Amino acid conjugates of 2-mercaptobenzimidazole provide better anti-inflammatory pharmacology and improved toxicity profile
| Autor: | Arif-ullah Khan, Muazzam Arif, Zulkifal Malik, Nadia Shamshad Malik, Muhammad Tariq Khan, Muzaffar Abbas, Ibrahim Javed, Humaira Nadeem |
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| Rok vydání: | 2020 |
| Předmět: |
chemistry.chemical_classification
Benzimidazole Chemistry medicine.drug_class Analgesic Protein Data Bank (RCSB PDB) Pharmacology Carbon-13 NMR Anti-inflammatory Amino acid 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine 030220 oncology & carcinogenesis Drug Discovery medicine Proton NMR Pharmacophore 030217 neurology & neurosurgery |
| Zdroj: | Drug development researchREFERENCES. |
| ISSN: | 1098-2299 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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