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 IC50 values ranging from 4.21-34.80 & mu;M) 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. A library of 3-substituted-isoindolin-1-ones has been synthesized from 3-alkylidenephtalides and primary amines through one-pot reaction under ultrasonic irradiation. Four isoindolin-1-ones have great potential to be antiplasmodium candidates.

Automated summary

A library of 3-substituted isoindolinones was synthesized using one-pot reaction under ultrasound irradiation. The synthesized compounds showed moderate to strong antiplasmodium activities and low toxicity effects, meeting the drug-likeliness requirements. Among them, four derivatives were identified as potential antiplasmodium candidates.