Synthesis and Biological Evaluation of Novel Water-Soluble Poly-(ethylene glycol)-10-hydroxycamptothecin Conjugates.
Synthesis and Biological Evaluation of Novel Water-Soluble Poly-(ethylene glycol)-10-hydroxycamptothecin Conjugates.
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DOI：
10.3390/molecules20059393
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发表时间：
2015-05-21
期刊：
影响因子：
--
通讯作者：
Yu P
中科院分区：
文献类型：
--
作者：
Guo N;Jiang D;Wang L;You X;Teng YO;Yu P
为了提高10-羟基喜树碱（HCPT）的抗肿瘤活性和水溶性，通过缬氨酸间隔基将聚乙二醇（PEG）与HCPT的10-羟基缀合，设计并合成了一系列新型HCPT缀合物。在 37°C、pH 7.4 缓冲液中测定了这些合成化合物的体外稳定性，结果表明它们以不同的速率释放 HCPT。所有化合物均在体外对 K562、HepG2 和 HT-29 细胞表现出显着的抗肿瘤活性。其中，化合物4a、4d、4e和4f的效力比HCPT高2-5倍。研究发现这些缀合物的稳定性和抗肿瘤活性与PEG的长度和连接体类型密切相关，具有相对短的PEG链和氨基甲酸酯键的缀合物（化合物4a和4f）表现出HCPT的控释和优异的体外抗肿瘤活性。
In order to improve the antitumor activity and water solubility of 10-hydroxycamptothecin (HCPT), a series of novel HCPT conjugates were designed and synthesized by conjugating polyethylene glycol (PEG) to the 10-hydroxyl group of HCPT via a valine spacer. The in vitro stability of these synthesized compounds was determined in pH 7.4 buffer at 37 °C, and the results showed that they released HCPT at different rates. All the compounds demonstrated significant antitumor activity in vitro against K562, HepG2 and HT-29 cells. Among them, compounds, 4a, 4d, 4e and 4f, exhibited 2–5 times higher potency than HCPT. The stability and antitumor activity of these conjugates were found to be closely related to the length of PEG and the linker type, conjugates with a relatively short PEG chain and carbamate linkages (compounds 4a and 4f) exhibited controlled release of HCPT and excellent antitumor in vitro activity.
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