Novel 1-H Phenyl Benzimidazole Derivatives for IBD Therapy - An in-vitro and in-silico Approach to Evaluate its Effects on the IL-23 Mediated Inflammatory Pathway

Abstract

Introduction: Inflammatory Bowel Disease (IBD) is a chronic idiopathic gut condition characterised by recurring and remitting inflammation of the colonic mucosal epithelium. Benzimidazole is a prominent and attractive heterocyclic compound with diverse actions. Although seven locations in the benzimidazole nucleus can be changed with a number of chemical entities for biological activity, benzimidazole fused with a phenyl ring has caught our interest. Methods: To find and optimize novel 1-H phenyl benzimidazole compounds with favorable physicochemical features and drug-like characteristics for the treatment of IBD, in-silico studies and in-vitro approach were used to identify and optimize these derivatives as potent inhibitors of interleukin-23 (IL-23) mediated inflammatory signaling pathway. Results and Discussion: All six compounds exhibit favorable drug-like properties with good intestinal absorption properties. Its high affinity for the target Janus kinase (JAK) and Tyrosine kinase (TYK), which is thought to be a key immunological signaling cascade in the pathophysiology of IBD, is revealed by docking studies. Conclusion: Due totheir effects on decreasing inducible nitric oxide synthase (iNOS) -derived cellular nitritre (NO) release and IL-23-mediated immune signaling by decreasing cyclooxygenase-2 (COX-2) and lipoxygenase (LOX) activity, it's conceivable that the compounds CS3 and CS6 are better options for the treatment of IBD based on in-vitro cell line investigations.