Synthesis, characterization and biological evaluation of N-Mannich base derivatives of 2-phenyl-2-imidazoline as potential antioxidants, enzyme inhibitors, antimicrobials, cytotoxic and anti-inflammatory agents

Abstract

A series of N-Mannich base derivatives of 2-phenyl-2-imidazoline with substituted amines (1–13) were designed, synthesized, and characterized by spectroanalytical techniques. The newly synthesized compounds (SP1-SP13) were evaluated biologically for their antioxidant, α-amylase enzyme inhibition, antimicrobial, cytotoxic, and anti-inflammatory activities. Compounds were analyzed to predict their drug-likeliness behavior SP11 showed good activity in % FRSA against DPPH free radical at IC50 of 148.16 ± 2.81 µg/mL. SP11 and SP13 exhibited good antioxidant responses in TAC and TRP assays, respectively. SP2 has shown maximum % inhibition against α-amylase enzyme to 94.02 ± 0.2% at 200 µg/mL. SP2, SP8, and SP12 exhibited potent effect against α-amylase enzyme at IC50 value of 9.20 ± 0.48, 10.25 ± 0.43, and 13.81 ± 0.90 µg/mL, respectively. Compounds showed good to moderate activity against all bacterial and fungal strains. The compounds were selected for further analysis against hepatocellular carcinoma cell line (HepG2) based on LD50 and IC50 values obtained in brine shrimp cytotoxicity and biocompatibility assay, respectively. SP3, SP12, and SP13 were evaluated at 24, 48, and 72 h against HepG2 cells. Maximum response was observed at 72 h. A dose-optimization study was conducted and in vivo anti-inflammatory activity was performed on SP3, SP12, and SP13 based on results obtained from in vitro NO assay. The results are compared to that of standard (acetylsalicylic acid).