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2014 , Vol. 34 >Issue 8: 1603 - 1608

DOI: https://doi.org/10.6023/cjoc201403046

研究论文

PKC-412卤代衍生物的合成及细胞毒活性研究

  • 王立平 ,
  • 庄以彬 ,
  • 孙坤来 ,
  • 朱伟明
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  • 中国海洋大学医药学院 海洋药物教育部重点实验室 青岛 266003

收稿日期: 2014-03-20

  修回日期: 2014-04-12

  网络出版日期: 2014-05-05

基金资助

国家重点基础研究发展计划（No.2010CB833804）、国家自然科学基金（Nos.41376148，21172204，30572246）和高科技发展计划（Nos.2013AA092901，2012AA092104，2007AA091502）资助项目.

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Synthesis and Cytotoxicity of Halogenated Derivatives of PKC-412

  • Wang Liping ,
  • Zhuang Yibin ,
  • Sun Kunlai ,
  • Zhu Weiming
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  • Key Laboratory of Marine Drugs, Ministry of Education of China, School of Medicine and Pharmacy, Ocean University of China, Qingdao 266003

Received date: 2014-03-20

  Revised date: 2014-04-12

  Online published: 2014-05-05

Supported by

Project supported by the National Basic Research Program of China (No. 2010CB833804), the National Natural Science Foundation of China (Nos. 41376148, 21172204, 30572246), and the National High-Tech R&D Program of China (Nos. 2013AA092901, 2012AA092104, 2007AA091502).

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摘要

从海洋微生物发酵产物十字孢碱出发，合成12个新的PKC-412卤代衍生物1～12，其结构经1H NMR，13C NMR，IR和HRESIMS确定. 用噻唑蓝（MTT）法测定了12个卤代衍生物对肿瘤细胞株HL-60，A549和Hela的细胞毒活性. 结果表明，化合物4和10具有良好的细胞毒活性，对HL-60和A549两种肿瘤细胞株的IC50值在0.5～0.95 μmol·L-1，与PKC-412活性相当，且苯甲酰胺片段的苯环上直接卤代提高了化合物对A549细胞的选择性，值得深入研究.

关键词： 十字孢碱; PKC-412; 卤代衍生物; 肿瘤细胞毒活性

本文引用格式

王立平 , 庄以彬 , 孙坤来 , 朱伟明 . PKC-412卤代衍生物的合成及细胞毒活性研究[J]. 有机化学, 2014 , 34(8) : 1603 -1608 . DOI: 10.6023/cjoc201403046

Abstract

Twelve new halogenated derivatives of PKC-412 were synthesized from the marine microbial natural product, staurosporine. Their structures were identified by 1H NMR, 13C NMR, IR and HRESIMS. The cytotoxicities of these halogenated derivatives against HL-60, A549 and hela cell lines were evaluated using thiazolyl blue tetrazolium bromide (MTT) method. The results showed that compounds 4 and 10 displayed comparative cytotoxicity of PKC-412 against HL-60 and A549 cell lines with IC50 values of 0.5～0.95 μmol·L-1, and the halogenation on phenyl nucleus of benzamide moiety increased the selectivity of compounds to A549 cell, indicating a worth of further study.

Key words： staurosporine; PKC-412; halo-derivatives; cytotoxicity

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