Hafiz Aamir Ali Kharl
Biography
Lecturer, Department of Pharmacy, University of Agriculture, Faisalabad, Pakistan
Research Interest
Abstract
Design, Synthesis and Pharmacological Investigation of Novel 2-Mercaptobenzimidazole Derivatives as Anti-Ulcer Agents
Ulcer may develop at any area of elementary canal including esophagus, stomach, duodenum or other. Any imbalance leads to destruction of mucosal lining of gastrointestinal tract resulting in peptic ulcer. The unique structural features of benzimidazole and a wide range of biological activities of its derivatives made it a privileged structure in drug discovery.
20 different chalcones were prepared by reacting substituted aldehydes with ketones, these chalcones were condensed with benzimidazole-pyrazole hybrids to give final products (M3a–M3t). Docking and In-silico studies were done by utilizing AutoDockVina and online tools (SWISS ADME).
The chemical structures of 2-mercaptobenzimidazole derivatives were confirmed by FTIR, 1HNMR and 13CNMR spectroscopic data. Molecular docking studies were carried out to predict the binding affinities and interactions of the synthesized compounds with target proteins CA-II (PDB ID: 1A42), and H+ /K+ -ATPase (PDB ID: 5YLU). These derivatives were screened for In-vitro antioxidant potential (DPPH), CA-II, ex-vivo H+ /K+ ATPase assay and in-vivo ethanol-induced gastric ulcer in rats among these M3e, M3i and M3m showed promising results (IC50 = 17.76 μM, 20.73 μM and 30.69 μM), M3e and M3m showed significant results (IC50 = 41.49 μM and 27 μM), M3i and M3m showed enhanced activity 38.82± 3 and 42.45± 2.52. The compound M3e, M3i, M3m exhibited maximum anti-ulcer activity and reduced the ulcer region by, 68 ± 3%, 74 ± 5%, 81 ± 5% respectively.
The results obtained from molecular docking studies of synthesized compounds were also in conjunction with their in-vitro, in-vivo and ex-vivo pharmacological activities. Results support that compounds M3e, M3i and M3m have potent anti-ulcer and antioxidant activities.
Keywords: Ulcer, Drug discovery, Molecular docking, Lipinski’s Rule, Carbonic Anhydrase.
