Samsel Monika, Dzierzbicka Krystyna, Trzonkowski Piotr
Department of Organic Chemistry, Gdansk University of Technology, ul. Narutowicza 11/12, 80-233 Gdansk, Poland.
Department of Organic Chemistry, Gdansk University of Technology, ul. Narutowicza 11/12, 80-233 Gdansk, Poland.
Bioorg Med Chem Lett. 2014 Aug 1;24(15):3587-91. doi: 10.1016/j.bmcl.2014.05.043. Epub 2014 May 23.
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.
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。
