on the evaluation of the antiplasmodium profiles, 3-substituted-isoindolinone derivatives of 1a, 1d, 1h, and 1l may become potential antiplasmodium candidates.