Synthesis, characterization and in vitro, in vivo, in silico biological evaluations of substituted benzimidazole derivatives.

Abstract

A series of substituted benzimidazole derivatives were synthesized by reacting O-phenylenediamine with various aromatic aldehydes or glycolic acid using various inexpensive reagents in aqueous media. Synthesized compounds were characterized and elucidated by IR, 1H NMR, ESI-MS spectra. Resultant compounds were screened for in vitro antimicrobial, cytotoxic, antioxidant, lipid peroxidation and cholinesterase inhibitory activities, in vivo analgesic and anti-inflammatory, and in silico anti-acetylcholinesterase and anti-butyrylcholinesterase activities. Among the synthesized compounds, compound 3b showed most promising central analgesic effect (46.15%) compared to morphine (48.08%), whereas compounds 6, 3c and 3a showed significant peripheral analgesic activity at two different dose levels (25mg/kg and 50mg/kg). Compounds 3b and 3a at the dose of 100mg/kg showed significant anti-inflammatory effects from the first hour and onward, whereas compounds 6 and 3b showed moderate cytotoxic activities. In addition, compound 3a showed significant antioxidant activity having IC50 value of 16.73µg/ml compared to 14.44µg/ml for the standard BHT. Compound 6, 3a and 3b exhibited mild to moderate cholinesterase inhibitory activity. In silico studies revealed that compound 3a and 3b might be suitable for cholinesterase inhibitory activity. A comprehensive computational and experimental data suggested compounds 3b and 3a as the best possible candidates for pharmacological activity. All the experimental data were statistically significant (p<0.01 level).