Insight on Structural Modification, Cytotoxic or Anti-Proliferative Activity, Structure-Activity Relationship of Berberine Derivatives

Berberine (BBR) is a quaternary ammonium alkaloid isolated from the Traditional Chinese Medicine Coptis chinensis. It possesses a plethora of pharmacological activities because its unique structure properties make it readily interact with macromolecules through π-π stacking and electrostatic interaction. Its anti-tumor effects are receiving more and more attention in recent years. Cytotoxicity and anti-proliferation are the important anti-tumor modes of BBR, which have been studied by many research groups. This study aims to review the structural modifications of BBR and its cytotoxic derivatives. Also, to study the corresponding structure-activity relationship. BBR showed potential activities toward tumor cells, however, its modest activity and poor physicochemical properties hindered its application in clinical. Structural modification is a common and effective approach to improve BBR's cytotoxic or anti-proliferative activities. The structural modifications of BBR, the cytotoxic or anti-proliferative activities of its derivatives, and the corresponding structure-activity relationship (SAR) were summarized in the review. The concluded SAR of BBR derivatives with their cytotoxic or anti-proliferative activities will provide great prospects for the future anti-tumor drug design with BBR as the lead compound.