Zinc(II) Complexation Enhances the Antidiabetic and Antioxidant Properties of Cinnamic Acid

This study aimed to develop a novel zinc–cinnamic acid nutraceutical with enhanced and multimodal antidiabetic and antioxidant properties. A Zn(II) acetate complex of cinnamic acid was synthesized and characterized using FT-IR and ^1H NMR spectroscopy. Cytotoxicity was evaluated. Antioxidant activity was assessed using DPPH and ABTS radical-scavenging and Fe^3+-reducing assays. Antiglycation activity and inhibitory effects against α-glucosidase and α-amylase were also evaluated. The insulin-mimetic activity of the complex was assessed based on glucose uptake in differentiated L6 myotubes. Molecular docking was subsequently performed against GLUT4 and protein kinase B (PKB/Akt). FT-IR and ^1H NMR analyses indicated that Zn(II) coordinated with cinnamic acid through an oxygen-based coordination mode, forming a complex containing two cinnamic acid ligands. Zn(II) complexation significantly enhanced the antiglycation activity of cinnamic acid (p < 0.05), reducing its IC_50 from 29.3 to 13.9 μM (approximately 2.1-fold enhancement). Notably, complexation conferred pronounced glucose uptake activity (EC_50 = 31 μM) and α-glucosidase inhibitory activity (IC_50 = 59.4 μM) on cinnamic acid, with the complex exhibiting approximately 162- and 2.1-fold greater activities, respectively, than the parent compound (p < 0.05). Molecular docking further demonstrated stronger interactions of the Zn(II)–cinnamic acid complex with GLUT4 and PKB/Akt than with cinnamic acid alone. Importantly, the complex exhibited no marked cytotoxicity at the concentrations evaluated. The findings demonstrate a structure–activity relationship in which Zn(II) complexation substantially enhances the antidiabetic and antiglycation properties of cinnamic acid. The resulting complex exhibited multifunctional pharmacological activities, including enhanced glucose uptake, α-glucosidase inhibition and antiglycation activity, while maintaining a favourable cytotoxicity profile. These findings support further investigation of the Zn(II)–cinnamic acid complex as a potential nutraceutical candidate for glycaemic management and the prevention of diabetes-associated glycation-related complications.