Optimization of hypocrellin B derivative amphiphilicity and biological activity  

作　　者：LIU Xin XIE Jie ZHANG LuYong CHEN HongXia GUYing ZHAO JingQuan 

机构地区：[1]Beijing National Laboratory for Molecular Sciences (BNLMS), and Key Laboratory of Photochemistry, Institute of Chemistry, Chi- nese Academy of Sciences, Beijing 100080, China [2]Department of Laser Medicine, Chinese People's Libration Army General Hospital, Beijing 100853, China

出　　处：《Chinese Science Bulletin》2009年第12期2045-2050,共6页

基　　金：Supported by the National Natural Science Foundation of China(Grant No.50221201)

摘　　要：To satisfy the dual requirements of the fluent transportation in blood and the affinity to the target tissues of vascular diseases, hypocrellin derivatives with optimized amphiphilicity are expected. In this work, 3-amino-1-propanesulfonic acid and 4-amino-1-butanesulfonic acid substituted hypocrellin B, named compounds 1 and 2, were designed, synthesized in high yields and characterized. Besides greatly strengthened red absorption, the maximum solubility of compound 2 in phosphate buffered saline (PBS) is 4.2 mg/mL which is just enough to prepare an aqueous solution for intravenous injection in clinically acceptable concentration, while the partition coefficient between n-octanol and PBS, 5.6, benefits the cell-uptake and biological activity as well. Furthermore, EPR measurements reveal that the photosensitization activities of the two compounds to generate semiquinone anion radicals, superoxide anion radicals and singlet oxygen are a little bit higher than those of taurine substituted hypocrellin B (THB), but the photodynamic activities to human lung cancer A549 cells are several times that of THB, mainly due to increases in lipophilicity and cell-uptake.To satisfy the dual requirements of the fluent transportation in blood and the affinity to the target tissues of vascular diseases, hypocrellin derivatives with optimized amphiphilicity are expected. In this work, 3-amino-l-propanesulfonic acid and 4-amino-l-butanesulfonic acid substituted hypocrellin B, named compounds 1 and 2, were designed, synthesized in high yields and characterized. Besides greatly strengthened red absorption, the maximum solubility of compound 2 in phosphate buffered saline （PBS） is 4.2 mg/mL which is just enough to prepare an aqueous solution for intravenous injection in clinically acceptable concentration, while the partition coefficient between n-octanol and PBS, 5.6, benefits the cell-uptake and biological activity as well. Furthermore, EPR measurements reveal that the photosensitization activities of the two compounds to generate semiquinone anion radicals, superoxide anion radicals and singlet oxygen are a little bit higher than those of taurine substituted hypocrellin B （THB）, but the photodynamic activities to human lung cancer A549 cells are several times that of THB, mainly due to increases in lipophilicity and cell-uptake.

关 键 词：竹红菌乙素 生物活性 衍生物 优化 超氧阴离子自由基 A549细胞 磷酸盐缓冲液 电子顺磁共振 

分 类 号：O636.1[理学—高分子化学] Q682[理学—化学]