Hybrid Conjugates of Ibuprofen and 3,5‐Diarylidene‐4‐Piperidone: A New Avenue in Anti‐Inflammatory Drug Discovery

Nonsteroidal anti-inflammatory drugs (NSAIDs) have been crucial in managing inflammation, pain, and fever since their introduction in 1897. Despite their widespread use, NSAIDs often face limitations due to gastrointestinal side effects from the nonselective inhibition of cyclooxygenase (COX) isoenzymes, COX-1 and COX-2. While selective COX-2 inhibitors reduce gastrointestinal toxicity, they come with increased cardiovascular risks. This study investigates the synthesis and biological evaluation of novel hybrid NSAID conjugates incorporating 3,5-diarylidene-4-piperidinone, ibuprofen, and amino acids. These hybrid molecules are designed to enhance anti-inflammatory efficacy while minimizing adverse effects. The synthesized compounds are evaluated for COX inhibition and their effects on inflammatory mediators such as interleukin-6, tumor necrosis factor-alpha, and nitric oxide. Computational studies, including molecular docking and ADME (absorption, distribution, metabolism, and excretion) analyses, are performed to clarify the mechanisms of action and to predict pharmacokinetic properties. The findings indicate that some hybrid conjugates display promising anti-inflammatory properties, necessitating further investigation for their potential therapeutic applications.