Journal of Pharmaceutical Research

Abstract

Objective: Benzimidazoles and coumarins are heterocyclic compounds known for their diverse biological and pharmacological properties, such as antibacterial, antifungal, anti-inflammatory, and cytotoxic effects. Derivatives of benzimidazole coumarins have demonstrated promise as antiviral, antineoplastic, and antifilarial agents. This research focuses on the synthesis of benzimidazole coumarin derivatives and evaluates their potential for anti-inflammatory activity. Methodology: Coumarin-3-carboxylic acid was synthesized via the Perkin rearrangement of salicylaldehyde and diethylmalonate. This intermediate was then reacted with 4-chloro ortho-phenylenediamine, triethylamine, and ethyl chloroformate to form an amide linkage, resulting in a yellow solid. Subsequent cyclization with polyphosphoric acid produced the benzimidazole-3-coumarin nucleus as a dark yellow solid. Finally, Ullmann coupling with various aryl amines, using L-proline and copper iodide as catalysts, yielded the desired derivatives. These compounds were characterized by melting point analysis, TLC, IR spectroscopy, and NMR spectroscopy. The synthesized derivatives were also evaluated for anti-inflammatory activity using the carrageenan-induced paw edema model in rats. Findings: Compound P-1 exhibited significant dose-dependent activity (p<0.001) at both 100 mg/kg and 200 mg/kg doses, while compound P-2 demonstrated moderate activity. The IR spectra revealed absorption peaks at 3379.89 cm⁻¹ (indicative of N-H groups) and 1335.24 cm⁻¹ (C-N stretching), confirming the presence of the benzimidazole nucleus. The ¹H NMR spectrum further supported these findings with chemical shifts consistent with the benzimidazole structure. Absorption peaks at 1685.45 cm⁻¹ and 1089.81 cm⁻¹ confirmed the presence of the pyrone nucleus, while the multiple peaks between δ 6.7 and 8.5 ppm indicated the formation of benzopyrone. Novelty: Benzimidazole-coumarin hybrids hold promise as new anti-inflammatory agents and warrant further investigation for potential clinical applications.

Keywords: Benzimidazole, Coumarin, Anti­Inflammatory activity, Antibacterial, Anti­ Filarial agents