Design, synthesis and biological evaluation of 2H-benzo[b][1,4] oxazine derivatives as hypoxia targeted compounds for cancer therapeutics
Design, synthesis and biological evaluation of 2H-benzo[b][1,4] oxazine derivatives as hypoxia targeted compounds for cancer therapeutics
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DOI：
10.1016/j.bmcl.2009.05.110
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发表时间：
2009-08-01
影响因子：
2.7
通讯作者：
Mani, Sridhar
中科院分区：
文献类型：
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作者：
Das, Bhaskar C.;Madhukumar, Ankanahlli V.;Mani, Sridhar
合成了一个2 H-苯并[B][1，4]恶嗪衍生物的小库，并在常氧和低氧条件下对HepG 2细胞进行了生物活性测试。从初步筛选中，我们发现化合物10和11特异性地抑制缺氧癌细胞生长，IC 50分别为87 +/-1.8 μ M和10 +/-3.7 μ M，而保留“常氧”细胞，IC 50分别> 600 μ M和> 1 mM（不适用）。检测10对MTT、克隆形成和缺氧诱导基因的影响。MTT与克隆形成测定相关，最重要的是化合物10适当地下调缺氧诱导基因（HIF-1 α、P21和VEGF）。我们正在探索恶嗪衍生物化合物对缺氧肿瘤细胞作用的分子机制。(C)2009爱思唯尔有限公司保留所有权利。
A small library of 2H-benzo[b][1,4] oxazine derivative was synthesized and their biological activity was tested on HepG2 cells under normoxic and hypoxic conditions. From preliminary screening, we found compound 10 and 11 specifically inhibit hypoxic cancer cell growth IC50 87 +/- 1.8 mu M and IC50 10 +/- 3.7 mu M while sparing 'normoxic' cells IC50 > 600 M and > 1 mM (not applicable), respectively. We tested the effect of 10 on MTT, clonogenic and hypoxia induced genes. The MTT correlates with clonogenic assays and most importantly compound 10 down regulates hypoxia induces genes (HIF-1 alpha, P21 and VEGF) appropriately. We are in the process to explore the molecular mechanism of action of oxazine derivative compounds on hypoxia tumor cells. (C) 2009 Elsevier Ltd. All rights reserved.