Spectrochemical, medicinal, and toxicological studies of ketoprofen and its newly designed analogs; quantum chemical, and drug discovery approach

Nonsteroidal anti-inflammatory drugs (NSAIDs) are commonly used as analgesics, antipyretics, anti-clotting, and anti-inflammatory agents. One such NSAID, ketoprofen (KTP), is prescribed to treat pain, sprains, menstrual irregularities, osteoarthritis (OA), and rheumatoid arthritis (RA). By inhibiting cyclooxygenase, it halts prostaglandin synthesis. However, it exhibits significant side effects in humans and other living things. Herein, the chemical structure of KTP has been modified to search for improved chemical and medicinal effects. Density functional theory (DFT) has been employed for geometry optimization. Molecular docking and molecular dynamics (MD) simulations were conducted to investigate the binding affinity and stability of the protein-drug complex with prostaglandin synthase protein. ADMET predictions were carried out to calculate and compare the pharmacokinetic behavior of KTP and its new analogs. Spectral and chemical results support the structural conformation of the new analogs, all of which exhibit improved physicochemical, and binding properties compared to the parent drug. After a 100 ns MD simulation, the drugs remained tightly bound to the binding site of the receptor protein, showing significant interactions with shorter distances among the new analogs. The ADMET predictions confirmed better pharmacokinetic properties of novel analogs compared to KTP. The study compares several KTP metabolites using thermo-chemical, spectral, biological, and toxicological analysis. Results showed the reactivity and stability, with spectral data evaluating all KTP analogs. ADMET predicts that all KTP derivatives are less toxic and have better pharmacokinetic features than KTP. Most KTP analogs exhibit excellent oral bioavailability and significant analgesic, antipyretic, and anti-inflammatory functions. These findings support the potential use of these drugs in the future drugs.