Novel β-lactam antibiotic derivative and its complexes: DFT, frontier energy levels, DNA interaction, docking, physicochemical and antimicrobial properties

Abbas, Abbas M.; Fisal, Sara R.; Orabi, Adel S.

doi:10.1016/j.molstruc.2020.128487

Cited by 11 publications

(4 citation statements)

References 55 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The stretching vibration of the O-H group was associated with a strong broadband at 3419 cm −1 . These bands’ broadening could be due to an intramolecular hydrogen bond [ 12 ].…”

Section: Resultsmentioning

confidence: 99%

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

Abbas,

Nasrallah,

Aboelmagd

et al. 2024

IJMS

Self Cite

View full text Add to dashboard Cite

A new ibuprofen derivative, (E)-2-(4-isobutylphenyl)-N′-(4-oxopentan-2-ylidene) propane hydrazide (IA), was synthesized, along with its metal complexes with Co, Cu, Ni, Gd, and Sm, to investigate their anti-inflammatory efficacy and COX-2 inhibition potential. Comprehensive characterization, including 1H NMR, MS, FTIR, UV–vis spectroscopy, and DFT analysis, were employed to determine the structural configurations, revealing unique motifs for Gd/Sm (capped square antiprismatic/tricapped trigonal prismatic) and Cu/Ni/Co (octahedral) complexes. Molecular docking with the COX-2 enzyme (PDB code: 5IKT) and pharmacokinetic assessments through SwissADME indicated that these compounds have superior binding energies and pharmacokinetic profiles, including BBB permeability and gastrointestinal absorption, compared to the traditional ibuprofen standalone. Their significantly lower IC50 values further suggest a higher efficacy as anti-inflammatory agents and COX-2 inhibitors. These research findings not only introduce promising ibuprofen derivatives for therapeutic applications but also set the stage for future validation and exploration of this new generation of ibuprofen compounds.

show abstract

“…The stretching vibration of the O-H group was associated with a strong broadband at 3419 cm −1 . These bands’ broadening could be due to an intramolecular hydrogen bond [ 12 ].…”

Section: Resultsmentioning

confidence: 99%

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

Abbas,

Nasrallah,

Aboelmagd

et al. 2024

IJMS

Self Cite

View full text Add to dashboard Cite

show abstract

“…The stretching vibration of υ(OH) occurs as a broad band centered at 3451 cm −1 . The existence of inter- or intramolecular hydrogen bonds could explain the broadness of these bands [ 32 ]. A robust and sharp band at 3418 cm −1 is related to the stretching vibration of the NH group [ 33 ].…”

Section: Resultsmentioning

confidence: 99%

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

et al. 2022

Self Cite

View full text Add to dashboard Cite

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.

show abstract

“…[ 21 ] The single band which accompanied to (ONO2 − ) indicates the ionization behavior of the nitrate group or acts as a monodentate ligand. [ 4 ] The stretching vibration of the MO and MN bonds was listed in Table 2 as weak bands.…”

Section: Resultsmentioning

confidence: 99%

“…Many reports mention that the complexes derived from some Schiff base ligands gave wide applications in industrial, medicinal, agricultural, or pharmaceutical fields sometimes gave activity and efficiency larger than its components (ligands and the central metal ions). [1][2][3][4] Synthesis, structural investigation, and biological studies of solid chelates derived from some alkaline earth and transition metal complexes with ampicillin and amoxicillin were reported. These complexes have octahedral geometry except Cu(II) complexes which have square planar structure and uranium has pentagonal bipyramidal coordination.…”

Section: Introductionmentioning

confidence: 99%

Enhancement of the biochemical activity of some market antibiotics by chemical modification: Synthesis, characterization, and biochemical evaluation

Abbas

Fisal

Orabi

2020

J Chinese Chemical Soc

Self Cite

View full text Add to dashboard Cite

The reaction of isatin with the Ampicillin gave the new compound: (6R)‐3,3‐dimethyl‐7‐oxo‐6‐(2‐(([E]‐2‐oxoindolin‐3‐ylidene)amino)‐2‐phenylacetamido)‐4‐thia‐1‐azabicyclo[3.2.0]hept ‐ane‐2‐carboxylic acid (HAI). The new complexes derived from HAI and Co(II), Ni(II), Cu(II), Eu(III), and Gd(III) were obtained in pure form. The obtained compounds were characterized by elemental analysis, FTIR, UV–Vis, Fluorescence, 1HNMR, Mass spectra, DTA, TGA, Magnetic susceptibility, X‐ray, AAS, and the conductivity of 0.001 M in DMSO. The obtained data indicated the formation of the target complexes: [Co(HAI)(H2O)(NO3)]NO3.4H2O, [Ni(AI)(H2O)2]Cl.2H2O, [Cu(AI)]Cl.H2O, [Eu(AI)(H2O)Cl]Cl.5H2O and [Gd(AI)(H2O)(NO3)]NO3.3H2O. The ligation sites were predicted from the guide of the FTIR and thermal analysis meanwhile the stereochemistry was proved by the UV–Vis and magnetic moment. Co(II) and Ni(II) gave an octahedral structure while Cu(II) gave a square planar form. Molecular modeling, molecular mechanics, and DFT calculations were carried out for the synthesized compounds. The active lone pair and surface properties were obtained and discussed in the silico level. The x‐ray analysis indicates the nanoparticle behavior of the Cu‐AI complex with a monoclinic structure. The interactions of the synthesized complexes with FM‐DNA moiety were investigated through spectrometric titration (UV–vis. spectra) and by using fluorescence spectroscopy. The modes and binding affinities were evaluated and discussed using Benesi–Hildebrand method. Antimicrobial activities of the synthesized compounds have been screened using the disc diffusion method. HAI and Cu‐AI gave activity exceeded the Ampicillin. The docking work was carried using the targeting protein of Escherichia coli FabH (PDB code: 1HNJ). The obtained binding energy was compared and discussed in terms of the in vitro studies.

show abstract

Novel β-lactam antibiotic derivative and its complexes: DFT, frontier energy levels, DNA interaction, docking, physicochemical and antimicrobial properties

Cited by 11 publications

References 55 publications

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

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

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

Enhancement of the biochemical activity of some market antibiotics by chemical modification: Synthesis, characterization, and biochemical evaluation

Contact Info

Product

Resources

About