3'-叠氮-3'-脱氧胸苷（AZT）叶酸缀合物的合成、表征及体外测定：靶向基于AZT的抗癌疗法
Synthesis, characterization, and in vitro assay of folic acid conjugates of 3'-azido-3'-deoxythymidine (AZT): toward targeted AZT based anticancer therapeutics.
作者信息
Vortherms Anthony R, Doyle Robert P, Gao Dayuan, Debrah Olivia, Sinko Patrick J
机构信息
Department of Chemistry, Syracuse University, Syracuse, NY 13208-4100, USA.
出版信息
Nucleosides Nucleotides Nucleic Acids. 2008 Feb;27(2):173-85. doi: 10.1080/15257770701795946.
Abstract
Conjugates of three components namely folic acid, poly(ethyleneglycol) and 3 '-azido-3 '-deoxythymidine (AZT) are presented. Folate-PEG units were coupled to AZT to facilitate delivery of the nucleoside into the cell. A convenient separation of the polydisperse PEGylated-folic acid regioisomers produced upon conjugation is described. This is to select for the active gamma-regioisomer over the inactive alpha-regioisomer. In vitro cytotoxicity assays were conducted against an ovarian cell line (A2780/AD) that overexpresses the folate receptor (FR) and compared to a FR free control cell line. Compared to AZT a approximately 20-fold greater potency against the resistant ovarian line was observed for the conjugates.
摘要
本文介绍了由叶酸、聚乙二醇和3'-叠氮基-3'-脱氧胸苷（AZT）三种成分组成的共轭物。叶酸-聚乙二醇单元与AZT偶联，以促进核苷进入细胞。文中描述了一种方便的方法，用于分离共轭反应产生的多分散聚乙二醇化叶酸区域异构体。此方法用于选择活性γ-区域异构体而非无活性的α-区域异构体。针对过表达叶酸受体（FR）的卵巢癌细胞系（A2780/AD）进行了体外细胞毒性试验，并与无FR的对照细胞系进行了比较。与AZT相比，共轭物对耐药卵巢癌细胞系的效力提高了约20倍。
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