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目的为了解决抗肿瘤天然产物紫草素非选择性的细胞毒性,制备紫草素磺酸钠衍生物并测定其抗肿瘤活性及选择性,以寻找活性更好、毒性更低的先导化合物。方法以2-(1-羟基-4-甲基-3-戊烯基)-1,4,5,8-四甲氧基萘为原料,经侧链羟基酯化、硝酸铈铵(CAN)氧化及共轭加成等4步反应,合成了水溶性的5,8-二甲基紫草素亚硫酸氢钠加成产物(目标物)。采用噻唑蓝(MTT)法测定目标化合物对人前列腺癌细胞DU145、人乳腺癌细胞M CF-7及人白血病细胞K562的生长抑制作用及选择性。结果与结论合成了8个未见文献报道的紫草素磺酸钠衍生物,其结构经1H-NM R、13C-NM R、HSQC及HM BC谱确证。M TT法测试结果表明,目标化合物对人白血病K562细胞具有一定的选择性,与先导物相比较,其水溶性得到明显改善。合成了新型紫草素磺酸钠衍生物,并初步分析了其构效关系,为紫草素类抗肿瘤新药的研究提供了理论依据。
ObjectiveTo resolve the non-selective cytotoxicity of shikonin, a natural product of tumor, a sodium shikonin sulfonate derivative was prepared and its anti-tumor activity and selectivity were determined in order to find a more active and less toxic lead compound. Methods The product of 2 - (1-hydroxy-4-methyl-3-pentenyl) -1,4,5,8-tetramethoxynaphthalene was prepared by side chain hydroxy esterification, ceric ammonium nitrate (CAN) Oxidation and conjugate addition 4-step reaction, the synthesis of water-soluble 5,8-dimethyl shikonin sodium bisulfite addition product (target). The inhibitory effect and selectivity of the target compound on the growth of human prostate cancer cell line DU145, human breast cancer cell line M CF-7 and human leukemia cell line K562 were determined by MTT assay. RESULTS AND CONCLUSIONS Eight novel sodium shikonin sulfonate derivatives were synthesized and their structures were confirmed by 1H-NM R, 13C-NM R, HSQC and HM BC spectra. M TT method test results show that the target compound on human leukemia K562 cells have a certain selectivity, compared with the lead, the water solubility was significantly improved. A novel sodium shikonin sulfonate derivative was synthesized and its structure-activity relationship was analyzed preliminarily, which provided a theoretical basis for the study of shikonin anti-tumor new drug.