泽布勒林：一种用于基于表观遗传学的癌症化疗策略的独特分子。其化学与生物学的神奇之处。

Zebularine: a unique molecule for an epigenetically based strategy in cancer chemotherapy. The magic of its chemistry and biology.

作者信息

Marquez Victor E, Barchi Joseph J, Kelley James A, Rao Kambhampati V R, Agbaria Riad, Ben-Kasus Tsipi, Cheng Jonathan C, Yoo Christine B, Jones Peter A

机构信息

Laboratory of Medicinal Chemistry, Center for Cancer Research, NCI at Frederick, NIH, Frederick, MD 21702, USA.

出版信息

Nucleosides Nucleotides Nucleic Acids. 2005;24(5-7):305-18. doi: 10.1081/ncn-200059765.

DOI:10.1081/ncn-200059765

PMID:16247946

Abstract

1-(beta-D-ribofuranosyl)-1,2-dihydropyrimidin-2-one (zebularine) is structurally 4-deamino cytidine. The increased electrophilic character of this simple aglycon endows the molecule with unique chemical and biological properties, making zebularine a versatile starting material for the synthesis of complex nucleosides and an effective inhibitor of cytidine deaminase and DNA cytosine methyltransferase. Zebularine is a stable, antitumor agent that preferentially targets cancer cells and shows activity both in vitro and in experimental animals, even after oral administration.

摘要

1-（β-D-呋喃核糖基）-1,2-二氢嘧啶-2-酮（泽布勒林）在结构上是4-脱氨基胞苷。这种简单苷元亲电特性的增强赋予了该分子独特的化学和生物学性质，使泽布勒林成为合成复杂核苷的通用起始原料以及胞苷脱氨酶和DNA胞嘧啶甲基转移酶的有效抑制剂。泽布勒林是一种稳定的抗肿瘤药物，优先靶向癌细胞，并且即使在口服给药后，在体外和实验动物中均显示出活性。