多靶点抗肿瘤天然产物研究进展

天然产物及其衍生物是抗肿瘤药物的重要组成部分。目前在临床上应用的天然产物来源的抗肿瘤药物以传统细胞毒类药物或靶向某一特定靶点的分子靶向药物为主,其应用受限于药物相关不良反应和肿瘤耐药。近年的研究表明,抗肿瘤活性天然产物往往能够靶向肿瘤细胞的多个靶点,影响肿瘤发生发展中的多个过程。由于肿瘤是一种多因素诱发的系统性疾病,多靶点天然产物在肿瘤治疗方面具有独特潜力。目前已发现的多靶点抗肿瘤天然产物的作用靶标和作用机制往往不够明确,限制了其进一步的开发。本文基于现代分子药理学理论,以多个典型的多靶点抗肿瘤天然产物为例进行综述,介绍了目前这些多靶点药物的作用机制、靶点确认和结构优化等研究进展,并对其作为抗肿瘤药物的研发前景进行了展望。

Research progress in multi-targeted anti-tumor natural products

Natural products and their derivatives are important components of anti-tumor drugs.Currently,anti-tumor drugs derived from natural products which are in clinical practice are mainly conventional cytotoxic or molecularly targeted drugs.Their application is limited by drug-related side effects and drug resistance.Recent studies have shown that anti-tumor natural products often act on multiple targets in tumor cells and in turn interfere with multiple processes in tumorigenesis and development.As tumor is a systemic disease induced by multiple factors,multi-targeted natural products possess unique potential in tumor therapy.However,the targets and mechanisms of the discovered multi-targeted antitumor natural products remain elusive,which limits their further development and application.This review summarized the research progress in the mechanism of action,target identification,and structure optimization of multi-targeted anti-tumor natural products exemplified by a few typical compounds.The research and development of these agents have also been proposed.