Synthesis, characterization, anti-ulcer action and molecular docking evaluation of novel benzimidazole-pyrazole hybrids

摘要

A series of six novel benzimidazole-pyrazole hybrid molecules was synthesized and characterized using elemental analysis (CHN) and spectroscopic methods (1HNMR, FT-IR). All the synthesized compounds were evaluated for their in vivo anti ulcerogenic activity using Albino rats (weighing 180鈥?20 g). The interactions between the compounds and active site residues of H+/K+ ATPase were investigated by molecular docking studies using autodock vina 4.0. SCH28080 was used to validate the docking results. Also the drug likeliness of these compounds was predicted using Molinspiration server in light of Lipinski鈥檚 rule of five. All the six synthesized compounds exhibited higher anti-ulcer activity as compared to omeprazole. These novel hybrid compounds showed comparable anti-ulcer potential of 72鈥?3% at dose level of 500 碌g/kg, whereas omeprazole showed 83% anti-ulcer activity at dose level of 30 mg/kg. The results clearly indicate that these novel benzimidazole-pyrazole hybrids can present a new class of potential anti ulcer agents and can serve as new anti-ulcer drugs after further investigation. KeywordsBenzimidazole-pyrazoleAnti-ulcerH+/K+ ATPaseOmeprazoleAutodock vinaMolinspiration BackgroundPeptic ulcer disease is one of the ailments that influence numerous people around the globe particularly in the developing world [1]. About 10% of the world population is affected. As a consequence of peptic ulcer about 15,000 deaths occurs annually [2]. Certain aggressive and protective factors affect the acid release in gastrointestinal tract. Any imbalance in these factors may disrupt the mucosal protection and expose gastrointestinal lining to gastric acid leading to the lesions called ulcers [3]. Various medications including proton pump inhibitors and H2 receptor antagonist are available for the treatment of gastric ulcers, however clinical assessment of these medications have demonstrated side effects, incidence of relapses and drug interactions [4] thus, there is need to identify more effective and safe anti-ulcer agent. The rapidly growing research in this field suggests that, with remedial and nutritional advances, gastric ulcer may become preventable within the next decade. This can be done by strengthening the defense mechanisms of the gastric mucosa and, in parallel, limiting the factors resulting in gastric ulceration. The present study focuses on the development of drugs which can reduce these damaging factors, thus preventing the ulcer formation.