Hunan Co-Innovation Center for Utilization of Botanical Functional Ingredients & College of Veterinary Medicine, Hunan Agricultural University, Changsha, China.
College of Pharmacy, Hunan University of Chinese Medicine, Changsha, China.
Curr Med Chem. 2018;25(38):5088-5114. doi: 10.2174/0929867324666170920125135.
The severe anticancer situation as well as the emergence of multidrug-resistant (MDR) cancer cells has created an urgent need for the development of novel anticancer drugs with different mechanisms of action. A large number of natural alkaloids, such as paclitaxel, vinblastine and camptothecin have already been successfully developed into chemotherapy agents. Following the success of these natural products, in this review, twenty-six types of isoquinoline alkaloids (a total of 379 alkaloids), including benzyltetrahydroisoquinoline, aporphine, oxoaporphine, isooxoaporphine, dimeric aporphine, bisbenzylisoquinoline, tetrahydroprotoberberine, protoberberine, protopine, dihydrobenzophenanthridine, benzophenanthridine, benzophenanthridine dimer, ipecac, simple isoquinoline, pavine, montanine, erythrina, chelidonine, tropoloisoquinoline, azafluoranthene, phthalideisoquinoline, naphthylisoquinoline, lycorine, crinane, narciclasine, and phenanthridone, were summarized based on their cytotoxic and MDR reversing activities against various cancer cells. Additionally, the structure-activity relationships of different types of isoquinoline alkaloid were also discussed. Interestingly, some aporphine, oxoaporphine, isooxoaporphine, bisbenzylisoquinoline, and protoberberine alkaloids display more potent anticancer activities or anti-MDR effects than positive control against the tested cancer cells and are regarded as attractive targets for discovery new anticancer drugs or lead compounds.
严峻的抗癌形势以及多药耐药（MDR）癌细胞的出现，促使人们迫切需要开发具有不同作用机制的新型抗癌药物。大量天然生物碱，如紫杉醇、长春碱和喜树碱，已成功开发为化疗药物。在这些天然产物取得成功的基础上，本综述总结了 26 种异喹啉生物碱（共 379 种生物碱），包括苯甲基四氢异喹啉、阿朴啡、氧化阿朴啡、异氧化阿朴啡、二聚阿朴啡、双苄基异喹啉、四氢原小檗碱、原小檗碱、普罗托品、二氢苯并菲啶、苯并菲啶、苯并菲啶二聚体、吐根碱、简单异喹啉、帕凡碱、蒙那宁、石蒜碱、 Chelidonium、刺桐异喹啉、吖啶酮、苯酞异喹啉、萘基异喹啉、石蒜碱、藜芦烷、Narciclasine 和菲啶酮，根据它们对各种癌细胞的细胞毒性和 MDR 逆转活性进行了总结。此外，还讨论了不同类型异喹啉生物碱的结构-活性关系。有趣的是，一些阿朴啡、氧化阿朴啡、异氧化阿朴啡、双苄基异喹啉和原小檗碱生物碱对测试的癌细胞显示出比阳性对照更强的抗癌活性或抗 MDR 作用，被认为是发现新抗癌药物或先导化合物的有吸引力的靶标。
