Amino acid conjugates of 2‐mercaptobenzimidazole provide better anti‐inflammatory pharmacology and improved toxicity profile. Issue 8 (11th August 2020)

• Record Type: Journal Article
• Authors: Khan, Muhammad T.; Nadeem, Humaira; Khan, Arif‐ullah; Abbas, Muzaffar; Arif, Muazzam; Malik, Nadia Shamshad; Malik, Zulkifal; Javed, Ibrahim
• Is Part Of: Drug development research. Volume 81:Issue 8(2020)
• Page Start: 1057
• Page End: 1072
• Publication Date: 2020-08-11
• Subjects: analgesic -- anti‐inflammatory -- benzimidazoles -- gastroprotective -- in‐silico studies; Drug development -- Periodicals; Drugs -- Research -- Periodicals; 615.19
• DOI: 10.1002/ddr.21728
• Languages: English
• ISSNs: 0272-4391

Abstract

Abstract: Benzimidazole is an important pharmacophore for clinically active drugs against inflammation and treatment of pain, however, it is associated with gastrointestinal side effects. Here we synthesized benzimidazole based agents with significant analgesic/anti‐inflammatory potential but with less gastrointestinal adverse effects. In this study, we synthesized novel, orally bioavailable 2‐mercaptobenzimidazole amino acid conjugates (4a–4o ) and screened them for analgesic, anti‐inflammatory and gastro‐protective effects. The synthesized 2‐mercaptbenzimidazole derivatives were characterized for their structure using FTIR, 1 H NMR and 13 C NMR spectroscopic techniques. The 2‐mercaptobenzimidazole amino acid conjugates have found to possess potent analgesic, anti‐inflammatory and gastroprotective activities, particularly with compound 4j and 4k . Most of the compounds exhibited remarkable anti‐ulcer and antisecretory effects. Molecular docking studies were carried out to study the binding affinities and interactions of the synthesized compounds with target proteins COX‐2 (PDB ID: 3LN1) and H + /K + ‐ATPase (PDB ID: 5Y0B). Our results support the clinical promise of these newly synthesized 2‐mercaptobezimidazol conjugates as a component of therapeutic strategies for inflammation and analgesia, for which the gastric side effects are always a major limitation.