七元瓜环对10-羟基喜树碱理化性质及抗癌活性的影响研究

Studies on the Effects of Cucurbit(n=7) uril on the Physicohemical Properties and Anticancer Activity of 10-Hydroxycamptothecin

利用紫外吸收光谱、荧光光谱、相溶解度等方法考察了七元瓜环(Q[7])对10-羟基喜树碱(HCPT)理化性质及抗癌活性的影响。研究结果表明在pH 2.0的盐酸介质中,随着主客体NQ[7]/NHCPT比例的增加,客体HCPT在λ265nm的紫外吸收强度明显下降并且波长发生红移,而在λ425nm的吸收强度却增加并在λ387nm波长处有明显的等吸收点。HCPT的荧光光谱表现出在λ558nm荧光发射峰的荧光强度呈下降趋势并发生波长蓝移现象。摩尔比法和Job法的研究得出主体Q[7]与客体HCPT形成了2∶1的主客体配合物,Reactlab EQULLIBRIA software○R程序计算了紫外吸收法和荧光光谱法的主客体配合物的总稳定常数(β)分别为1.549×1013 L2·mol-2和0.907×1013 L2·mol-2;相溶解度实验的结果表明当Q[7]的浓度为1×10-3mol·L-1时,可使HCPT的溶解度增大约250倍,而利用共蒸发法制备的Q[7]-HCPT固体包合物则可使HCPT在水中的溶解度提高约1170倍;体外人肺癌细胞株A549和人白血病细胞株K562的细胞毒活性测试结果表明,与单纯的HCPT比较,包合物的形成对HCPT的抗癌活性影响不大。

The changes in the physicochemical properties and the anticancer activity of 10-Hydroxycamptothecin（HCPT）in the presence of Cucurbit（n= 7 ）uril（Q[7 ]）were studied by using UV absorption spectroscopy,fluorescence spectroscopy and phase solubility method.The results revealed that in the acid solution （pH 2）,the absorption band of the guest HCPT exhibited a pro-gressively lower absorbance atλ265 nm ,while a progressively higher absorbance atλ425 nm as the ratio of NQ[7]/NHCPT was in-creased.A sharp isosbestic point atλ387 nm was consistent with a simple interaction between Q[7]and HCPT.The emission spec-tra of the guest HCPT also exhibited a progressive decrease in fluorescence intensity atλ558 nm with a violet shift when the ratio of NQ[7]/NHCPT was increased.The measured data from both absorption spectrophotometric and fluorescence spectroscopy analysis fitted to a 2∶1 host：guest complexation,yielded a calculated stable constants （β）of 1.549×10^13 L^2·mol^-2and 0. 907×10^13 L^2 ·mol^-2 respectively through Reactlab EQULLIBRIA software？.The effect of Q[7]on the solubility of HCPT was investigated by using phase solubility method.Upon the addition of Q[7]concentration,the solubility of HCPT was enhanced step by step at the value of pH 2 and an about 250 times advance was attained when the concentration of Q[7]was 1×10^-3 mol·L^-1 ,while the Q[7]-HCPT inclusion complex made by total evaporation method can increase about 1 170 times compared to the pure HCPT.At the end,the mixtures of Q[7 ]and HCPT were tested in terms of cytotoxicity on the human lung cancer cell line A549 and human leukemia cell line K562 to compare their reactivity with the free HCPT and the comparative cytotoxic activity was got for A549 and K562.