Fabaceae Flavonoids Beyond the Commonplace: A Review of Chemical Diversity, Pharmacological Activities, Mass Spectrometric Profiling and

Fabaceae family is recognized as a prolific flavonoid producer, including some unusual flavonoid skeletons. Although classic flavonoids have well-established biological properties in the literature, these unusual compounds remain underinvestigated. Based on that, the current study sought to explore the chemistry and biological activity of rare flavonoids in Fabaceae with a review comprising their occurrence, extraction, isolation and pharmacological potential. Additionally, the use of LC-MS applied to the study of seven subclasses (aurones, biflavonoids, coumestans, homoisoflavonoids, neoflavonoids, pterocarpans, and rotenoids) is also discussed. The review was carried out by searching for specified uniterms on SciFinder and Web of Science, covering the last ten years. In addition, to assess ADMET and drug-like properties by in silico predictions, all the substances considered in this work were compiled and organized into a curated dataset. As a result, a total of 170 flavonoid structures were included, most of which were found in the roots and leaves. In addition, a wide range of biological activities were observed, such as cytotoxic, antiviral and anti-inflammatory. Despite advancements in the use of LC-MS for bioprospection, just a few reports dedicated to the study of these compounds were found. Regarding ADMET profiles, most subclasses showed favorable bioavailability characteristics, with biflavonoids being the main exception. Together, this review highlights the significance of unusual flavonoids from the Fabaceae family, demonstrating their remarkable chemical diversity and largely, but still, unexplored pharmacological potential. These findings encourage further investigations, particularly in the fields of natural products chemistry, medicinal chemistry, and pharmacology.