Cinnamic Acid-based Hybrid Molecules as Multitarget Therapeutic Agents for Cancer, Alzheimer's Disease, and Malaria: A Review.

Molecular hybridization has emerged as a powerful medicinal chemistry approach for address the limitations of conventional single-target therapeutics, particularly in the treatment of complex, multifactorial diseases. This strategy involves integrating two or more pharmacologically active pharmacophores into a single molecular framework, enabling enhanced biological activity, multi-target interactions, and improved pharmacokinetic properties. Among the diverse scaffolds investigated for hybrid drug design, cinnamic acid has attracted considerable attention owing to its structural simplicity, synthetic accessibility, and broad spectrum of biological activities. The incorporation of cinnamic acid into hybrid molecules has generated a wide range of compounds with improved therapeutic potential and selectivity. The pharmacological effects of cinnamic acid hybrids are associated with the modulation of key enzymes, including α-glucosidase, α-amylase, and acetylcholinesterase, as well as important signaling pathways such as NF-κB, COX-2, iNOS, PI3K/Akt/mTOR, and MAPK/ERK. These molecular interactions contribute to their diverse biological activities and therapeutic applications. This review provides a comprehensive overview of recent developments in cinnamic acid-based molecular hybrids, emphasizing design strategies, structure- activity relationships, pharmacological properties, and underlying mechanisms of action. Particular attention is given to their anticancer, neuroprotective, and antimalarial therapeutic applications. Furthermore, the review critically examines the advantages and current challenges of cinnamic acid hybridization and highlights future research directions. Overall, cinnamic acid-based molecular hybrids represent a promising platform for the development of multifunctional therapeutic agents with enhanced efficacy and broader clinical potential.