A Novel Ibuprofen Derivative and Its Complexes: Physicochemical Characterization, DFT Modeling, Docking, In Vitro Anti-Inflammatory Studies, and DNA Interaction

Abstract

A novel derivative of ibuprofen and salicylaldehyde N′-(4-hydroxybenzylidene)-2-(4-isobutylphenyl) propane hydrazide (HL) was synthesized, followed by its complexation with Cu, Ni, Co, Gd, and Sm. The compounds obtained were characterized by 1HNMR, mass spectrometry, UV-Vis spectroscopy, FT-IR spectroscopy, thermal analysis (DTA and TGA), conductivity measurements, and magnetic susceptibility measurements. The results indicate that the complexes formed were [Cu(L)(H2O)]Cl·2H2O, [Ni(L)2], [Co(L)2]·H2O, [Gd(L)2(H2O)2](NO3)·2H2O and [Sm(L)2(H2O)2](NO3)·2H2O. The surface characteristics of the produced compounds were evaluated by DFT calculations using the MOE environment. The docking was performed against the COX2 targeting protein (PDB code: 5IKT Homo sapiens). The binding energies were −7.52, −9.41, −9.51, −8.09, −10.04, and −8.05 kcal/mol for HL and the Co, Ni, Cu, Sm, and Gd complexes, respectively, which suggests the enhancement of anti-inflammatory behaviors compared with the binding energy of ibuprofen (−5.38 kcal/mol). The anti-inflammatory properties of the new compounds were assessed in vitro using the western blot analysis method and the enzyme-linked immunosorbent assay (ELISA), consistent with the outcomes obtained from docking. The half-maximal inhibitory concentration (IC50) values are 4.9, 1.7, 3.7, 5.6, 2.9, and 2.3 µM for HL and the Co, Ni, Cu, Sm, and Gd complexes, respectively, showing that they are more effective inhibitors of COX2 than ibuprofen (IC50 = 31.4 µM). The brain or intestinal estimated permeation method (BOILED-Egg) showed that HL and its Co complex have high gastrointestinal absorption, while only the free ligand has high brain penetration. The binding constants of Co, Cu, and Gd complexes with DNA were recorded as 2.20 × 104, 2.27 × 106, and 4.46 × 103 M−1, respectively, indicating the intercalator behavior of interaction. The newly synthesized ibuprofen derivative and its metal complexes showed greater anti-inflammatory activity than ibuprofen.

Design, Synthesis, Anti-Inflammatory Activity, DFT Modeling and Docking Study of New Ibuprofen Derivatives

“…We used a conventional approach that was employed frequently in the literature [ 5 , 51 , 52 , 53 ], with some variety in the time of reflux, to synthesize the ester ethyl 2-(4-isobutyl phenylopanoate (IE) and the hydrazine [2-(4-isobutylphenyl)propane hydrazide (HI)].…”

Optically amended biosynthesized crystalline copper-doped ZnO for enhanced antibacterial activity

“…According to a previous report, CuO has the potential to penetrate the cells of microorganisms as well as accumulate in the cell. 48,49 Cu has a high affinity to x oxygen, and generating ROS causes intracellular damage. 48 Doping of ZnO and CuO has been shown to impart a synergistic effect and improve antibacterial property.…”

“…48,49 Cu has a high affinity to x oxygen, and generating ROS causes intracellular damage. 48 Doping of ZnO and CuO has been shown to impart a synergistic effect and improve antibacterial property. 47 We also observed a signicant enhancement of antibacterial activity by GNCs compared to ZnO and CuO GNPs.…”

Bio-oriented synthesis of ibuprofen derivatives for enhancement efficacy in post-operative and chronic inflammatory pain models

“…5.4. Synthesis of ibuprofen imine with benzaldehyde (NS3) 10,11 and ibuprofen imine with salicylaldehyde (NS4) 12,13 The resulting ibuprofen hydrazide compound (NS2) were reacted with benzaldehyde or salicylaldehyde in specic mole concentration in a reux condenser using ethanol as a solvent. The reactions were monitored with thin layer chromatography until the completion of the reaction and to conrm the formation of product.…”

“…There are numbers of ibuprofen derivatives that have been previously synthesized. [8][9][10][11][12][13][14][15] In this study, various ibuprofen derivatives (NS1-NS4) were synthesized, characterized and tested in vivo in the postoperative pain and inammatory animal models. Thus, to the best of our knowledge, this is the rst study that has carried out extensive evaluation of these derivatives for their antinociceptive potential using single repeated dose paradigms of postoperative and inammatory pain.…”