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Progress Toward the Development of Noscapine and Derivatives as Anticancer Agents

机译:Noscapine及其衍生物作为抗癌药物的开发进展

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摘要

Many nitrogen-moiety containing alkaloids derived from plant origins are bioactive and play a significant role in human health and emerging medicine. Noscapine, a phthalideisoquinoline alkaloid derived from Papaver somniferum, has been used as a cough suppressant since the mid 1950s, illustrating a good safety profile. Noscapine has since been discovered to arrest cells at mitosis, albeit with moderately weak activity. Immunofluorescence staining of microtubules after 24 h of noscapine exposure at 20 mu M elucidated chromosomal abnormalities and the inability of chromosomes to complete congression to the equatorial plane for proper mitotic separation (Proc. Natl. Acad. Sci. U. S. A. 1998, 95, 1601-1606). A number of noscapine analogues possessing various modifications have been described within the literature and have shown significantly improved antiprolific profiles for a large variety of cancer cell lines. Several semisynthetic antimitotic alkaloids are emerging as possible candidates as novel anticancer therapies. This perspective discusses the advancing understanding of noscapine and related analogues in the fight against malignant disease.
机译:许多源自植物的含氮生物碱具有生物活性,并在人类健康和新兴医学中发挥重要作用。自1950年代中期以来,Noscapine(一种衍生自罂粟的邻苯二甲酰异喹啉生物碱)已被用作止咳药,显示出良好的安全性。此后,尽管活性适度弱,但已发现Noscapine可将细胞停在有丝分裂状态。在20μM的Noscapine暴露24 h后对微管进行免疫荧光染色,阐明了染色体异常和染色体无法完全向赤道平面汇合以进行适当的有丝分裂分离(Proc。Natl。Acad。Sci。USA 1998,95,1601-1606 )。在文献中已经描述了许多具有各种修饰的诺丝卡因类似物,并且它们已经显示出针对多种癌细胞系的显着改善的抗多态性谱。几种半合成抗有丝分裂生物碱正在作为新型抗癌疗法出现。该观点讨论了在抗击恶性疾病中对诺斯卡定及其相关类似物的先进理解。

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