Optimization of hypocrellin B derivative amphiphilicity and biological activity |
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Authors: | Xin Liu Jie Xie LuYong Zhang HongXia Chen Ying Gu JingQuan Zhao |
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Institution: | (1) Beijing National Laboratory for Molecular Sciences (BNLMS), and Key Laboratory of Photochemistry, Institute of Chemistry, Chinese Academy of Sciences, Beijing, 100080, China;(2) Department of Laser Medicine, Chinese People’s Libration Army General Hospital, Beijing, 100853, China |
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Abstract: | 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.
Supported by the National Natural Science Foundation of China (Grant No. 50221201) |
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Keywords: | hypocrellin derivatives photodynamic therapy to vas capillary diseases drug delivery target affinity EPR spectra phtotoxicity |
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