Novel substituted isoindolinones derived from lawsone: synthesis, characterization, theoretical, biological activity and docking studies

Abstract

An efficient Mannich type multicomponent reaction approach was developed for the synthesis of a series of novel substituted isoindolinones derived from Lawsone, 2-formyl benzoic acid, and various primary amines. This protocol features direct construction of C-N and C-C bonds via metal-free method at room temperature using an environment-friendly solvent. The synthesized isoindolinone compounds 4a-4m were characterized by various spectroscopic techniques such as 1H NMR, 13C NMR, FT-IR, and ESI-MS. Computational studies were carried out by the DFT method using B3LYP/6-31G (d,p) basic set as a tool to analyse the chemical reactivity parameters and comprehend the molecular interaction. The molecular electrostatic potential (MEP), dipole moment, chemical reactivity, and stability features of investigated isoindolinones revealed that 4i, 4j, 4l, and 4m could be promising candidates for further biological activity. The cytotoxic activity of selected compounds was evaluated using MTT assay against HepG2 cell lines (Human liver cancer cell line). The data revealed that screened compounds displayed excellent to moderate activity. The docking examination was executed on a promising liver cancer-associated Alpha fetoprotein (AFP). It showed a positive outcome with minimum binding energy and hydrogen bond interaction. Furthermore, In vivo studies ascertained that synthesized isoindolinone derivatives can lead to enhanced cancer cell death and prevention of tumor growth by restoring serum SGOT and SGPT levels near to normal. It further restores matrix metallopeptidase (MMP-2 and MMP-9 levels) near to control confirms the effectiveness of the compound.