Synthesis and antitumor activity of conjugates of muramyldipeptide or normuramyldipeptide with hydroxyacridine/acridone derivatives

被引:58
作者
Dzierzbicka, K [1 ]
Kolodziejczyk, AM [1 ]
机构
[1] Gdansk Tech Univ, Dept Organ Chem, PL-80952 Gdansk, Poland
关键词
D O I
10.1021/jm020991m
中图分类号
R914 [药物化学];
学科分类号
100701 ;
摘要
A series of MDP (muramyldipeptide) or nor-MDP (normuramyldipeptide) analogues modified at the C-terminus post of the molecule by a formation of an ester bond between the carboxylic group of isoglutamine and the hydroxyl function of the respective derivatives of 4-carboxamideacridine/9-acridone or 1-nitro-9-hydroxyalkylaminoacridines were synthesized as potential anticancer agents. The compounds O-(1-O-benzyl-N-acetyl-muramyl-L-alanyl-D-gamma-isoglutaminyl)-9-(ethylamino)-1-nitroacridine ester 3j and O-(1-O-benzyl-N-acetyl-muramyl-L-alanyl-D-gamma-isoglutaminyl)-9-propylamino-l-nitroacridine ester 3k exhibited high in vitro cytotoxic activity against a panel of human cell lines, prostate cancer and AIDS-related lymphoma (ARL). Analogue 3j was also active in vivo in the hollow fiber assay. Antitumor activity of both compounds were tested in vivo against difference human tumor xenograft, but only analogue 3k showed in vivo activity against se UACC-62 melanoma in mice.
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页码:183 / 189
页数:7
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