Structural Modifications of Curcumin toward Clinical Applications

Curcumin has attracted significant attention for its therapeutic potential across a range of diseases, including cancer, inflammation, and neurodegenerative disorders. However, its clinical efficacy is limited by poor bioavailability, instability under physiological conditions, and a lack of specificity. This review explores chemical strategies to address these limitations, focusing on enhancing curcumin’s bioavailability, metabolic stability, and target specificity, particularly against DYRK-2. It examines diverse structural modifications of curcumin, including reducing the diketo group to a monoketo form, substituting the diketo group with heterocyclic rings, and other targeted modifications aimed at overcoming curcumin's pharmacokinetic challenges. Recent advancements, including the development of curcumin analogues with improved pharmacokinetic profiles, are highlighted, alongside an evaluation of their impact on bioactivity and therapeutic efficacy. Additionally, persistent challenges, such as toxicity, selectivity, and reactivity with biomolecules like glutathione, are identified. By incorporating current findings and future directions, this review highlights the need for continued innovation in curcumin analogue development to realise its clinical potential.