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

基于紫杉醇和氮芥协同前药的设计、合成与活性评价(英文)

作　　者：邵军超 林海霞[1] 崔永梅[1] Shaoman Yin Erwin G Van Meir 黄嘉辰 

机构地区：[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

出　　处：《Journal of Chinese Pharmaceutical Sciences》2013年第2期137-143,共7页中国药学（英文版）

基　　金：support from the National Natural Science Foundation of China(Grant No.21272154and30672506);Leading Academic Discipline Project of Shanghai Municipal Education Commission(Project No.J50102);EGVM acknowledges the US National Institutes of Health(NCI grant R01CA116804)

摘　　要：The syntheses and preliminary biological evaluation of a potentially bioreductive A-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 fimctionality. In aerobic cytotoxicity assays, it exhibited diminished cytotoxicity and is a candidate for further biological evaluation.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：PACLITAXEL N-mustard PRODRUG Hypoxia 

分 类 号：R914[医药卫生—药物化学]