Photoswitchable anticancer activity via trans-cis isomerization of a combretastatin A-4 analog.
Photoswitchable anticancer activity via trans-cis isomerization of a combretastatin A-4 analog.
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DOI：
10.1039/c5ob02005k
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发表时间：
2016-01-07
影响因子：
3.2
通讯作者：
Hartman MC
中科院分区：
文献类型：
--
作者：
Sheldon JE;Dcona MM;Lyons CE;Hackett JC;Hartman MC
考布他汀A-4（CA 4）是一种高效的抗癌药物，其作为微管蛋白聚合的抑制剂。CA 4结构的核心含有顺式芪，并且已知反式异构体的效力明显较低。我们制备了CA 4的偶氮苯类似物（Azo-CA 4），其在光照下显示出13-35倍的效力增强。光照下的EC 50值在中nM范围内。由于其热还原为毒性较低的反式的能力，Azo-CA 4也具有随时间自动关闭其活性的能力。Azo-CA 4的效力低于CA-4，因为它在谷胱甘肽的存在下降解，如UV-Vis光谱和ESI-MS所证明的。然而，Azo-CA 4代表了用于治疗癌症的可转换效力的有希望的策略。
Combretastatin A-4 (CA4) is highly potent anticancer drug that acts as an inhibitor of tubulin polymerization. The core of the CA4 structure contains a cis-stilbene, and it is known that the trans isomer is significantly less potent. We prepared an azobenzene analog of CA4 (Azo-CA4) that shows 13–35 fold enhancement in potency upon illumination. EC50 values in the light were in the mid nM range. Due to its ability to thermally revert to less toxic trans form, Azo-CA4 also has the ability to automatically turn its activity off with time. Azo-CA4 is less potent than CA-4 because it degrades in the presence of glutathione as evidenced by UV-Vis spectroscopy and ESI-MS. Nevertheless, Azo-CA4 represents a promising strategy for switchable potency for treatment of cancer.