Role of the side chain stereochemistry in the α-glucosidase inhibitory activity of kotalanol, a potent natural α-glucosidase inhibitor. Part 2.
Role of the side chain stereochemistry in the α-glucosidase inhibitory activity of kotalanol, a potent natural α-glucosidase inhibitor. Part 2.
复制标题
侧链立体化学在 kotalanol（一种有效的天然 α-葡萄糖苷酶抑制剂）的 α-葡萄糖苷酶抑制活性中的作用。
DOI：
10.1016/j.bmc.2012.09.006
复制
发表时间：
2012
影响因子：
3.5
通讯作者：
O. Muraoka
中科院分区：
文献类型：
--
作者：
G. Tanabe;K. Matsuoka;M. Yoshinaga;Weijia Xie;N. Tsutsui;Mumen F A Amer;Shinya Nakamura;I. Nakanishi;Xiao;M. Yoshikawa;O. Muraoka
为了研究从网状Salacia reticulata （Salacia reticulata）中分离出的天然α-葡萄糖苷酶抑制剂kotalanol(2)的侧链对抑制活性的作用，我们合成并评价了4个侧链C-4 '位置上具有反向构型(S)的非对映体（11a-11d）。其中两个（11b和11d）对麦芽糖酶和蔗糖酶的抑制活性明显丧失，而另外两个（11a和11c）在相当程度上保持了抑制活性，对5′和6′位置羟基立体化学的变化表现出明显的活性。参考这些抑制剂与hNtMGAM的硅对接研究，不同的活性被合理化。对异麦芽糖酶，4种类似物均表现出较强的抑制活性，11b和11d表现出选择性。
To examine the role of the side chain of kotalanol (2), a potent natural α-glucosidase inhibitor isolated from Salacia reticulata, on inhibitory activity, four diastereomers (11a–11d) with reversed configuration (S) at the C-4′ position in the side chain were synthesized and evaluated. Two of the four (11b and 11d) significantly lost their inhibitory activity against both maltase and sucrase, while the other two (11a and 11c) sustained the inhibitory activity to a considerable extent, showing distinct activity in response to the change of stereochemistry of the hydroxyls at the 5′and 6′ positions. Different activities were rationalized with reference to in silico docking studies on these inhibitors with hNtMGAM. Against isomaltase, all four analogs showed potent inhibitory activity as well as 2, and 11b and 11d exhibited enzyme selectivity.