大黄酸氨基酸衍生物合成及放射增敏作用的初步研究  

Synthesis and Radiosensitizing Effects of Rhein-Amino Acid Derivatives

作　　者：李济洋[1] 朱泽红 郝建秀[1] 周则卫[1] 李瑞峰[1] 李光强[1] 徐文清[1] 

机构地区：[1]中国医学科学院北京协和医学院放射医学研究所药物室,天津300192

出　　处：《天然产物研究与开发》2013年第6期752-758,共7页Natural Product Research and Development

基　　金：中国医学科学院放射医学研究所基金(ST1221);天津市应用基础及前沿技术研究计划(10JCYBJCI14500)

摘　　要：本文以大黄酸为先导化合物,将其3位羧基分别与亮氨酸、异亮氨酸、天冬氨酸、谷氨酸、色氨酸、蛋氨酸、脯氨酸和2-氨基丁酸的氨基形成酰胺键,合成8个衍生物,再碱化得钠盐。采用MTT法测定这些化合物对H460肺癌细胞的体外生长抑制活性。选取活性较好的化合物,在相应的IC15和IC20浓度下,初步测定放射增敏活性。结果显示除大黄酰色氨酸钠在24 h和48 h和大黄酰脯氨酸钠在48 h有促进增殖作用,其余大黄酸氨基酸钠盐衍生物对肺癌H460细胞具有显著的浓度和时间依赖型生长抑制活性。其中大黄酰亮氨酸钠作用24、48、72 h的IC50值分别为279.863、92.735、65.567μM,大黄酰异亮氨酸钠作用24、48、72 h的IC50值分别为205.251、164.222、77.442μM,抑制作用较大黄酸钠有明显提高(P<0.05)。初步放射增敏活性测定表明,大黄酰异亮氨酸钠在相应的IC15和IC20浓度下与照射联用,测得的OD值均小于单纯照射组,说明它有放射增敏作用。此结果可为后续寻找高效低毒的肿瘤放射治疗增敏药物提供研究基础。In this paper, rhein was used as the lead compound, and its carboxyl group was condensed with amino group of leucine （Leu）, isoleucine （Ile）, aspartic acid （ Asp ） , glutamic acid （Glu）, tryptophan （Trp）, methionine （Met）, proline （Pro）, 2-amino butyric acid, resulting in 8 amlde derivatives. MTT assay was used to measure the inhibition activities of the 8 amide derivatives on proliferation of pulmonary carcinoma Hd-60 cells. Compounds with better activity were selected to investigate their radiosensitizing activities in corresponding IC15and IC20concentration. The inhibitory effects of these compounds on proliferation of H460 ceils manifested in a dose and time-dependent manner, except that sodium rhein-Trp induced proliferation in 24 h and 48 h and sodium rbein-Pro induced proliferation in 48h. The half inhibitory concentrations （ IC50 ） of the sodium rhein-Leu were 279. 863 μM （24 h）, 92. 735 μM （48 h）, 65. 567 μM （72 h）, while the IC50of rhein-Ile were 205. 251 μM （24 h）, 164. 222 μM （48 h）, 77. 442 μM （72 h）, both better than sodium rheim Preliminary radiosensifizing test demonstrated that OD values were lower after treatment by combining sodium rhein-Ile with radiation than by radiation alone. That indicated that sodium rhein-ne was shown with preliminary radiosensifizing effect on H460 cells in vitro. This result may be helpful for finding radiosensitizer with higher efficiency and less toxicity.

关 键 词：大黄酸 羟基蒽醌 H460 细胞 放射增敏 

分 类 号：Q946[生物学—植物学] R285[医药卫生—中药学]