Synthesis, analgesic, anti-inflammatory, COX/5-LOX inhibition, ulcerogenic evaluation, and docking study of benzimidazole bearing indole and benzophenone analogs

• Published in: Journal of molecular structure 2022-07, Vol.1259, p.132741, Article 132741
• Main Authors: Nagesh, Khadri M.J., Prashanth, T., Khamees, Hussien Ahmed, Khanum, Shaukath Ara
• Format: Article
• Language: English
• Subjects: 5-LOX inhibition; Analgesic; Anti-inflammatory; COX-1/COX-2 inhibition; Docking study; Heterocycle; Ulcerogenic evaluation
• ISSN: 0022-2860; 1872-8014
• DOI: 10.1016/j.molstruc.2022.132741

•Synthesis of benzimidazole analogs bearing benzophenone and indole moieties 10a-j.•Screening of synthesized compounds for in vivo analgesic, anti-inflammatory, and ulcerogenic evaluation.•In vitro analysis of COX-1, COX-2, and 5-LOX inhibition.•Molecular docking studies supported the investigation of the ligand binding to their target protein.•Viable dual inhibition of COX/5-LOX by the synthetic analogs. Inflammation therapy is particularly focused on the development of safer non-steroidal anti-inflammatory drugs (NSAIDs), administered to control inflammation. It is typically considered that dual-inhibition of COX/5-LOX, which improves efficacy and has fewer side effects, is an effective technique for combating inflammation. In this perspective, the series of titled compounds (10a-j) were designed, synthesized, and characterized following with the anti-inflammatory, analgesic, and ulcerogenic evaluation. The investigation of the potentiality of the titled compounds (10a-j) displayed a high degree of anti-inflammatory activity. The compounds displaying potential analgesic activity were identified and validated further for evaluation of analgesic, anti-inflammatory activity, and subsequent ulcerogenic evaluation. In addition, the COX-1, COX-2, and 5-LOX analyses were carried out in vitro. Among (10a-j) series, compound 10c with para substitution of fluoro group on the benzoyl ring and two chloro groups at ortho position in phenyl ring of benzophenone was observed to have good inhibitory potency. Furthermore, the in silico docking study was performed by using AutoDock tools docking software.