Modification of ibuprofen to improve the medicinal effect; structural, biological, and toxicological study.

Ibuprofen is classified as a non-steroidal anti-inflammatory drug (NSAID) that is employed as an initial treatment option for its non-steroidal anti-inflammatory, pain-relieving, and antipyretic properties. However, Ibuprofen is linked to specific well-known gastrointestinal adverse effects like ulceration and gastrointestinal bleeding. It has been linked to harmful effects on the liver, kidney, and heart. The purpose of the study is to create novel and potential IBU analogue with reduced side effects with the enhancement of their medicinal effects, so as to advance the overall safety profile of the drug. The addition of some novel functional groups including CH3, F, CF3, OCF3, Cl, and OH at various locations in its core structure suggestively boost the chemical as well as biological action. The properties of these newly designed structures were analyzed through chemical, physical, and spectral calculations using Density Functional Theory (DFT) and time-dependent DFT through B3LYP/6-31 g (d,p) basis set for geometry optimization. Molecular docking and non-bonding interaction studies were conducted by means of the human prostaglandin synthase protein (PDB ID: 5F19) to predict binding affinity, interaction patterns, and the stability of the protein-drug complex. Additionally, ADMET (Absorption, Distribution, Metabolism, Excretion, and Toxicity) and PASS (Prediction of Activity Spectra for Substances) predictions were employed to evaluate the pharmacokinetic and toxicological properties of these structures. Importantly, most of the analogues displayed reduced hepatotoxicity, nephrotoxicity, and carcinogenicity in comparison to the original drug. Moreover, molecular docking analyses indicated improved medicinal outcomes, which were further supported by pharmacokinetic calculations. Together, these findings suggest that the modified structures have reduced adverse effects along with improved therapeutic action compared to the parent drug.