Synthesis and Evaluation of Disubstituted Benzimidazole Derivatives as Potential Analgesic and Antidiarrheal Agents

Abstract

The present study is aimed at the synthesis and biological evaluation of a variety of disubstituted benzimidazole derivatives. The disubstituted benzimidazoles, identified as 3a, 3b, 3c, and 3d were synthesized through condensation of o-phenylenediamine compounds with aromatic aldehydes in the presence of ammonium salt as a catalyst and characterized by infrared spectroscopy and 1H nuclear magnetic resonance spectra. The compounds were screened for analgesic and antidiarrheal activities using acetic acid-induced writhing and castor oil-induced diarrhea models, respectively in Swiss mice. Compounds 3c, 3a, and 3b at a dose of 25 mg/kg decreased the number of writhes by 88.81, 69.40 and 64.93 %, respectively (P<0.05) as compared to standard aceclofenac (88.81 %). Derivatives 3d and 3a displayed promising antidiarrheal activity (P<0.05) at both 25 (inhibition of defecation 67.64 and 56.45 %, respectively) and 50 mg/kg dose levels (80.65 and 75.81% inhibition respectively) in comparison to standard loperamide (85.48% inhibition at a dose of 25 mg/kg). Among the synthesized derivatives, 3a emerged as the most effective analgesic and antidiarrheal agent, and it might be employed as a lead compound for future investigation.