Molecular Docking Studies of 3-diazo-1-methyl-1,3-dihydro-indol-2-one from Anogeissus leiocarpus leaves against some Inflammatory Mediators

Abstract Targeting key proteins in inflammatory pathways can be an effective strategy for developing new anti-inflammatory therapies. This study focused on molecular docking of 3-diazo-1-methyl-1, 3-dihydro-indol-2-one against key molecular targets such as cyclooxygenase 2 (COX-2), prostaglandin E2 (PDE) synthase, tumor necrosis factor (TNF-α), interleukin 1 beta (IL-1β) and N-methyl-D-Aspartate (NMDA) receptor. 3D Structures of COX-2 (PDB ID: 5IKR), NMDA receptor (PDB ID: 5EWJ), PGE-Synthase (PDB ID: 4AL1), TNF-α (PDB ID: 5MU8), and IL-1β (PDB ID: 4G6J) were obtained from protein databank. The 3D format of 3-diazo-1-methyl-1, 3-dihydro-indol-2-one and standard anti-inflammatory drug were downloaded from PubChem database in SDF file. Molecular docking was performed using AutoDock Vina Software. The 2D diagrams and the 3D (surface) views of the protein-ligand interactions renderings were done using Discovery studio software and Pymol software respectively. The Physicochemical, lipophilicity, solubility, pharmacokinetics and Lipinski drug-likeness of the compound and standard drug were determined using SwissADME Server. The docking results revealed that 3-diazo-1-methyl-1, 3-dihydro-indol-2-one exhibited strong binding affinity towards COX-2 (-7.2 kcal/mol). ADME-T analysis revealed that the compound possess favorable ADMET profiles indicating good oral bioavailability, metabolic stability and low toxicity. It was concluded that 3-diazo-1-methyl-1, 3-dihydro-indol-2-one could be a useful candidate for further development into an anti-inflammatory drug.