Medicinal Chemistry, Monash Institute of Pharmaceutical Sciences, Monash University (Parkville Campus), 381 Royal Parade, Parkville, Victoria 3052 Australia.
J Med Chem. 2015 Aug 13;58(15):5699-727. doi: 10.1021/jm501180v. Epub 2015 Apr 16.
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 μM 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.
许多来源于植物的含氮部分的生物碱具有生物活性,在人类健康和新兴医学中发挥着重要作用。那可丁是一种来源于罂粟的苯酞异喹啉生物碱,自 20 世纪 50 年代中期以来一直被用作镇咳药,展示了良好的安全性。此后,人们发现那可丁可以使细胞在有丝分裂时停滞,尽管活性适中较弱。在 20 μM 的那可丁暴露 24 小时后,通过免疫荧光染色微管,阐明了染色体异常以及染色体无法完成向赤道面的 congression 以进行适当的有丝分裂分离(Proc. Natl. Acad. Sci. U. S. A. 1998, 95, 1601-1606)。文献中已经描述了许多具有各种修饰的那可丁类似物,并显示出对多种癌细胞系有显著改善的抗增殖作用。几种半合成抗有丝分裂生物碱正在成为新型抗癌疗法的候选药物。本文讨论了在对抗恶性疾病方面,那可丁和相关类似物的研究进展。