Synthesis and biological activity of mycophenolic acid-amino acid derivatives

被引：34
|
作者：
Iwaszkiewicz-Grzes, Dorota [1 ]
Cholewinski, Grzegorz [1 ]
Kot-Wasik, Agata [2 ]
Trzonkowski, Piotr [3 ]
Dzierzbicka, Krystyna [1 ]
机构：
[1] Gdansk Univ Technol, Dept Organ Chem, PL-80233 Gdansk, Poland
[2] Gdansk Univ Technol, Dept Analyt Chem, PL-80233 Gdansk, Poland
[3] Med Univ Gdansk, Dept Clin Immunol & Transplantol, PL-80211 Gdansk, Poland
来源：
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY | 2013年 / 69卷
关键词：
Mycophenolic acid derivatives; Amino acid derivatives; IMPDH inhibitors; Cytotoxic activity; INOSINE MONOPHOSPHATE DEHYDROGENASE; 5'-MONOPHOSPHATE DEHYDROGENASE; TRANSPLANT RECIPIENTS; ANALOGS; INHIBITION; ALKALOIDS; MOFETIL; SODIUM;
D O I：
10.1016/j.ejmech.2013.09.026
中图分类号：
R914 [药物化学];
学科分类号：
100701 ;
摘要：
In search of new immunosuppressants we synthesized 11 amino acids derivatives of MPA as methyl esters 10a-k using EDCl/DMAP and their corresponding amino acid derivatives in free acid form ha k by hydrolysis of ester group with LiOH/MeOH. New analogs were evaluated as growth inhibitors of lymphoid cell line (Jurkat) and human peripheral blood mononuclear cells (PBMC) from healthy donors. According to obtained results recovering of free carboxylic group increased their activity. Additionally, the cytotoxic properties depends on the substituent and configuration at chiral center in amino acid unit. The compounds 10j, lie and 11h exhibited higher potency than MPA 1 in vitro. (C) 2013 Elsevier Masson SAS. All rights reserved.
引用
收藏
页码：863 / 871
页数：9
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