MOLECULAR DOCKING, DESIGN, SYNTHESIS, IN VITRO ANTIOXIDANT AND ANTI-INFLAMMATORY EVALUATIONS OF NEW ISOQUINOLINE DERIVATIVES
Keywords:Antioxidant, N-arylhomophthalimides, Anti-inflammation, (E)-4arylidne-2-(4 chlorophenyl) isoquinoline 1, 3-dione, Molecular Docking
Objectives: To design and synthesis N-substituted (E)-4-arylidene-isoquinoline-1,3-dione derivatives as anti-inflammatory and antioxidant drug moieties using molecular docking as a tool.
Methods: The structure of compounds (5a-h) was elucidated by means of FT-IR, GC-MS and NMR spectroscopy. Molecular docking was carried out to clarify the molecular aspects of the observed COX-inhibitory activities of the investigated compounds. DPPH radical scavenging analysis method was used to determine antioxidant activity and in-vitro anti-Inflammatory activity was conducted by Human Red Blood Cell (HRBC) membrane stabilization method utilizing Diclofenac sodium as standard.
Results: Isoquinoline (N-substituted (E)-4-arylidene-isoquinoline-1,3-dione) derivatives were achieved using oxalic acid as the catalyst, by aldol condensation of the corresponding aldehydes and the corresponding N-substituted homophthalimides with a maximum yield of 92%. Ligand efficiency (LE) consequences being a clear indication that the action potential of the compounds 5e (-0.72) and 5d (-0.64) is high when compare with the standard (-0.63) for COX-1. While for COX-2, compounds 5e (-0.81) 5d (-0.79) and 5h (-0.98) were shown a remarkable ligand efficiency than the standard (-0.65). Anti-inflammatory and antioxidant studies on the compounds 5h<5d<5g was found best activity results.
Conclusion: From our overall studies, it was understood that the activities of both in silico and in vitro anti-inflammatory results are coincide together. The p-values were significant for all the compounds 5(a-h) in both COX-1 and COX-2 activities which indicate that all the compounds have â€˜competency' towards druggability for both anti-inflammatory and antioxidant, especially the compounds 5h<5d<5g<5e can be suggested for in vivo.
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