Design-based synthesis, molecular docking analysis of an anti-inflammatory drug, and geometrical optimization and interaction energy studies of an indole acetamide derivative

The new indole acetamide, N-(2-(2-(4-Chlorophenoxy)acetamido)phenyl)-2-carboxamide-1H-indole (5) has been synthesized with good yield by stirring the compound N-(2-Aminophenyl)-2-(4-chlorophenoxy)acetamide (3) with 1H-indole-2-carboxylic acid (4), in dry dichloromethane (DCM) followed by the addition of lutidine, and N,N,N',N'-O-(Benzotriazole-1-yl)-tetramethyluronium tetrafluoroborate (TBTU) in cooled condition. The compound obtained was characterized by spectroscopic analyses (MS, FT-IR, H-1 NMR, C-13 NMR, UVevisible, and elemental). The anti-inflammatory activity was confirmed by in silico modeling study, which target the cyclooxygenase COX-1 and 2 domains. The three-dimensional structure was determined using single crystal X-ray diffraction studies. Geometry optimization of the compound was done using density functional theory calculations by employing B3LYP hybrid functional basis set. Vibrational analysis of the compound revealed that the optimized structure is not in an excited state. Frontier molecular orbitals Highest Occupied Molecular Orbital (HOMO) and Lowest Unoccupied Molecular Orbital (LUMO) were analyzed to understand the electronic charge transfer within the molecule. To analyze the intermolecular interactions in the crystal, Hirshfeld surface analysis was carried out. Energy frameworks were constructed to investigate the stability of the compound. Atom in molecule (AIM) calculations were performed to validate the different intramolecular interactions. (C) 2019 Elsevier B.V. All rights reserved.