PEG-Epothilone B的合成及其初步抗肿瘤活性研究.pdfVIP

中国医药工业杂志 Chinese Journal of Pharmaceuticals 2016, 47 (1 2) • 1507 • PEG-Epothilone B 的合成及其初步抗肿瘤活性研究 汪海波，张伟，陈通通，蔡正江，朱天民 (浙江海正药业股份有限公司，浙江台州 318000) 摘要:以埃博霉素B 为先导化合物，用不同分子量的聚乙二醇衍生物 (PEG-NH 或PEG-SH) 对其进行修饰，合成了 11 2 个水溶性埃博霉素B 衍生物，并通过NMR和 MS 确证了其结构。采用 MTT 法考察了目标化合物对人体肝癌细胞HepG2 的抑制作用，并通过考察其对人体原代肝细胞的半数致死率评价了目标化合物的毒性。结果表明，目标化合物对HepG2 均表现出较好的抑制作用，对人体原代肝细胞毒性明显下降，水溶性也得到明显改善。 关键词:埃博霉素B; 聚乙二醇:抗肿瘤活性:水溶性:低毒性 中图分类号: R979 .1 文献标志码:A 文章编号: 1001-8255 (2016) 12-1507-06 DOI: 10.1 6522/j.c出i功ph.20 16.1 2.005 Synthesis and Anti-tumor Effect ofPEG-Epothilone B WANG Haibo , ZHANG Wei , CHEN Tongtong, CAI Zhengjia吨， ZHU Tianmin (Zhejiang Hisun Pharmaceutical Co., Ltd. , Taizhou 318000) ABSTRACT: Epothilone B was modified by the polyethylene glycol derivatives with different molecular weights (PEG-NH2 or PEG-SH) to give eleven novel Epothilone B derivatives. The structures were confirmed by NMR and MS. The inhibitory effectes of the target compounds on the human hepatoma cells HepG2 and human primary hepatocytes were detected by MTT assay. The results suggested that, the target compounds exhibited good inhibition on HepG2 cell- lines , lower toxicity on human primary hepatocytes , and better solubility in water. Key words: Epothilone B; polyethylene glycol (PEG) ; anti-tumor effect; water-solubility; low toxicity Epothilones 是一类大环内醋类化合物，具有广 肠癌等肿瘤显示出强效的治疗作用，对于对紫杉醇 耐药的肿瘤仍表现出有效的抑制作用 [1-3J 。其抗肿 谱抗肿瘤活性，它对乳腺癌、前列腺癌、肺癌和结