Estrogenic actions of alkaloids: Structural characteristics and molecular mechanisms

[Display omitted] This comprehensive review of estrogenic alkaloids reveals that although the number is small, they exhibit a wide range of structures, biosynthesis pathways, mechanisms of action, and applications. Estrogenic alkaloids belong to different classes, different biosynthetic pathways, different estrogenic actions (estrogenic/synergistic, anti-estrogenic/antagonistic, biphasic, and acting as a selective estrogen receptor modulator or SERM), different receptor-initiated signaling pathways, different ways of modulations of estrogen action, and different applications. The future applications of estrogenic alkaloids, such as those for diagnostics, drug development, and therapeutics, are considered with the help of new databases containing comprehensive descriptions of their relationships and more elaborate artificial intelligence-based prediction technologies. Structure-activity studies reveal the significance of the nitrogen atom for their structural and functional diversity, which may help support their broader applications. Based on the summary of previous reports, estrogenic alkaloids have significant potential for future applications.