药学学报, 2021, 56(10): 2742-2760
引用本文:
杨悦, 李得峰*, 罗婷, 史浩良, 张永强*. 那可丁结构改造与抗肿瘤活性研究进展[J]. 药学学报, 2021, 56(10): 2742-2760.
YANG Yue, LI De-feng*, LUO Ting, SHI Hao-liang, ZHANG Yong-qiang*. Structural modification and anti-cancer activity of noscapine[J]. Acta Pharmaceutica Sinica, 2021, 56(10): 2742-2760.

那可丁结构改造与抗肿瘤活性研究进展
杨悦, 李得峰*, 罗婷, 史浩良, 张永强*
华东理工大学药学院, 上海 200237
摘要:
天然产物结构改造,是抗肿瘤新药开发的有效途径。那可丁是一个来源于阿片的苯酞四氢异喹啉类生物碱,最早作为非处方止咳药在临床上使用,口服有效,对人体没有明显的毒副作用。近年来,该化合物被发现可通过干扰微管聚合等多种作用机制,有效抑制肿瘤细胞的恶性增殖,表现出较好的新药开发前景。有鉴于此,以那可丁为先导化合物,通过结构改造,研究构效关系,提高抗肿瘤活性,优化药代动力学性质,阐明作用机制,开展新药创制,引起了广泛关注。然而由于全合成发展相对滞后,目前结构改造主要是基于半合成路线。本综述主要聚焦近年来基于半合成的那可丁结构改造和抗肿瘤活性研究,并对未来的发展方向和开发前景进行了初步的展望。
关键词:    那可丁      结构改造      抗肿瘤      研究进展     
Structural modification and anti-cancer activity of noscapine
YANG Yue, LI De-feng*, LUO Ting, SHI Hao-liang, ZHANG Yong-qiang*
School of Pharmacy, East China University of Science and Technology, Shanghai 200237, China
Abstract:
The structural modification of natural product represents a powerful tool for anti-cancer drug discovery. Noscapine, as a phthalideisoquinoline alkaloid from opium, has been used as an over-the-counter antitussive drug with excellent oral bioavailability and low toxicity. Recently, the potential of this compound as a particularly attractive lead for anti-cancer drug discovery has been demonstrated. Multiple mechanisms, especially the interference of tubulin polymerization, might be involved. Thereafter, various structural modifications based on semisynthetic routes, which aims to improve the anti-cancer activity and pharmacokinetic properties, as well as to probe the mechanism, has been performed. Several analogues are emerging as possible candidates as novel anticancer therapies. This perspective mainly discusses the advancing noscapine and related analogues in the fight against malignant disease in recent years. Furthermore, the future directions of this evolving field were also preliminary prospected.
Key words:    noscapine    structural modification    anticancer    research progress   
收稿日期: 2021-03-04
DOI: 10.16438/j.0513-4870.2021-0303
基金项目: 国家自然科学基金面上项目(21871086).
通讯作者: 李得峰,Tel:15216732283,E-mail:intelligentbee@sina.com;张永强,Tel:15900685803,E-mail:yongqiangzhang@ecust.edu.cn
Email: intelligentbee@sina.com;yongqiangzhang@ecust.edu.cn
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