腺苷与胞壁酰二肽及去甲胞壁酰二肽衍生物缀合物的合成及其抗增殖活性

Synthesis and antiproliferative activity of conjugates of adenosine with muramyl dipeptide and nor-muramyl dipeptide derivatives.

作者信息

Samsel Monika, Dzierzbicka Krystyna, Trzonkowski Piotr

机构信息

Department of Organic Chemistry, Gdansk University of Technology, ul. Narutowicza 11/12, 80-233 Gdansk, Poland.

出版信息

Bioorg Med Chem Lett. 2014 Aug 1;24(15):3587-91. doi: 10.1016/j.bmcl.2014.05.043. Epub 2014 May 23.

DOI:10.1016/j.bmcl.2014.05.043

PMID:24915876

Abstract

We synthesized a series of MDP(D,D) and nor-MDP(D,D) derivatives conjugated with adenosine through a spacer as potential immunosuppressants. New conjugates 8a-k were evaluated on two leukemia cell lines (Jurkat and L1210) and PBMC from healthy donors. The conjugates 8a-k and MDP(D,D)/nor-MDP(D,D) derivatives 7e, f, i, j were active against L1210 cell line. Unconjugated nor-MDP(D,D) had better antiproliferative properties, but the conjugates 8b, f, g had the highest values of selectivity index. Both cell lines as well as PBMC were resistant to analogs 11a, b with the 6-aminohexanoic linker.

摘要

我们合成了一系列通过间隔基与腺苷共轭的MDP(D,D)和去甲MDP(D,D)衍生物，作为潜在的免疫抑制剂。在两种白血病细胞系（Jurkat和L1210）以及健康供体的外周血单核细胞（PBMC）上对新的共轭物8a - k进行了评估。共轭物8a - k以及MDP(D,D)/去甲MDP(D,D)衍生物7e、f、i、j对L1210细胞系有活性。未共轭的去甲MDP(D,D)具有更好的抗增殖特性，但共轭物8b、f、g的选择性指数值最高。两种细胞系以及PBMC对带有6 - 氨基己酸连接基的类似物11a、b均有抗性。