Understanding the selectivity of nonsteroidal anti-inflammatory drugs for cyclooxygenases using quantum crystallography and electrostatic interaction energy
Quantum crystallography methods have been employed to investigate complex formation between nonsteroidal anti-inflammatory drugs (NSAIDs) and cyclooxygenase (COX) enzymes, with particular focus on the COX-1 and COX-2 isoforms. This study analyzed the electrostatic interaction energies of selected NS...
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International Union of Crystallography
2025-03-01
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| Online Access: | https://journals.iucr.org/paper?S2052252525000053 |
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| author | S. Pawlędzio M. Ziemniak X. Wang K. Woźniak M. Malinska |
| author_facet | S. Pawlędzio M. Ziemniak X. Wang K. Woźniak M. Malinska |
| author_sort | S. Pawlędzio |
| collection | DOAJ |
| description | Quantum crystallography methods have been employed to investigate complex formation between nonsteroidal anti-inflammatory drugs (NSAIDs) and cyclooxygenase (COX) enzymes, with particular focus on the COX-1 and COX-2 isoforms. This study analyzed the electrostatic interaction energies of selected NSAIDs (flurbiprofen, ibuprofen, meloxicam and celecoxib) with the active sites of COX-1 and COX-2, revealing significant differences in binding profiles. Flurbiprofen exhibited the strongest interactions with both COX-1 and COX-2, indicating its potent binding affinity. Celecoxib and meloxicam showed a preference for COX-2, consistent with their known selectivity for this isoform, while ibuprofen showed comparable interaction energies with both isoforms, reflecting its nonselective inhibition pattern. Key amino-acid residues, including Arg120, Arg/His513 and Tyr355, were identified as critical determinants of NSAID selectivity and binding affinity. The findings highlight the complex interplay between interaction energy and selectivity, suggesting that while electrostatic interactions play a fundamental role, additional factors such as enzyme dynamics and the hydrophobic effect also contribute to the therapeutic efficacy and safety profiles of NSAIDs. These insights provide valuable guidance for the rational design of NSAIDs with enhanced therapeutic benefits and minimized adverse effects. |
| format | Article |
| id | doaj-art-d931f1a9c88c4640a6a84d902279a7b5 |
| institution | DOAJ |
| issn | 2052-2525 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | International Union of Crystallography |
| record_format | Article |
| series | IUCrJ |
| spelling | doaj-art-d931f1a9c88c4640a6a84d902279a7b52025-08-20T03:00:21ZengInternational Union of CrystallographyIUCrJ2052-25252025-03-0112220822210.1107/S2052252525000053pen5007Understanding the selectivity of nonsteroidal anti-inflammatory drugs for cyclooxygenases using quantum crystallography and electrostatic interaction energyS. Pawlędzio0M. Ziemniak1X. Wang2K. Woźniak3M. Malinska4Neutron Scattering Division, Oak Ridge National Laboratory, Oak Ridge, TN 37831, USAFaculty of Chemistry, Biological and Chemical Research Centre, University of Warsaw, 02-093 Warsaw, PolandNeutron Scattering Division, Oak Ridge National Laboratory, Oak Ridge, TN 37831, USAFaculty of Chemistry, Biological and Chemical Research Centre, University of Warsaw, 02-093 Warsaw, PolandFaculty of Chemistry, Biological and Chemical Research Centre, University of Warsaw, 02-093 Warsaw, PolandQuantum crystallography methods have been employed to investigate complex formation between nonsteroidal anti-inflammatory drugs (NSAIDs) and cyclooxygenase (COX) enzymes, with particular focus on the COX-1 and COX-2 isoforms. This study analyzed the electrostatic interaction energies of selected NSAIDs (flurbiprofen, ibuprofen, meloxicam and celecoxib) with the active sites of COX-1 and COX-2, revealing significant differences in binding profiles. Flurbiprofen exhibited the strongest interactions with both COX-1 and COX-2, indicating its potent binding affinity. Celecoxib and meloxicam showed a preference for COX-2, consistent with their known selectivity for this isoform, while ibuprofen showed comparable interaction energies with both isoforms, reflecting its nonselective inhibition pattern. Key amino-acid residues, including Arg120, Arg/His513 and Tyr355, were identified as critical determinants of NSAID selectivity and binding affinity. The findings highlight the complex interplay between interaction energy and selectivity, suggesting that while electrostatic interactions play a fundamental role, additional factors such as enzyme dynamics and the hydrophobic effect also contribute to the therapeutic efficacy and safety profiles of NSAIDs. These insights provide valuable guidance for the rational design of NSAIDs with enhanced therapeutic benefits and minimized adverse effects.https://journals.iucr.org/paper?S2052252525000053multipole modelnsaidsibuprofenflurbiprofenmeloxicamcelecoxibprotein crystallographyexact potential/multipole modelepmm |
| spellingShingle | S. Pawlędzio M. Ziemniak X. Wang K. Woźniak M. Malinska Understanding the selectivity of nonsteroidal anti-inflammatory drugs for cyclooxygenases using quantum crystallography and electrostatic interaction energy IUCrJ multipole model nsaids ibuprofen flurbiprofen meloxicam celecoxib protein crystallography exact potential/multipole model epmm |
| title | Understanding the selectivity of nonsteroidal anti-inflammatory drugs for cyclooxygenases using quantum crystallography and electrostatic interaction energy |
| title_full | Understanding the selectivity of nonsteroidal anti-inflammatory drugs for cyclooxygenases using quantum crystallography and electrostatic interaction energy |
| title_fullStr | Understanding the selectivity of nonsteroidal anti-inflammatory drugs for cyclooxygenases using quantum crystallography and electrostatic interaction energy |
| title_full_unstemmed | Understanding the selectivity of nonsteroidal anti-inflammatory drugs for cyclooxygenases using quantum crystallography and electrostatic interaction energy |
| title_short | Understanding the selectivity of nonsteroidal anti-inflammatory drugs for cyclooxygenases using quantum crystallography and electrostatic interaction energy |
| title_sort | understanding the selectivity of nonsteroidal anti inflammatory drugs for cyclooxygenases using quantum crystallography and electrostatic interaction energy |
| topic | multipole model nsaids ibuprofen flurbiprofen meloxicam celecoxib protein crystallography exact potential/multipole model epmm |
| url | https://journals.iucr.org/paper?S2052252525000053 |
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