Breast cancer is one of the most prevalent malignancies in women worldwide, with challenging treatment. A large number of breast cancer cases are estrogen-dependent; thus, aromatase, which plays a central role in estrogen synthesis, is a key target for therapeutic strategies. Several aromatase inhibitors are currently used in clinical practice. Plants are rich sources of various compounds with valuable biological activities, including flavonoids. Flavonoids are a diverse group of phytoconstituents exhibiting aromatase-inhibitory properties. Among the flavonoid subclasses, flavanones exhibit a pronounced ability to inhibit aromatase; however, their natural distribution is limited, with citrus fruits as the richest sources. This study reviews the characteristics of aromatase, its role in breast cancer, the application of aromatase inhibitors in treatment, and the mechanisms underlying drug resistance. It also examines flavonoids and their subclasses, along with the flavonoid content of citrus fruits, with an emphasis on flavanone composition and anti-aromatase activity. Molecular docking simulations and virtual pharmacokinetic evaluations were conducted to assess the binding affinities and interactions between citrus flavanones and aromatase, and to compare their ADME properties. The findings from in silico analyses suggest that pinocembrin, a flavanone aglycone, could be a candidate for further examination of its anti-aromatase activity. Nevertheless, further studies are required to substantiate the effectiveness of pinocembrin.
Bahman Nickavar (Wed,) studied this question.