文献类型：期刊文献

中文题名：邻硝基苯乙酸作为载体的异羟肟酸类化合物的设计、合成及活性评价

英文题名：Design,synthesis and biological evaluation of hydroxamic acid compounds with 2-nitrophenylacetic acid as carrier

作者：邵长江[1];李靖[2];赵静思[2];张阳[2];贺殿[1,2]

第一作者：邵长江

机构：[1]甘肃中医药大学附属医院,兰州730000;[2]兰州大学药物化学研究所,兰州730000

第一机构：甘肃中医药大学第二附属医院

年份：2016

卷号：14

期号：4

起止页码：385

中文期刊名：中南药学

外文期刊名：Central South Pharmacy

收录：CSTPCD

语种：中文

中文关键词：邻硝基苯乙酸;组蛋白去乙酰化酶;合成;抗肿瘤活性

外文关键词：2-nitrophenylacetic acid; histone deacetylases; synthesis; antitumor activity

摘要：目的为了提高苯基取代的异羟肟酸类化合物对肿瘤细胞的选择性,并降低对正常细胞的毒副作用,本课题组设计并合成以邻硝基苯乙酸作为载体的新型异羟肟酸类化合物。方法以硝基苯衍生物,邻硝基苯乙酸等为原料合成目标化合物。MTT法检测化合物对A549、BEL-7402、HepG2和MGC-803的抑制作用,通过组蛋白去乙酰化酶抑制实验进一步验证化合物活性,并通过急性毒性实验测定化合物的毒性。结果化合物6e、6f对A549细胞的抑制作用优于阳性对照药伏立诺他。通过组蛋白去乙酰化酶抑制实验发现,化合物6e、6f均具有较好的酶抑制作用,与MTT实验结果基本一致,并从急性毒性实验结果得出此类化合物的毒性较阳性对照药伏立诺他小。结论以邻硝基苯乙酸作为载体的此类化合物,可降低对正常细胞的毒副性,并且能增加该类化合物在体内抗肿瘤活性,有进一步研究的价值。
Objective A series of phenyl-substituted hydroxamic acid compounds with 2-nitrophenylacetic acid as carrier were designed and synthesized to improve the selectivity and reduce the toxicity to normal cells. Methods The nitrobenzene derivatives and 2-nitrophenylacetic acid were chosen to synthesize the target compounds. The A549, BEL-7402, HepG2 and MGC-803 were chosen to investigate the inhibitory effect on cell proliferation of target compounds by MTT assay. The compounds activities were verified through enzyme inhibitor test and the toxicity was evaluated through acute toxicity test. Results The compounds 6e and 6f showed better antitumor activity on A549 than the positive control SAHA（vorinostat） and had better enzyme inhibition. The compounds we have synthesized had lower cytotoxicity to normal cells compared to the positive control SAHA. Conclusion The target compounds with 2-nitrophenylacetic acid as carrier can reduce the cytotoxicity to normal cells and improve the selectivity to cancer cells, which merit further study.