School of Chinese Materia Medica, Tianjin University of Traditional Chinese Medicine, Tianjin, 301617, China.
Med Chem. 2023;19(9):823-837. doi: 10.2174/1573406419666230403120956.
Berberine (BBR) is a quaternary ammonium alkaloid isolated from the Traditional Chinese Medicine . 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.
小檗碱（BBR）是从中药中分离得到的一种季铵型生物碱。由于其独特的结构特性，使其易于通过π-π堆积和静电相互作用与大分子相互作用，因此具有丰富的药理活性。近年来，其抗肿瘤作用越来越受到关注。细胞毒性和抗增殖是 BBR 的重要抗肿瘤模式，许多研究小组对此进行了研究。本研究旨在综述 BBR 及其细胞毒性衍生物的结构修饰，并研究相应的构效关系。BBR 对肿瘤细胞表现出潜在的活性，但其活性适中且理化性质较差，阻碍了其在临床上的应用。结构修饰是提高 BBR 细胞毒性或抗增殖活性的常用有效方法。综述总结了 BBR 的结构修饰、其衍生物的细胞毒性或抗增殖活性以及相应的构效关系（SAR）。BBR 衍生物的 SAR 及其细胞毒性或抗增殖活性将为以 BBR 为先导化合物的抗肿瘤药物设计提供广阔的前景。
