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Flavonoids and Their Synthetic Derivatives, Chemistry and Biological Applications - A Review

ADEWOLE Esther Abisola ALIMI Ayomide Basit AGBONIFO Etinosa OMOYELE Faith Princess IKECHUKWU Uche Godwin ABONYI Stanley Arinze KAYODE Esther Abiola

Subject area: Physical Sciences and Environment  ·  Area of research: Organic Chemistry

DOI: https://doi.org/10.64388/IREV9I3-1710424-1486

Abstract

The emergence of drug-resistant microbes has created an urgent need for new antimicrobial agents. Flavonoids, a diverse group of polyphenolic plant metabolites, have shown great promise in this regard due to their wide range of biological activities. While naturally occurring, flavonoids are the most extensively studied, semi-synthetic and synthetic flavonoid derivatives have demonstrated remarkable antimicrobial potential, often inhibiting or killing microbes at concentrations below 1 ?g mL??. Their substitution patterns frequently include hydroxyl groups, halogens, or heteroatomic rings such as pyridine, piperidine, or 1,3-dithiolium cations, though the diversity of substituents, this complicates the establishment of clear structure?activity relationships. First isolated in 1930 from oranges and initially misclassified as vitamin P, flavonoids are now recognized as key plant secondary metabolites, with over 10,000 identified to date. They are abundant in fruits, grains, vegetables, tea, and wine, and have found applications across nutraceutical, medicinal, cosmetic, and pharmaceutical industries. The broad utilization of flavonoids can be attributed to their antioxidant, anti-inflammatory, antimutagenic, and anticancer properties, as well as their ability to modulate cellular enzyme functions. Chemically, flavonoids are hydroxylated phenolic compounds synthesized by plants in response to microbial infection, and their activity is strongly influenced by structural class, degree of hydroxylation, substitution, conjugation, and polymerization. Based on chemical structure, flavonoids are classified into six subclasses: flavonols, flavones, flavanols, flavanones, isoflavones, and anthocyanins, each with distinct biological profiles. This review highlights the chemistry and biological applications of flavonoids and their synthetic derivatives, emphasizing their potential as novel antimicrobial agents in the fight against drug-resistant pathogens.

Keywords

Flavonoids; Synthetic derivatives, antimicrobial agents, Drug resistance, Polyphenolic compounds, Antioxidant activity, Nutraceuticals.

References

[1] Agati, G., & Tattini, M. (2010). Multiple functional roles of flavonoids in photoprotection. New Phytologist, 186(4), 786–793.

[2] Agati, G., Azzarello, E., Pollastri, S., & Tattini, M. (2012). Flavonoids as antioxidants in plants: Location and functional significance. Plant Science, 196, 67–76.

[3] Bors, W., Heller, W., Michel, C., & Saran, M. (1990). Flavonoids as antioxidants: Determination of radical-scavenging efficiencies. Methods in Enzymology, 186, 343–355.

[4] Brahmachari, G. (2008). Naturally occurring flavanones: An overview. Natural Product Communications, 3, 1934578X0800300820.

[5] Chávez-González, M. L., Sepúlveda, L., Verma, D. K., Luna-García, H. A., Rodríguez-Durán, L. V., Ilina, A., & Aguilar, C. N. (2020). Conventional and emerging extraction processes of flavonoids. Processes, 8, 434.

[6] Clifford, M. N., & Cuppett, S. L. (2000). [Check if you want this formally included].

[7] Dias, M. C., Pinto, D. C. G. A., & Silva, A. M. S. (2021). Plant flavonoids: Chemical characteristics and biological activity. Molecules, 26, 5377.

[8] Erlejman, A. G., Verstraeten, S. V., Fraga, C. G., & Oteiza, P. I. (2004). The interaction of flavonoids with membranes: Potential determinant of flavonoid antioxidant effects. Free Radical Research, 38(12), 1311–1320.

[9] Ferdinando, M. D., Brunetti, C., Fini, A., & Tattini, M. (2012). Flavonoids as antioxidants in plants under abiotic stresses. In P. Ahmad & M. N. V. Prasad (Eds.), Abiotic Stress Responses in Plants: Metabolism, Productivity and Sustainability (pp. 159–179). Springer.

[10] Harborne, J. B., & Williams, C. A. (2000). Advances in flavonoid research since 1992. Phytochemistry, 55(6), 481–504.

[11] Hatier, J. H. B., & Gould, K. S. (2008). Foliar anthocyanins as modulators of stress signals. Journal of Theoretical Biology, 253(3), 625–627.

[12] Heim, K. E., Tagliaferro, A. R., & Bobilya, D. J. (2002). Flavonoid antioxidants: Chemistry, metabolism and structure–activity relationships. The Journal of Nutritional Biochemistry, 13(10), 572–584.

[13] Jansen, M. A. K. (2002). Ultraviolet-B radiation effects on plants: Induction of morphogenic responses. Physiologia Plantarum, 116(3), 423–429.

[14] Kuhn, B. H., Geisler, M., Bigler, L., & Ringli, C. (2011). Flavonols accumulate asymmetrically and affect auxin transport in Arabidopsis. Plant Physiology, 156(2), 585–595.

[15] Kumar, S., & Pandey, A. K. (2013). Chemistry and biological activities of flavonoids: An overview. The Scientific World Journal, 2013, 162750.

[16] Liga, S., Paul, C., & Péter, F. (2023). Flavonoids: Overview of biosynthesis, biological activity, and current extraction techniques. Plants, 12(14), 2732. https://doi.org/10.3390/plants12142732

[17] Manach, C., Scalbert, A., Morand, C., Rémésy, C., & Jiménez, L. (2004). Polyphenols: Food sources and bioavailability. The American Journal of Clinical Nutrition, 79(5), 727–747.

[18] Markham, K. R. (1982). Techniques of Flavonoid Identification. Academic Press.

[19] Mathesius, U. (2001). Flavonoids induced in cells undergoing nodule organogenesis in white clover are regulators of auxin breakdown by peroxidase. Journal of Experimental Botany, 52, 419–426.

[20] Mukherjee, P. K. (2019). Chapter 7—Bioactive phytocomponents and their analysis. In Quality Control and Evaluation of Herbal Drugs (pp. 237–328). Elsevier.

[21] Mullineaux, P. M., & Karpinski, S. (2002). Signal transduction in response to excess light: Getting out of the chloroplast. Current Opinion in Plant Biology, 5(1), 43–48.

[22] Nabavi, S. M., Šamec, D., Tomczyk, M., Milella, L., Russo, D., Habtemariam, S., Suntar, I., Rastrelli, L., Daglia, M., & Xiao, J. (2020). Flavonoid biosynthetic pathways in plants: Versatile targets for metabolic engineering. Biotechnology Advances, 38, 107316.

[23] Naoumkina, M., & Dixon, R. A. (2008). Subcellular localization of flavonoid natural products. Plant Signaling & Behavior, 3(8), 573–575.

[24] Okoye, C. O., Jiang, H., Wu, Y., Li, X., Gao, L., Wang, Y., & Jiang, J. (2023). Bacterial biosynthesis of flavonoids: Overview, current biotechnology applications, challenges, and prospects. Journal of Cellular Physiology. (Early view).

[25] Panche, A. N., Diwan, A. D., & Chandra, S. R. (2016). Flavonoids: An overview. Journal of Nutritional Science, 5, e47.

[26] Pérez-Gregorio, M. R., Regueiro, J., Barreiro, C. G., Otero, R. R., & Gándara, J. S. (2011). Changes in antioxidant flavonoids during freeze-drying of red onions and subsequent storage. Food Control, 22(7), 1108–1113.

[27] Pietta, P. G. (2000). Flavonoids as antioxidants. Journal of Natural Products, 63(7), 1035–1042.

[28] Pietta, P., Minoggio, M., & Bramati, L. (2003). Plant polyphenols: Structure, occurrence and bioactivity. In A.-U. Rahman (Ed.), Studies in Natural Products Chemistry (Vol. 28, pp. 257–312). Elsevier.

[29] Rehan, M. (2021). Biosynthesis of diverse class flavonoids via shikimate and phenylpropanoid pathway. In L. Q. Zepka, T. C. D. Nascimento, & E. Jacob-Lopes (Eds.), Bioactive Compounds (Ch. 6). IntechOpen.

[30] Rice-Evans, C. A., Miller, N. J., & Paganga, G. (1996). Structure–antioxidant activity relationships of flavonoids and phenolic acids. Free Radical Biology and Medicine, 20(7), 933–956.

[31] Saslowsky, D. E., Warek, U., & Winkel, B. S. J. (2005). Nuclear localization of flavonoid enzymes in Arabidopsis. Journal of Biological Chemistry, 280(25), 23735–23740.

[32] Shirley, B. W. (1996). Flavonoid biosynthesis: “New” functions for an “old” pathway. Trends in Plant Science, 1(11), 377–382.

[33] Tariq, H., Asif, S., Andleeb, A., Hano, C., & Abbasi, B. H. (2023). Flavonoid production: Current trends in plant metabolic engineering and de novo microbial production. Metabolites, 13, 124.

[34] Tattini, M., Galardi, C., Pinelli, P., Massai, R., Remorini, D., & Agati, G. (2004). Differential accumulation of flavonoids and hydroxycinnamates in leaves of Ligustrum vulgare under excess light and drought stress. New Phytologist, 163(3), 547–561.

[35] Taylor, L. P., & Grotewold, E. (2005). Flavonoids as developmental regulators. Current Opinion in Plant Biology, 8(3), 317–323.

[36] Tzanova, M., Atanasov, V., Yaneva, Z., Ivanova, D., & Dinev, T. (2020). Selectivity of current extraction techniques for flavonoids from plant materials. Processes, 8, 1222.

[37] Wang, Y., Chen, S., & Yu, O. (2011). Metabolic engineering of flavonoids in plants and microorganisms. Applied Microbiology and Biotechnology, 91(4), 949–956.

[38] Yao, L. H., Jiang, Y. M., Shi, J., Tomás-Barberán, F. A., Datta, N., Singanusong, R., & Chen, S. S. (2004). Flavonoids in food and their health benefits. Plant Foods for Human Nutrition, 59(3), 113–122.

[39] Zandi, K., Teoh, B. T., Sam, S. S., Wong, P. F., Mustafa, M. R., & Abubakar, S. (2011). Antiviral activity of four types of bioflavonoid against dengue virus type-2. Virology Journal, 8, 560.

[40] Zhao, J., & Dixon, R. A. (2010). The “ins” and “outs” of flavonoid transport. Trends in Plant Science, 15(2), 72–80.

How to cite this paper

ADEWOLE Esther Abisola, ALIMI Ayomide Basit, AGBONIFO Etinosa, OMOYELE Faith Princess; IKECHUKWU Uche Godwin, ABONYI Stanley Arinze; KAYODE Esther Abiola "Flavonoids and Their Synthetic Derivatives, Chemistry and Biological Applications - A Review" Iconic Research And Engineering Journals Volume 9 Issue 3 2025 Page 130-138 https://doi.org/10.64388/IREV9I3-1710424-1486
ADEWOLE Esther Abisola, ALIMI Ayomide Basit, AGBONIFO Etinosa, OMOYELE Faith Princess; IKECHUKWU Uche Godwin, ABONYI Stanley Arinze; KAYODE Esther Abiola "Flavonoids and Their Synthetic Derivatives, Chemistry and Biological Applications - A Review" Iconic Research And Engineering Journals, vol. 9, no. 3, Sep. 2025, doi: https://doi.org/10.64388/IREV9I3-1710424-1486
ADEWOLE Esther Abisola, ALIMI Ayomide Basit, AGBONIFO Etinosa, OMOYELE Faith Princess; IKECHUKWU Uche Godwin, ABONYI Stanley Arinze; KAYODE Esther Abiola (2025). Flavonoids and Their Synthetic Derivatives, Chemistry and Biological Applications - A Review. Iconic Research And Engineering Journals, 9(3). doi: https://doi.org/10.64388/IREV9I3-1710424-1486
ADEWOLE Esther Abisola, ALIMI Ayomide Basit, AGBONIFO Etinosa, OMOYELE Faith Princess; IKECHUKWU Uche Godwin, ABONYI Stanley Arinze; KAYODE Esther Abiola "Flavonoids and Their Synthetic Derivatives, Chemistry and Biological Applications - A Review" Iconic Research And Engineering Journals, vol. 9, no. 3, Sep. 2025. Crossref, https://doi.org/10.64388/IREV9I3-1710424-1486
@article{1710424,
      author = {ADEWOLE Esther Abisola, ALIMI Ayomide Basit, AGBONIFO Etinosa, OMOYELE Faith Princess; IKECHUKWU Uche Godwin, ABONYI Stanley Arinze; KAYODE Esther Abiola},
      title = {Flavonoids and Their Synthetic Derivatives, Chemistry and Biological Applications - A Review},
      journal = {Iconic Research And Engineering Journals},
      year = {2025},
      volume = {9},
      number = {3},
      pages = {130-138},
      issn = {2456-8880},
      url = {https://www.irejournals.com/formatedpaper/1710424.pdf},
      abstract = {The emergence of drug-resistant microbes has created an urgent need for new antimicrobial agents. Flavonoids, a diverse group of polyphenolic plant metabolites, have shown great promise in this regard due to their wide range of biological activities. While naturally occurring, flavonoids are the most extensively studied, semi-synthetic and synthetic flavonoid derivatives have demonstrated remarkable antimicrobial potential, often inhibiting or killing microbes at concentrations below 1 ?g mL??. Their substitution patterns frequently include hydroxyl groups, halogens, or heteroatomic rings such as pyridine, piperidine, or 1,3-dithiolium cations, though the diversity of substituents, this complicates the establishment of clear structure?activity relationships. First isolated in 1930 from oranges and initially misclassified as vitamin P, flavonoids are now recognized as key plant secondary metabolites, with over 10,000 identified to date. They are abundant in fruits, grains, vegetables, tea, and wine, and have found applications across nutraceutical, medicinal, cosmetic, and pharmaceutical industries. The broad utilization of flavonoids can be attributed to their antioxidant, anti-inflammatory, antimutagenic, and anticancer properties, as well as their ability to modulate cellular enzyme functions. Chemically, flavonoids are hydroxylated phenolic compounds synthesized by plants in response to microbial infection, and their activity is strongly influenced by structural class, degree of hydroxylation, substitution, conjugation, and polymerization. Based on chemical structure, flavonoids are classified into six subclasses: flavonols, flavones, flavanols, flavanones, isoflavones, and anthocyanins, each with distinct biological profiles. This review highlights the chemistry and biological applications of flavonoids and their synthetic derivatives, emphasizing their potential as novel antimicrobial agents in the fight against drug-resistant pathogens.},
      keywords = {Flavonoids; Synthetic derivatives, antimicrobial agents, Drug resistance, Polyphenolic compounds, Antioxidant activity, Nutraceuticals.},
      month = {September},
      doi = {https://doi.org/10.64388/IREV9I3-1710424-1486}
  }