Background: Multidrug resistance (MDR) is the resistance of cancer cells against a variety of currently used antineoplastic agents with diverse structural scaffolds and different anticancer mechanisms. It has been recognized as one of the major impediments to the successful treatment of cancer, leading to the metastasis and relapse of malignant diseases.

Introduction: Collateral sensitivity (CS) is the characteristic of certain chemicals to kill the drugresistant sublines selectively over the parental cell lines from which the resistant cells were generated. The research and development of new drug candidates with collateral sensitivity will be an efficient approach to conquer multidrug resistance in cancer. We aim to provide an update on the discovery of natural products with collateral sensitivity.

Results and Conclusion: The review focused on the characterized anticancer natural products and their derivatives with collateral sensitivity, their working mechanisms, and related structure-activity relationships, emphasizing recently identified CS compounds. According to their structural features, these MDR-targeting compounds were mainly classified into the following categories: flavonoids, terpenoids, stilbenes, alkaloids and quinones. The exploration of molecular mechanisms of collateral sensitivity and structural features of anticancer agents with collateral sensitivity provided an effective approach for the clinic treatment of MDR in cancer.

背景：多药耐药（MDR）是癌细胞对多种目前使用的具有不同结构支架和不同抗癌机制的抗肿瘤药物的耐药性。它已被公认为癌症成功治疗的主要障碍之一，导致恶性疾病的转移和复发。

简介：侧枝敏感性 (CS) 是某些化学物质的特征，可以选择性地杀死抗药亚系，而不是产生抗药细胞的亲本细胞系。研究和开发具有旁系敏感性的新候选药物将是克服癌症多药耐药性的有效方法。我们的目标是提供有关发现具有附带敏感性的天然产品的最新信息。

结果和结论：该综述侧重于具有侧枝敏感性的特征性抗癌天然产物及其衍生物、它们的工作机制和相关的构效关系，并强调最近发现的 CS 化合物。根据其结构特征，这些靶向MDR的化合物主要分为以下几类：黄酮类、萜类、芪类、生物碱类和醌类。探索侧支敏感性的分子机制和具有侧支敏感性的抗癌药物的结构特征，为癌症MDR的临床治疗提供了有效途径。