Isolation, semisynthesis, covalent docking and transforming growth factor beta-activated kinase 1 (TAK1)-inhibitory activities of (5Z)-7-oxozeaenol analogues.
Isolation, semisynthesis, covalent docking and transforming growth factor beta-activated kinase 1 (TAK1)-inhibitory activities of (5Z)-7-oxozeaenol analogues.
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DOI：
10.1016/j.bmc.2015.09.037
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发表时间：
2015-11-01
影响因子：
3.5
通讯作者：
Croatt MP
中科院分区：
文献类型：
--
作者：
Fakhouri L;El-Elimat T;Hurst DP;Reggio PH;Pearce CJ;Oberlies NH;Croatt MP
分离和筛选了(5Z)-7-氧代玉米醇及其类似物，以探讨其作为TAK1抑制剂的活性。合成了7个类似物，分离出了20多种天然产物，考察了分子的不同区域对TAK1抑制的作用。合成了一种新型的非芳香族二氟衍生物，其活性与铅相近。这是这类化合物中第一个具有TAK1抑制作用的例子。对分离和合成的类似物进行了共价对接，发现观察到的活性与计算的结合量之间存在很强的相关性。
(5Z)-7-Oxozeanol and related analogues were isolated and screened to explore their activity as TAK1 inhibitors. Seven analogues were synthesized and more than a score of natural products isolated that examined the role that different areas of the molecule contribute to TAK1 inhibition. A novel nonaromatic difluoro-derivative was synthesized that had similar potency compared to the lead. This is the first example of a nonaromatic compound in this class to have TAK1 inhibition. Covalent docking for the isolated and synthesized analogues was carried out and found a strong correlation between the observed activities and the calculated binding.