异环磷酰胺氮芥卟啉二聚体的合成及生物活性

高等学校化学学报 ›› 2011, Vol. 32 ›› Issue (8): 1761.

异环磷酰胺氮芥卟啉二聚体的合成及生物活性

王志伟, 郭灿城, 田蜜, 郭琳, 孙腾飞, 郭清虎

湖南大学化学化工学院, 长沙 410082

收稿日期:2010-09-16 修回日期:2010-11-07 出版日期:2011-08-10 发布日期:2011-07-19
通讯作者: 郭灿城 E-mail:ccguo@hnu.edu.cn
基金资助:
国家自然科学基金(批准号: J0830415)资助.

Synthesis and Biological Activities of Ifosfamide Mustards Porphyrin Dimers

WANG Zhi-Wei, GUO Can-Cheng*, TIAN Mi, GUO Lin, SUN Teng-Fei, GUO Qing-Hu

College of Chemistry and Chemical Engineering, Hunan University, Changsha 410082, China

Received:2010-09-16 Revised:2010-11-07 Online:2011-08-10 Published:2011-07-19
Contact: GUO Can-Cheng E-mail:ccguo@hnu.edu.cn
Supported by:
国家自然科学基金(批准号: J0830415)资助.

摘要/Abstract

摘要： 本文以羟基取代卟啉为原料，通过控制反应过程中双卟啉磷酰氯的合成条件，用一锅法合成了5个异环磷酰胺氮芥卟啉二聚体. 所有化合物均经过Ms、1H NMR、31P NMR和元素分析确定结构. 细胞吸附实验和细胞毒性实验表明异环磷酰胺氮芥卟啉二聚体可以选择性富集和杀死肿瘤细胞. 利用荧光光谱考察了异环磷酰胺氮芥卟啉二聚体与牛血清白蛋白（BSA）的相互作用，结果表明卟啉二聚体对BSA的荧光有较强的静态猝灭作用，可以生成稳定的卟啉二聚体-BSA复合物.

关键词: 卟啉二聚体; , 异环磷酰胺氮芥; , 细胞吸附; , 牛血清白蛋白

Abstract: Ifosfamide is one of the most important clinical alkylating agent due to its frequent use in cancer chemotherapy. It does not exhibit any cytotoxic activities in vitro, and requires hepatic oxidative metabolism in vivo to generate an alkylating ifosfamide mustard, which is regarded as the ultimate intracellular alkylating metabolite. However, its clinical uses are restricted due to they can not distinguish tumor cells from normal cells. Porphyrins could selectively accumulate in tumor tissues than in normal tissues. Based on these facts, an efficient one-pot method for the synthesis of ifosfamide mustards porphyrin dimers was achieved by treating hydroxyl substituted porphyrin first with POCl3 then with primary amine. The selective synthesis of ifosfamide mustards porphyrin dimers were achieved simply by controlling the ratio of POCl3 vis hydroxyl porphyrin and the reaction condition during the phosphonation step. Five ifosfamide mustards porphyrin dimers were synthesized accordingly by this one-pot procedure and their structures were affirmed by MS, 1H NMR, 31P NMR and elemental analysis. The MTT tests and the uptake tests showed that ifosfamide mustards porphyrin dimers could selectively accumulate and kill cancer cell. The interaction between ifosfamide mustards porphyrin dimers and bovine serum albumin (BSA) was investigated by fluorescence spectrum. The results showed that the ifosfamide mustards porphyrin dimers own a powerful ability of quenching the fluorescence of BSA via static quenching occurring in the non-covalent porphyrin-BSA complex.

Key words: Porphyrin dimer, Ifosfamide mustard, Cellular uptake, Bovine serum albumin(BSA)

中图分类号:

TrendMD:

王志伟郭灿城田蜜郭琳孙腾飞郭清虎. 异环磷酰胺氮芥卟啉二聚体的合成及生物活性. 高等学校化学学报, 2011, 32(8): 1761.

WANG Zhi-Wei, GUO Can-Cheng*, TIAN Mi, GUO Lin, SUN Teng-Fei, GUO Qing-Hu. Synthesis and Biological Activities of Ifosfamide Mustards Porphyrin Dimers. Chem. J. Chinese Universities, 2011, 32(8): 1761.

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