Facile One-Pot Multi-Component Synthesis, Characterization, Molecular Docking Studies, Biological Evaluation of 1,2,4-Triazolo Isoindoline-1,3-Diones and Their DFT Calculations

Alkyl/aralkyl/phenacyl thiotriazolyl isoindoline-1,3-diones were synthesized by the reaction of dipotassium cyanodithioimidocarbonate salt with hydrazine hydrate, phthalic anhydride and alkyl/aralkyl/phenacyl bromides using acetic acid and sodium acetate via a one-pot four-component synthesis. Alternatively, the same final products were also synthesized by the reaction of dipotassium cyanodithioimidocarbonate salt with hydrazine hydrate in presence of acetic acid to give intermediate 5-amino-4H-1,2,4-triazole-3-thiol [I]. This compound was further reacted with phthalic anhydride, followed by a reaction with alkyl/aralkyl/phenacyl bromides to give the title compounds in a two-step process. In this method, the yields are less compared to one-pot four-component synthesis. All the newly synthesized compounds were characterized by their spectral studies (FTIR, H-1-NMR, C-13-NMR, Mass). Further, the synthesized compounds were screened for their in-vitro anticancer activity. Compounds 5 m, 5p, 5r showed good cytotoxic assay against Hela cancer cell lines. Furthermore, compounds 5(a-t) were subjected to their docking analysis and DFT calculations.