In silico study of ketoprofen's interaction with biomolecules and its biological implications

Abstract

Ketoprofen (KTP) is a widely prescribed nonsteroidal anti-inflammatory drug (NSAID) known for its anti-inflammatory, analgesic, and antipyretic effects. Although generally safe at therapeutic doses, its potential interactions with biologically important molecules at the molecular level remain underexplored. The electronic and chemical reactivity changes that occur when ketoprofen interacts with selected biomolecules of physiological relevance were evaluated using density functional theory (DFT) calculations. The geometries of KTP, ten biomolecules (tryptophan, uric acid, glutathione, asparagine, glycine, proline, glucose, valine, cysteine, glutamic acid), and their complexes were optimized using the DMol(Zhu et al., 2011 [3] ) module in Materials Studio program at the GGA-PBE/DNP level. Key global descriptors (E HOMO , E LUMO , ΔE gap , μ, η, S, χ, ω) and local reactivity indices (Fukui functions) were calculated and discussed. Binding energies of the formed complexes were used to evaluate the thermodynamic parameters. DL-proline exhibited the strongest binding to KTP (binding energy: −0.0299 Ha while tryptophan and glutathione showed the most pronounced changes in electronic descriptors, indicating possible reactivity-driven biochemical effects. Notable trends included decreased ΔE gap and increased electrophilicity in certain complexes, particularly KTP–tryptophan, suggesting potential disruption of electron-transfer pathways. Key reactive sites were identified, with O 8 in KTP consistently acting as the primary electrophilic and nucleophilic center. Generally, KTP forms stable complexes with several biomolecules, potentially altering their electronic and reactive properties. Theoretical findings suggest possible biochemical implications, particularly regarding amino acids involved in neurotransmission (tryptophan) and antioxidant defence (glutathione). Further in vitro and in vivo validation is recommended.