|本期目录/Table of Contents|

[1]刘文金,曹小冬.HSP90抑制剂前药设计及合成[J].浙江理工大学学报,2023,49-50(自科五):604-611.
 LIU Wenjin,CAO Xiaodong.Design and synthesis of HSP90 inhibitor prodrugs[J].Journal of Zhejiang Sci-Tech University,2023,49-50(自科五):604-611.
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HSP90抑制剂前药设计及合成()
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浙江理工大学学报[ISSN:1673-3851/CN:33-1338/TS]

卷:
第49-50卷
期数:
2023年自科第五期
页码:
604-611
栏目:
出版日期:
2023-09-24

文章信息/Info

Title:
Design and synthesis of HSP90 inhibitor prodrugs
文章编号:
1673-3851 (2023) 09-0604-08
作者:
刘文金曹小冬
浙江理工大学理学院,杭州 310018
Author(s):
LIU Wenjin CAO Xiaodong
School of Science, Zhejiang Sci-Tech University, Hangzhou 310018, China
关键词:
HSP90抑制剂前药缩合酰化多肽前药
分类号:
O622-6
文献标志码:
A
摘要:
为解决热休克蛋白90(Heat shock protein 90,HSP90)抑制剂的周身毒性问题,自主设计并合成了两个HSP90抑制剂的三肽前药P1和P2。以4-(2-羟乙基)哌啶-1-甲酸叔丁酯和1-(溴甲基)-4-硝基苯为起始原料,经羟胺缩合、硝基还原、关环等反应合成HSP90抑制剂HSP90i-1和HSP90i-2;以L-脯氨酸和L-缬氨酸衍生物为原料,经缩合、脱保护、酰化等反应合成多肽连接子M1。将HSP90i-1、HSP90i2分别和M1缩合,得到两个三肽前药P1和P2。1H NMR、LCMS、13-C NMR分析表征结果表明成功合成了两个前药分子两个前药分子被成功合成。该研究具有使用的原料廉价易得、反应都在常温下进行、条件温和可控、总产率较高等特点,为多肽前药的设计及合成提供了新的思路和方法。

参考文献/References:

1 Li Y Y, Zhang T, Schwartz S J, et al. New developments in Hsp90 inhibitors as anti-cancer therapeutics: Mechanisms, clinical perspective and more potentialJ. Drug Resistance Updates, 2009, 12(1/2): 17-27.

2Sidera K, Patsavoudi E. HSP90 inhibitors: Current development and potential in cancer therapyJ. Recent Patents on Anti-Cancer Drug Discovery, 2013, 9(1): 1-20.

3Alarcon S V, Mollapour M, Lee M J, et al. Tumor-intrinsic and tumor-extrinsic factors impacting hsp90- targeted therapyJ. Current Molecular Medicine, 2012, 12(9): 1125-1141.

4]张钟元, 阎爱侠. Hsp90抑制剂的研究进展[J. 中国医药生物技术, 2021, 16(1): 41-50.

5Shrestha L, Bolaender A, Patel H J, et al. Heat shock protein (HSP) drug discovery and development: Targeting heat shock proteins in diseaseJ. Current Topics in Medicinal Chemistry, 2016, 16(25): 2753-2764.

6Liu N X, Chen Q H, Zhang Q Q, et al. The application of prodrug-based drug delivery strategy in anticancer drugsJ. Current Topics in Medicinal Chemistry, 2021, 21(24): 2184-2204.

7Zawilska J B, Wojcieszak J, Olejniczak A B. Prodrugs: A challenge for the drug developmentJ. Pharmacological Reports, 2013, 65(1): 1-14.

8Zhang T, Yang X R, Xu W P, et al. Heat shock protein 90 promotes RNA helicase DDX5 accumulation and exacerbates hepatocellular carcinoma by inhibiting autophagyJ. Cancer Biology & Medicine, 2021, 18(3): 693-704.

9Daneri-Becerra C, Galigniana M D. The Hsp90-binding immunophilin FKBP52 enhances neurodifferentiation and neuroregeneration in murine modelsJ. Neural Regeneration Research, 2022, 17(3): 555-556.

10]林智才, 陈燕丽, 苏小清, . Hsp90抑制剂减弱肝癌耐药细胞株对索拉非尼诱导铁死亡的耐受性[J. 现代肿瘤医学, 2022, 30(21): 3862-3868.

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备注/Memo

备注/Memo:
收稿日期: 2023-01-18
网络出版日期:2023-06-07

作者简介: 刘文金(1995-),男,甘肃天水人,硕士研究生,主要从事有机物合成方面的研究
通信作者: 曹小冬,E-mail: sheldon.cao@eubulusbio.com

更新日期/Last Update: 2023-09-19