Insights Into Chemical and Enzymatic Modifications of Naturally Occurring Flavonoids, Quercetin and Rutin: SAR and Bioactivity of the Derivatives

ABSTRACT Flavonoids are polyphenolic secondary plant metabolites found in a wide variety of fruits and vegetables and are known for their pharmacological benefits. Two of the most extensively studied flavonoids are quercetin and rutin, which exhibit a range of bioactivities, including anti‐cancer, anti‐microbial, anti‐inflammatory, anti‐diabetic, and neuroprotective effects. This review aims to summarize the beneficial effects of quercetin and its glycosylated form, rutin. Although there are challenges related to their solubility and bioavailability, chemical modifications of these flavonoids have helped address these limitations and improve their overall properties, making them effective in treating a broad range of pathological conditions and highlighting their clinical significance. For quercetin, chemical modifications include metal complexation, O‐substitutions, boronic acid derivatives, alkylthio methyl derivatives, pyrimidine derivatives, and other substitutions at the C3’ and C5 positions. In the case of rutin, modifications such as polyglucosylation, benzylation, enzymatic polymerization, hydrazine derivatives, aniline derivatives, and esterification are observed to enhance their therapeutic potential. Future research is necessary to explore further optimization that could enhance the pharmacokinetic and pharmacodynamic parameters, potentially leading to the development of more effective formulations.