基于抗肿瘤作用的苦参碱结构修饰及构效关系的研究进展

Advances in structure modification and structure-activity relationship of matrine based on antitumor effect

目的 总结苦参碱的抗肿瘤机制以及苦参碱衍生物在抗肿瘤中的构效关系,为苦参碱的开发提供进一步的科学依据。方法 以“苦参碱”“衍生物”“肿瘤”和“药理活性”等为关键词,收集中国知网、万方、维普、PubMed和Science Direct等数据库中的相关报道,并进行总结和挖掘。结果 苦参碱是中药苦参的主要活性成分,在消化系统肿瘤、呼吸系统肿瘤、妇科肿瘤、白血病、前列腺癌等多种恶性肿瘤的治疗中具有较好的药理活性。通过诱导肿瘤细胞分化,引起程序性细胞死亡、抑制肿瘤细胞的侵袭和转移、逆转肿瘤细胞的多药耐药性、干扰肿瘤细胞的生长周期以及抑制肿瘤细胞的端粒酶活性等方式发挥其抗肿瘤作用。苦参碱结构修饰主要集中于母环上的13,14,15及16位。结论 苦参碱对多种类型的肿瘤具有良好的药理活性,结构改造可以弥补苦参碱本身的某些不足,为苦参碱的开发提供进一步的信息依据。

Objective To review matrine’s anti-tumor mechanism and the structure-activity connection of its derivatives in anti-tumor treatment,as well as to give more scientific support for matrine development.Methods By using keywords such as“matrine”,“derivative”,“tumor”,and“pharmacological activity”,the associated studies in the CNKI,Wanfang,Weipu,PubMed,and Science Direct databases were gathered and summarized.Results Matrine is a primary active component of Sophora flavescens,which has demonstrated significant pharmacological action in digestive system malignancies,respiratory system tumors,gynecological tumors,leukemia,prostate cancer,and other malignant tumors.Its anticancer action is achieved by inducing tumor cell differentiation,causing programmed cell death,reducing tumor cell invasion and metastasis,reversing tumor cell multidrug resistance,interfering with tumor cell development cycle,and decreasing tumor cell telomerase activity.The alteration of matrine focuses mostly on the parent ring locations 13,14,15,and 16.Conclusion Matrine has strong pharmacological action against several types of cancers,and structural alteration can compensate for some of matrine’s weaknesses,providing more information for matrine development.