Synthesis, Characterization, and Biological Evaluation of Some Isoindole-1,3-(2H) Dione Derivatives

Abstract

In this study, we have established promising drug candidates with approved antimicrobial, antioxidant, antileishmanial, and anticancer activities. We hereby report drug likeliness, ADME prediction, synthesis, characterization, and in vitro biological evaluation of isoindole-1,3-(2H) dione derivatives. Synthesized compounds showed a free radical scavenging effect, with compound 1 being the most effective (IC50 value 1.174 μmol/mL). The antibacterial activity of compounds was studied against two microbial Gram-positive and Gram-negative strains by well diffusion method. The inhibition zone of compound 3 is comparable with the inhibition zone of gentamycin at the same concentration. The compounds are highly effective against Leishmania tropica with compound 3 being the most effective one (IC50 0.0478 μmol/mL). The compounds are highly potential for the treatment of Leishmania tropica, and they are more effective than the first-line treatment, Glucantime. Compounds showed good antiproliferative activity against two human cancer cell lines (Caco-2 and HCT-116). Treatment with studied compounds arrests progress throughout the cell cycle and induces apoptosis in cancer cells. Data from structure-activity relationship (SAR) analysis revealed that lipophilic properties of compounds might enhance their activity as antimicrobial, antileishmanial, and antiproliferative activity. The halogenation of isoindole-1,3 (2H) dione moiety increases antimicrobial, antileishmanial, and anticancer activities. Tetra-brominated derivatives are more effective than tetra-chlorinated derivatives.