吲哚美辛-PEG-1500酯的合成及体外抗肿瘤活性

Synthesis of indomethacin-PEG-1500 ester and its anti-tumor activity in vitro

目的合成吲哚美辛-聚乙二醇-1500(polyethylene glycol,PEG-1500)酯并考察其在水中的溶解度和体外抗肿瘤活性。方法通过吲哚美辛的羰基与PEG的羟基反应合成目标化合物羧酸酯;测定吲哚美辛-PEG-1500酯和吲哚美辛在水中的溶解度和熔点;以吲哚美辛原料药作为阳性对照药,采用MTT法测试目标化合物对HCT116人结肠癌细胞的生长抑制活性。结果合成的目标化合物的结构经IR、1H-NM R得到确证;吲哚美辛-PEG-1500酯比吲哚美辛有更好的水溶性;吲哚美辛和吲哚美辛-PEG-1500酯对HCT116人结肠癌细胞有相近的抑制作用。结论吲哚美辛-PEG-1500酯的合成不仅解决了IM C水溶性差的问题,而且也为其他同属于有机弱酸类且水溶性较差的药物解决相同或相似的问题提供了一个新的思路,具有较好的发展前景。

Objective To synthesize indomethacin-polyethylene glycol（ PEG）-1500 ester,and evaluate the solubility and its anti-tumor activity in vitro. Methods The carboxyl in indomethacin is reacted with hydroxyl group of PEG to form the carboxyester of the target compound. The melting point and solubility of indomethacin-PEG-1500 ester and indomethacin were measured. The growth inhibitory activity of the indomethacin-PEG-1500 ester on human colon cancer cell line HCT116 was determined by MTT method.The inhibitory ratio of indomethacin-PEG-1500 ester is comparative to that of free indomethacin as control.Results The structure of indomethacin-PEG-1500 ester was confirmed by means of IR and ^1H-NMR. The indomethacin-PEG-1500 ester had better solubility than indomethacin. Indomethacin had the same inhibitory activity as indomethacin-PEG-1500 esteron human colon cancer cell line HCT116. Conclusions Synthesis of indomethacin-PEG-1500 not only solves the problem of IMC poor solubility in water,but also provides a newway for the medicines which belong to organic weak acids and have poor water solubilities. Our method has good development prospects.