Document Type
Article
Publication Date
11-2022
Publication Title
Molecules
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 (HNMR)-H-1, 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 center dot 2H(2)O, [Ni(L)(2)], [Co(L)(2)]center dot H2O, [Gd(L)(2)(H2O)(2)](NO3)center dot 2H(2)O and [Sm(L)(2)(H2O)(2)](NO3)center dot 2H(2)O. 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 mu M 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 mu M). 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 x 10(4), 2.27 x 10(6,) and 4.46 x 10(3) 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.
Keywords
Recommended Citation
Abbas, Abbas M.; Aboelmagd, Ahmed; Kishk, Safaa M.; Nasrallah, Hossam H.; Boyd, W. Christropher; Kalil, Haitham F.; and Orabi, Adel S., "A Novel Ibuprofen Derivative and Its Complexes: Physicochemical Characterization, DFT Modeling, Docking, In Vitro Anti-Inflammatory Studies, and DNA Interaction" (2022). Chemistry Faculty Publications. 633.
https://engagedscholarship.csuohio.edu/scichem_facpub/633
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.
DOI
10.3390/molecules27217540
Version
Publisher's PDF
Volume
27
Issue
21
