A class of novel carboline intercalators: Their synthesis, in vitro anti-proliferation, in vivo anti-tumor action, and 3D QSAR analysis
A class of novel carboline intercalators: Their synthesis, in vitro anti-proliferation, in vivo anti-tumor action, and 3D QSAR analysis
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一类新型咔啉嵌入剂：其合成、体外抗增殖、体内抗肿瘤作用和 3D QSAR 分析。
DOI：
10.1016/j.bmc.2010.07.043
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发表时间：
2010-09-01
影响因子：
3.5
通讯作者：
Peng, Shiqi
中科院分区：
文献类型：
--
作者：
Wu, Jianhui;Li, Chunyu;Peng, Shiqi
根据DOCK评分，合成了18个抗肿瘤药物N-（3-苄氧羰基咔啉-1-基）乙基氨基酸苄酯（6a-r）。它们对5种人癌细胞系的IC_（50）值从11.1 μ M到100 μ M以上。体内抗肿瘤活性测定结果表明，5个衍生物无抗肿瘤活性，9个衍生物的抗肿瘤活性与阿糖胞苷相当，3个衍生物的抗肿瘤活性高于阿糖胞苷。紫外光谱、荧光光谱以及小牛胸腺DNA（CT DNA）的相对粘度和熔解温度的测定表明，它们的作用机理可能是DNA嵌入。N-（3-苄氧羰基咔啉-1-基）乙基氨基酸苄酯（6a-r）的三维定量构效关系分析表明，其体内抗肿瘤活性显著依赖于氨基酸残基侧链的分子静电场和空间位阻场。皇冠版权所有（C）2010由爱思唯尔有限公司出版。保留所有权利。
Based on DOCK scores 18 N-(3-benzyloxycarbonylcarboline-1-yl) ethylamino acid benzylesters (6a-r) were synthesized as anti-tumor agents. Their IC50 values against five human carcinoma cell lines ranged from 11.1 mu M to more than 100 mu M. The in vivo assay identified five derivatives of them had no antitumor action, the anti-tumor activity of nine derivatives of them equaled that of cytarabine, and the anti-tumor activity of three derivatives of them was higher than that of cytarabine. The UV and fluorescence spectra, as well as the relative viscosity and melting temperature measurements of calf thymus DNA (CT DNA) with and without the representative compound suggested that DNA intercalation could be their action mechanism. The 3D QSAR analysis of N-(3-benzyloxycarbonylcarboline-1-yl) ethylamino acid benzylesters (6a-r) revealed that their in vivo anti-tumor activity significantly depends on the molecular electrostatic and steric fields of the side chain of the amino acid residue. Crown Copyright (C) 2010 Published by Elsevier Ltd. All rights reserved.