Molecular characterization of the boron adducts of the proteasome inhibitor bortezomib with epigallocatechin-3-gallate and related polyphenols.
Molecular characterization of the boron adducts of the proteasome inhibitor bortezomib with epigallocatechin-3-gallate and related polyphenols.
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DOI：
10.1039/c4ob02512a
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发表时间：
2015-04-07
影响因子：
3.2
通讯作者：
Petasis NA
中科院分区：
文献类型：
--
作者：
Glynn SJ;Gaffney KJ;Sainz MA;Louie SG;Petasis NA
据报道，绿色茶多酚表没食子儿茶素-3-没食子酸酯（EGCG）可有效拮抗硼替佐米诱导癌细胞凋亡的能力。这种相互作用是由于形成的共价加合物之间的酚部分的表没食子儿茶素与硼酸基团的硼替佐米。然而，这种硼加合物的结构细节和有助于其形成的分子因素及其抑制硼替佐米活性的能力仍不清楚。本文介绍了使用核磁共振光谱和细胞测定来表征的结构和性质的硼加合物的表没食子儿茶素没食子酸酯和相关的多酚。所观察到的硼加合物包括硼酸盐和硼酸盐衍生物，其结构特征与基于细胞的评估EGCG和其他酚类拮抗Bortezelatin的抗癌活性的能力相关。BZM/EGCG加合物的增强的稳定性归因于电子和空间的原因，以及新发现的BZM的硼原子与相邻的酰胺键的分子内相互作用。报道的方法提供了一种有用的方法，用于确定多酚与硼基药物形成不希望的加合物并干扰其作用的潜在能力。
The green tea polyphenol epigallocatechin-3-gallate (EGCG) was reported to effectively antagonize the ability of Bortezomib to induce apoptosis in cancer cells. This interaction was attributed to the formation of a covalent adduct between a phenolic moiety of EGCG with the boronic acid group of Bortezomib. However, the structural details of this boron adduct and the molecular factors that contribute to its formation and its ability to inhibit Bortezomib's activity remain unclear. This paper describes the use of NMR spectroscopy and cell assays to characterize the structures and properties of the boron adducts of EGCG and related polyphenols. The observed boron adducts included both boronate and borate derivatives, and their structural characteristics were correlated with cell-based evaluation of the ability of EGCG and other phenols to antagonize the anticancer activity of Bortezomib. The enhanced stability of the BZM/EGCG adduct was attributed to electronic and steric reasons, and a newly identified intramolecular interaction of the boron atom of BZM with the adjacent amide bond. The reported approach provides a useful method for determining the potential ability of polyphenols to form undesired adducts with boron-based drugs and interfere with their actions.
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影响因子：
3
作者：
Bannerman, Bret;Xu, Ling;Jones, Matthew;Tsu, Christopher;Yu, Jie;Hales, Paul;Monbaliu, Johan;Fleming, Paul;Dick, Lawrence;Manfredi, Mark;Claiborne, Christopher;Bolen, Joseph;Kupperman, Erik;Berger, Allison
通讯作者：
Berger, Allison
影响因子：
11.2
作者：
Fels DR;Ye J;Segan AT;Kridel SJ;Spiotto M;Olson M;Koong AC;Koumenis C
通讯作者：
Koumenis C
影响因子：
2.9
作者：
Cavo, Michele
通讯作者：
Cavo, Michele
影响因子：
5.7
作者：
Cho, Hee-Yeon;Wang, Weijun;Chen, Thomas C.
通讯作者：
Chen, Thomas C.
影响因子：
11.8
作者：
Adams, J
通讯作者：
Adams, J