[2,3-裂环三萜烯酸单酰胺和二酰胺的合成及其生物活性]

[Synthesis and biological activity of 2,3-secotriterpene acid mono- and diamides].

作者信息

Tolmacheva I A, Igosheva E V, Vikharev Iu B, Grishko V V, Savinova O V, Boreko E I, Eremin V F

出版信息

Bioorg Khim. 2013 Mar-Apr;39(2):212-20. doi: 10.1134/s1068162013020143.

DOI:10.1134/s1068162013020143

Abstract

Four types of amide (C3; C28; C3-C28) conjugates based on 2,3-seco-18alphaH-oleanane and 2,3-secolupane mono- and dicarboxylic acids were synthesized. The range of diamide derivatives was supplemented with C3-C3' and C28-C28' dicondensed amides with two A-secotriterpene backbones educed by reacting monocarboxylic A-secoacids with biogenic amino acid lysine. Compounds with inhibitory action against herpes virus reproduction (EC50 8.7 and 4.1 McM) were found among the synthesized mono- and diamide derivatives containing an ethyl-beta-alaninate fragment. It has been ascertained that diamide with ethyl-beta-alaninate fragment combines anti-herpes virus properties and anti-HIV activity (EC50 5.1 McM). For active compounds, the maximum non-toxic concentration (MNTC)/EC50 ratios ranges from 9.7 to 40.8. The synthesized amide conjugates do not exhibit any marked cytotoxic effects against human tumor cell lines rabdomiosarcoma RD TE32, A549 lung carcinoma and melanoma MS.

摘要

合成了基于2,3-断-18αH-齐墩果烷和2,3-断羽扇豆烷单羧酸和二羧酸的四种酰胺（C3；C28；C3-C28）共轭物。通过使单羧酸A-断酸与生物源氨基酸赖氨酸反应得到的具有两个A-断三萜骨架的C3-C3'和C28-C28'二缩合酰胺补充了二酰胺衍生物的范围。在含有β-丙氨酸乙酯片段的合成单酰胺和二酰胺衍生物中发现了对疱疹病毒复制具有抑制作用的化合物（EC50为8.7和4.1μM）。已经确定，具有β-丙氨酸乙酯片段的二酰胺兼具抗疱疹病毒特性和抗HIV活性（EC50为5.1μM）。对于活性化合物，最大无毒浓度（MNTC）/EC50比值在9.7至40.8之间。合成的酰胺共轭物对人肿瘤细胞系横纹肌肉瘤RD、TE32、A549肺癌和黑色素瘤MS没有表现出任何明显的细胞毒性作用。