PEG-Epothilone B的合成及其初步抗肿瘤活性研究

Synthesis and Anti-tumor Effect of PEG-Epothilone B

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_2或PEG-SH)对其进行修饰,合成了11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。

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.