Design, Synthesis, Anti-Inflammatory Activity, DFT Modeling and Docking Study of New Ibuprofen Derivatives
A new ibuprofen derivative, (<i>E</i>)-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 charac...
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| Format: | Article |
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MDPI AG
2024-03-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/25/6/3558 |
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| author | Abbas M. Abbas Hossam H. Nasrallah Ahmed Aboelmagd Safaa M. Kishk W. Christopher Boyd Haitham Kalil Adel S. Orabi |
| author_facet | Abbas M. Abbas Hossam H. Nasrallah Ahmed Aboelmagd Safaa M. Kishk W. Christopher Boyd Haitham Kalil Adel S. Orabi |
| author_sort | Abbas M. Abbas |
| collection | DOAJ |
| description | A new ibuprofen derivative, (<i>E</i>)-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 <sup>1</sup>H 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. |
| first_indexed | 2024-04-24T18:09:51Z |
| format | Article |
| id | doaj.art-073a3b2be3bf4a14a05c8b87849a835a |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-04-24T18:09:51Z |
| publishDate | 2024-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-073a3b2be3bf4a14a05c8b87849a835a2024-03-27T13:46:28ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672024-03-01256355810.3390/ijms25063558Design, Synthesis, Anti-Inflammatory Activity, DFT Modeling and Docking Study of New Ibuprofen DerivativesAbbas M. Abbas0Hossam H. Nasrallah1Ahmed Aboelmagd2Safaa M. Kishk3W. Christopher Boyd4Haitham Kalil5Adel S. Orabi6Chemistry Department, Faculty of Science, Suez Canal University, Ismailia 41522, EgyptChemistry Department, Faculty of Science, Suez Canal University, Ismailia 41522, EgyptChemistry Department, Faculty of Science, Suez Canal University, Ismailia 41522, EgyptMedicinal Chemistry Department, Faculty of Pharmacy, Suez Canal University, Ismailia 41522, EgyptChemistry Department, College of Arts and Sciences, Cleveland State University, Cleveland, OH 44115, USAChemistry Department, Faculty of Science, Suez Canal University, Ismailia 41522, EgyptChemistry Department, Faculty of Science, Suez Canal University, Ismailia 41522, EgyptA new ibuprofen derivative, (<i>E</i>)-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 <sup>1</sup>H 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.https://www.mdpi.com/1422-0067/25/6/3558ibuprofenanti-inflammatoryacetylacetoneDFTdockingcomplexes |
| spellingShingle | Abbas M. Abbas Hossam H. Nasrallah Ahmed Aboelmagd Safaa M. Kishk W. Christopher Boyd Haitham Kalil Adel S. Orabi Design, Synthesis, Anti-Inflammatory Activity, DFT Modeling and Docking Study of New Ibuprofen Derivatives International Journal of Molecular Sciences ibuprofen anti-inflammatory acetylacetone DFT docking complexes |
| title | Design, Synthesis, Anti-Inflammatory Activity, DFT Modeling and Docking Study of New Ibuprofen Derivatives |
| title_full | Design, Synthesis, Anti-Inflammatory Activity, DFT Modeling and Docking Study of New Ibuprofen Derivatives |
| title_fullStr | Design, Synthesis, Anti-Inflammatory Activity, DFT Modeling and Docking Study of New Ibuprofen Derivatives |
| title_full_unstemmed | Design, Synthesis, Anti-Inflammatory Activity, DFT Modeling and Docking Study of New Ibuprofen Derivatives |
| title_short | Design, Synthesis, Anti-Inflammatory Activity, DFT Modeling and Docking Study of New Ibuprofen Derivatives |
| title_sort | design synthesis anti inflammatory activity dft modeling and docking study of new ibuprofen derivatives |
| topic | ibuprofen anti-inflammatory acetylacetone DFT docking complexes |
| url | https://www.mdpi.com/1422-0067/25/6/3558 |
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