Metalloflavonoid strategy: enhancing quercetin efficacy through conjugation

Official URL: https://dx.doi.org/10.1530/REM-25-0024

Quercetin, one of nature’s most potent antioxidants, exhibits a broad spectrum of biological benefits, including anti-inflammatory, anti-cancer, anti-viral, and cardioprotective properties. However, the full therapeutic potential of this natural compound is partially restricted by fundamental physicochemical barriers, primarily low solubility and poor bioavailability. This review thoroughly investigates the potential of metal-ion-conjugated quercetin as a strategy to overcome these limitations and unlock its full efficacy. This review uniquely extends beyond quercetin’s established bioactivities to detail the specific therapeutic enhancements conferredbycomplexationwithdiversemetal ions. These complexes can significantly improve the solubility, thermal stability, and overall pharmacological properties of the parent compound. Conjugates formed with various metal ions – including iron, copper, zinc, cobalt, ruthenium, chromium, manganese, tin, and nickel – not only potentiate quercetin’s intrinsic antioxidant capacity but also introduce novel, enhanced properties that transcend non-conjugated quercetin. Extensive in vitro and in vivo studies confirm that metal complexation yields superior results, unlocking unique effects that surpass quercetin alone. Notably, their ability to modulate specific pathways, such as offering targeted antioxidant effects and exhibiting enhanced cellular penetration and bioavailability, positions these conjugates as a critical strategy for developing next-generation therapeutics. Such enhancements highlight the potential of these complexes in exhibiting improved anti-cancer, anti-microbial, neuroprotective, and anti-diabetic properties. In conclusion, quercetin–metal conjugates offer a means to enhance the compound’s preclinicalefficacy by precisely modulating its effects on oxidative stress and free radical formation. This possibility holds the potential to revolutionize the fields of personalized medicine and targeted therapy.