Unlocking the potential of natural products: A comprehensive review of chrysin derivatives and their biological activities

Flavonoids are widely regarded as a versatile resource for the exploration and creation of anticancer substances. Chrysin, also known as 5,7-dihydroxy 2-phenyl-4 H -chromene-4-one or 5,7-dihydroxyfavone, is a naturally occurring flavonoid with a backbone made of 15 carbon atoms. This review explains chrysin’s chemistry, including its sources, synthesis, spectral data, and crystal structure, and reports the in vitro and in vivo activity, molecular docking, absorption, distribution, metabolism, and excretion (ADME) analysis, and structure-activity relationship (SAR) of chrysin derivatives. Despite the potential efficacy of chrysin in cancer treatment, some major challenges like low aqueous solubility, poor cellular uptake, physiochemical instability, rapid metabolism, and low oral bioavailability hinder its clinical use. There has been a significant focus on creating chrysin derivatives with a better ability to be absorbed by the body and exhibit stronger biological effects. The literature survey revealed that positions 2, 5, and 7 are the most studied in the structure, possessing diverse pharmacological activities. Of these, the 7 th substitution was most investigated. The various substitutions with different linkages like ester, ether, acetamide, acetohydrazide, phosphate, etc. have produced antibacterial to anticancer activity. The chrysin metal complexes have been shown to increase the oral bioavailability, solubility, and stability. The nano-formulation approach of chrysin led to advantages like targeted delivery, improved solubility, and bioavailability.