Curcumin Derivatives and Its Analogues: A Comprehensive Review of Synthetic Advances, Structural Modifications and Biological Activities

Abstract

Curcumin, a naturally occurring polyphenolic compound derived from Curcuma longa, has attracted sustained scientific interest owing to its broad spectrum of pharmacological activities, including antimicrobial, antioxidant, anti-inflammatory, and anticancer effects. However, the clinical translation of native curcumin is severely limited by its poor chemical stability, low aqueous solubility, rapid metabolism, and weak bioavailability. To overcome these drawbacks, extensive efforts have been devoted to structural modification of the curcumin scaffold. This review provides a comprehensive overview of recent advances in the synthesis and design of curcumin derivatives and analogues, with particular emphasis on structural modification of the β-diketone moiety-especially the development of monocarbonyl curcumin analogues, as well as hybrid molecular structures. The review is structured using green and modern synthetic methodologies, including microwave-assisted, ultrasound-assisted, solvent-free, and ionic-liquid-mediated approaches. In addition, rational structural modification strategies, such as replacement of the β-diketone moiety, heterocyclic incorporation, and pharmacophore hybridization, are systematically analyzed. Reported studies demonstrate that these structural modifications significantly enhance stability and biological activities, with several derivatives exhibiting improved antibacterial, antifungal, anticancer, and antioxidant properties compared to native curcumin.