Activity of Quercetin Derivatives as Antibacterial, Antioxidant and Anticancer Agents

Quercetin is a natural flavonoid known for its antioxidant, antibacterial, and anticancer activities, but its therapeutic application has been limited by its moderate potency, low bioavailability, and poor water solubility.  This study aimed to synthesize derivatives of quercetin with a view to enhancing its biological activity. Three Schiff base derivatives of quercetin (W1, W2, and W3) were synthesized by condensation with selected aniline derivatives. Their structures were verified by proton nuclear magnetic resonance )¹H-NMR), carbon-13 nuclear magnetic resonance (¹³C-NMR(, and Fourier-transform infrared (FT-IR) spectroscopy. Antibacterial activity was determined using agar well diffusion assay with cephalexin (30 mg/mL) used as the positive control. Antioxidant activity was assessed using the 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging assay. Cytotoxicity against HepG2 hepatocellular carcinoma cells was assessed by the methyl thiazolyl tetrazolium (MTT) assay. Antibacterial activity screening revealed inhibition zones of 17 mm against Staphylococcus aureus and Escherichia coli for quercetin, compared to 17/15 mm (W1), 15/14 mm (W2), and 13/12 mm (W3), while cephalexin produced inhibition zones of 20 mm and 25 mm against Staphylococcus aureus and Escherichia coli, respectively. Quercetin , W1 showed similar antioxidant activity, each with an IC₅₀ of 2.6 µg/mL, while W2 and W3 exhibited stronger antioxidant activity, with IC₅₀ values of 1.8 µg/mL and 1.6 µg/mL, respectively. Quercetin and its derivatives demonstrated strong and dose-dependent reductions in HepG2 cell viability, with IC₅₀ values of 185.8 µg/mL, 186.1 µg/mL, 213.7 µg/mL, and 244.3 µg/mL for quercetin, W1, W2, and W3, respectively. These results indicate that Schiff base derivatization enhances the antioxidant potential of quercetin while preserving comparable antibacterial and anticancer properties, positioning W1–W3 as potential lead compounds for future therapeutic development.