基于紫杉醇和氮芥协同前药的设计、合成与活性评价

doi:10.5246/jcps.2013.02.018

基于紫杉醇和氮芥协同前药的设计、合成与活性评价

邵军超, 林海霞^*, 崔永梅, Shaoman Yin, Erwin G Van Meir, 黄嘉辰

1. 上海大学理学院化学系, 上海 200444
2. 艾默利大学医学院, 美国亚特兰大 30322

收稿日期:2012-10-24 修回日期:2012-12-20 出版日期:2013-03-18 发布日期:2013-03-18
通讯作者: 林海霞*

Design, synthesis and evaluation of the cytotoxicity of a N-mustard and paclitaxel conjugate prodrug

Junchao Shao, Haixia Lin^*, Yongmei Cui, Shaoman Yin, Erwin G Van Meir, Jiachen Huang

1. Department of Chemistry, School of Science, Shanghai University, Shanghai 200444, China
2. Laboratory of Molecular Neuro-Oncology, Departments of Neurosurgery, Hematology and Medical Oncology, and Emory Winship Cancer Institute, Emory University School of Medicine, Atlanta, Georgia 30322, USA

Received:2012-10-24 Revised:2012-12-20 Online:2013-03-18 Published:2013-03-18
Contact: Haixia Lin*

摘要/Abstract

摘要：

本文完成了一种新型紫杉醇-氮芥前药分子的合成及初步活性评价。化学模拟还原活化表明硝基还原后此前药可释放紫杉醇, 并利用人胶质细胞瘤LN229、D54MG、U251MG三个细胞株在正常及厌氧条件下对此前药的细胞毒性进行了初步评价。

关键词: 紫杉醇, 氮芥, 前药, 厌氧

Abstract:

The syntheses and preliminary biological evaluation of a potentially bioreductive N-mustard and paclitaxel conjugate prodrug 3 targeting hypoxic tumor tissue are described. Aromatic nitro group was used as the bio-reductive trigger. Generation of paclitaxel occurred after reduction via a subsequent mechanism of “cyclization-cyclization-extrusion”. The prodrug was stable in PBS (pH = 7.4) and released paclitaxel after chemical reduction of the nitro functionality. In aerobic cytotoxicity assays, it exhibited diminished cytotoxicity and is a candidate for further biological evaluation.

Key words: Paclitaxel, N-mustard, Prodrug, Hypoxia

中图分类号:

R916

Supporting: Foundation items: National Natural Science Foundation of China (Grant No. 21272154 and 30672506). Leading Academic Discipline Project of Shanghai Municipal Education Commission (Project No. J50102).
^*Corresponding author. Tel.: 86-21-66136050; Fax: 86-21-66133039

邵军超, 林海霞^*, 崔永梅, Shaoman Yin, Erwin G Van Meir, 黄嘉辰. 基于紫杉醇和氮芥协同前药的设计、合成与活性评价[J]. , DOI: 10.5246/jcps.2013.02.018.

Junchao Shao, Haixia Lin^*, Yongmei Cui, Shaoman Yin, Erwin G Van Meir, Jiachen Huang. Design, synthesis and evaluation of the cytotoxicity of a N-mustard and paclitaxel conjugate prodrug [J]. , DOI: 10.5246/jcps.2013.02.018.

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