摘要
严重的抗癌形势以及多药耐药(MDR)癌细胞的出现,迫切需要开发具有不同作用机制的新型抗癌药物。大量的天然生物碱,如紫杉醇、长春碱、喜树碱等已被成功开发成为化疗药物。在这些天然产物的成功应用之后,本文综述了26种异喹啉类生物碱(共379种生物碱),包括苄基四氢异喹啉、阿扑啡、氧代阿扑啡、异氧代阿扑啡、二甲基阿扑啡、双苄基异喹啉、四氢前驱黄连素、原小檗碱、原松、二氢苯并菲、苯并菲。根据其对各种癌细胞的细胞毒性和MDR逆转活性,总结了南特瑞丁、二苯并菲定二聚体、吐根、简单异喹啉、帕夫碱、蒙大丁、赤藓红、白屈菜碱、对苯二甲酸异喹啉、氮杂荧蒽、邻苯二异喹啉、萘基异喹啉、石蒜素、海百合、麻醉剂和菲蒽酮。此外,还讨论了不同类型异喹啉生物碱的构效关系。有趣的是,一些阿扑啡、氧磷卟啉、异氧磷卟啉、双苄基异喹啉和原小檗碱生物碱的抗癌活性或抗MDR作用比阳性对照组更强,被认为是发现新的抗癌药物或铅化合物的有吸引力的靶点
关键词: 异喹啉生物碱,抗癌,MDR,结构-活性关系,天然产物,阿朴啡,奥沙普啡,双苯异喹啉。
Current Medicinal Chemistry
Title:Anticancer and Reversing Multidrug Resistance Activities of Natural Isoquinoline Alkaloids and their Structure-activity Relationship
Volume: 25 Issue: 38
关键词: 异喹啉生物碱,抗癌,MDR,结构-活性关系,天然产物,阿朴啡,奥沙普啡,双苯异喹啉。
摘要: 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.
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Cite this article as:
Anticancer and Reversing Multidrug Resistance Activities of Natural Isoquinoline Alkaloids and their Structure-activity Relationship, Current Medicinal Chemistry 2018; 25 (38) . https://dx.doi.org/10.2174/0929867324666170920125135
DOI https://dx.doi.org/10.2174/0929867324666170920125135 |
Print ISSN 0929-8673 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-533X |
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