College of Pharmacy, Gannan Medical University, Ganzhou 341000, PR China.
College of Pharmacy, Gannan Medical University, Ganzhou 341000, PR China.
Biomed Pharmacother. 2023 Feb;158:114190. doi: 10.1016/j.biopha.2022.114190. Epub 2023 Jan 4.
Securinega alkaloids are indolizidine alkaloids extracted from the leaf and root of an Asian plant, Securinega suffruticosa. Since its discovery in 1956 by Russian scientists, numerous studies have been conducted on securinega alkaloids and their derivatives as bioactive agents. In this review, published work on the bioactivities and the mechanism of action of securinega alkaloids and their derivatives is addressed. References were obtained through for example, the Web of Science, Science Direct, Pubmed and Google Scholar. Research into the synthesis of securinega alkaloids and their derivatives lacking activity assessment has been excluded. Comprehensive reviews show that securinega alkaloids and their derivatives exhibit a wide range of activities among which antineoplastic activity and nervous system related activity were reported although the mechanisms of action remain in part unknown. The other activities such as induction of differentiation, reversal of multi-drug resistance, cardiovascular system related activity, anti-inflammatory, adjuvant agent and anti-pathogenic activity are also reviewed. We found that modification at the C12, C14, and C15 sites on securinine improves the antitumor activity, while derivatives in which a bivalent mimetic is linked to the C15 site is beneficial for differentiation induction activity and reversal of P-glycoprotein mediated drug resistance. The most related pathways involved in the bioactivity of securinega alkaloids and their derivatives are JAK/STAT, PI3K/AKT/mTOR and MAPK. A perspective and expectation concerning the research of securinega alkaloids is presented at the end of this article. This review indicates directions around which constant endeavor could be valuable for researchers in the near future.
钩吻生物碱是从亚洲植物钩吻的叶和根中提取的吲哚里西啶生物碱。自 1956 年俄罗斯科学家发现以来，人们对钩吻生物碱及其衍生物作为生物活性物质进行了大量研究。在这篇综述中，讨论了钩吻生物碱及其衍生物的生物活性和作用机制的已发表研究。参考文献通过例如 Web of Science、Science Direct、Pubmed 和 Google Scholar 获得。排除了缺乏活性评估的钩吻生物碱及其衍生物的合成研究。综合评论表明，钩吻生物碱及其衍生物表现出广泛的活性，其中报道了抗肿瘤活性和神经系统相关活性，尽管作用机制在部分情况下仍不清楚。其他活性，如诱导分化、逆转多药耐药、心血管系统相关活性、抗炎、佐剂和抗病原体活性也进行了综述。我们发现，在 securinine 的 C12、C14 和 C15 位进行修饰可以提高抗肿瘤活性，而将双价模拟物连接到 C15 位的衍生物则有利于诱导分化活性和逆转 P-糖蛋白介导的耐药性。与钩吻生物碱及其衍生物的生物活性最相关的途径是 JAK/STAT、PI3K/AKT/mTOR 和 MAPK。本文最后提出了对钩吻生物碱研究的展望和期望。这篇综述为未来的研究人员指明了方向，这将是有价值的。
