Activity of Quercetin Derivatives as Antibacterial, Antioxidant and Anticancer Agents
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Abstract
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.
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References
Chen S, Wang X, Cheng Y, Gao H, Chen X. A review of classification, biosynthesis, biological activities and potential applications of flavonoids. Molecules. 2023; 28(2):215-229.
Xu SL, Zhu KY, Bi CWC, Yan L, Men SWX, Dong TTX, Tsim KW. Flavonoids derived from traditional Chinese medicines show roles in neuronal differentiation: possible targets in developing health food products. Birth Defects Res C Embryo Today. 2013; 99(2):79-94.
Hassanpour SH and Doroudi A. Antioxidant potential of flavonoids as polyphenolic compounds and substitutes for synthetic antioxidants. Avicenna J Phytomed. 2023; 13(1):1-15.
Lim H, Heo MY, Kim HP. Flavonoids as broad spectrum agents against chronic inflammation. Biomol Ther (Seoul). 2019; 27(5):435-445.
Kopustinskiene DM, Jakstas V, Savickas A, Bernatoniene J. Flavonoids as anticancer agents. Nutrients. 2020; 12(2):457-466.
Khan J, Deb PK, Priya S, Medina KD, Devi R, Walode SG. Dietary flavonoids: cardioprotective potential with antioxidant effects and pharmacokinetic considerations. Molecules. 2021; 26(7):2075-2094.
Al-Oudah GA, Ewad RM, Hadi BH, Al Temimi TA, Shlash AM, Lo HY, Hindi KN, Jasim HM, Jaafer LA, Almansori AK. Integrative in vitro and in silico analysis of Origanum majorana flavonoids: targeting β-lactamase and penicillin-binding proteins through conserved region-based structural optimization. Trop J Nat Prod Res. 2025; 9(6):2664-2672.
Mirza MA, Mahmood S, Hilles AR, Ali A, Khan MZ, Zaidi SAA, Iqbal Z, Ge Y. Quercetin as a therapeutic product: pharmacological action and clinical applications – a review. Pharmaceuticals. 2023; 16(1):55-67.
Falodun A, Okafor OI, Eriyamremu O, Okugbo OT. Phytochemical investigation and antioxidant activity evaluation of Pyrenacantha staudtii (Icacinaceae) leaf. Trop J Phytochem Pharm Sci. 2025; 4(6):255-259.
Yang D, Wang T, Long M, Li P. Quercetin: pharmacological activity and clinical applications. Oxid Med Cell Longev. 2020; 2020:882-893.
Purwanti T, Hendradi E, Amalia SN, Arum FS, Hariyadi DM. Characterization and penetration of quercetin spanlastic gel with Span 60 as vesicle builder and edge activator of Brij 35 and Tween 60. Trop J Nat Prod Res. 2025; 9(6):2750-2754.
Shen P, Lin W, Deng X, Ba X, Han L, Chen Z, Qin K, Huang Y, Tu S. Potential Implications of quercetin in autoimmune diseases. Front Immunol. 2021; 12:679044.
Wang Y, Tao B, Wan Y, Sun Y, Wang L, Sun J, Li C. Drug delivery-based enhancement of quercetin pharmacology and therapeutic potential against oral diseases. Biomed Pharmacother. 2020; 132:110882.
Okeke AP and Adeniyi DB. Maternal high-fat diet and quercetin supplementation during lactation influences ovarian follicular development in female Wistar rat offspring. Trop J Nat Prod Res. 2025; 9(6):2880-2885.
Xu D, Hu MJ, Wang YQ, Cui YL. Antioxidant activities of quercetin and its complexes for medicinal applications. Molecules. 2019; 24(6):1123-1138.
Ghamari Kargar P, Moodi Z, Bagherzade G, Nikoomanesh F. Synthesis, characterization, and antimicrobial activity of metal complexes derived from Schiff base of quercetin from Origanum vulgare L. Mater Chem Phys. 2024; 303:127748.
Bui TA, Do MT, Do STT, Nguyen TT, Duong CD. Simultaneous analysis method for rutin, diosmin, hesperidin, and quercetin in solid food supplements by HPLC-PDA. Trop J Nat Prod Res. 2025; 9(2):473-479.
Zhang J, Huan RH, Han YQ. Quercetin exhibits anti-leukemia effects via regulation of metabolic reprogramming. HemaSphere. 2023; 7(Suppl 2):PB1829.
Okolie NP, Falodun A, Oluseyi D. Evaluation of the antioxidant activity of root extract of pepper fruit (Dennettia tripetala) and its potential to inhibit lipid peroxidation. Afr J Tradit Complement Altern Med. 2014; 11(3):221-227.
Falodun A, Siraj R, Choudhary MI. GC-MS insecticidal leaf essential oil of P. staudtii Hutch & Dalz (Icacinaceae). Trop J Pharm Res. 2009; 8(2):139-143.
Karak P. Biological activities of flavonoids: An overview. Int J Pharm Sci Res. 2019; 10(4):1567-1574.
Vanden Berghe DA and Vlietinck AJ. Screening methods for antibacterial and antiviral agents from higher plants. In: Dey PM, Harborne JB, editors. Methods in Plant Biochemistry. London: Academic Press; 1991. p. 47–69.
Tjandra L, Setyawan B, Masfufatun M. Characteristics of Indonesian wild honey and cultivated honey and their antibacterial activity against Staphylococcus aureus and Escherichia coli. J Ilm Kedokt Wijaya Kusuma. 2022; 11(2):45–52.
Brand-Williams W, Cuvelier ME, Berset C. Use of a free radical method to evaluate antioxidant activity. LWT – Food Sci Technol. 1995; 28(1):25–30.
Mosmann T. Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J Immunol Methods. 1983; 65(1–2):55–63.
Kumar S and Pandey AK. Chemistry and biological activities of flavonoids: an overview. Sci World J. 2013:1–16.
Dajas F. Life or death: neuroprotective and anticancer effects of quercetin. J Ethnopharmacol. 2012; 143(2):383-396.
Liu T, Li Z, Tian F. Quercetin inhibited the proliferation and invasion of hepatoblastoma cells through facilitating SIRT6-mediated FZD4 silence. Hum Exp Toxicol. 2021; 40(7):1234–42.
Guan H, Zhang W, Liu H, Jiang Y, Li F, Wu M, Waterhouse GIN, Sun-Waterhouse D, Li D. Quercetin induces apoptosis in HepG2 cells via directly interacting with YY1 to disrupt YY1–p53 interaction. Metabolites. 2023; 13(2):229.
Sethi G, Rath P, Chauhan A, Ranjan A, Choudhary R, Ramniwas S, Sak K, Aggarwal D, Rani I, Tuli HS. Apoptotic mechanisms of quercetin in liver cancer: recent trends and advancements. Pharmaceutics. 2023; 15(2):712.
Aslani F, Afarin R, Madiseh ND, Nasab HB, Monjezi S, Igder S, et al. Potentiation of apoptotic effect of combination of etoposide and quercetin on HepG2 liver cancer cells. Hepat Mon. 2023; 23(3):e12753.
Abbas Z, Kumar M, Tuli HS, Janahi EM, Haque S, Harakeh S, Dhama K, Aggarwal P, Varol M, Rani A, Sharma S. Synthesis, structural investigations, and in vitro/in silico bioactivities of flavonoid-substituted biguanide: A novel Schiff base and its diorganotin(IV) complexes. Molecules. 2022; 27(24):8874.
Gori T, Di Stolfo G, Sicuro S. Oxidative stress and free radicals in disease pathogenesis: A review. Trop J Pharm Res. 2020;19(6):1234–1244.
Liu L, Wei S, Wang S, Zhang Z, Li Y. Synthesis and biological evaluation of acetylated derivatives of quercetin with enhanced antioxidant activity. Trop J Pharm Res. 2021; 20(9):1995–2004.
Rice-Evans CA, Miller NJ, Paganga G. Structure-antioxidant activity relationships of flavonoids and phenolic acids. Free Radic Biol Med. 1996; 20:933–956.
Taheri E, Mahdavi M, Dehghan G, Vaziri B, Heydari A. Novel Schiff base derivatives of quercetin: synthesis, characterization and cytotoxic activity. Trop J Pharm Res. 2023; 22(3):617–624.