Docking and SAR studies of salacinol derivatives as α-glucosidase inhibitors
Docking and SAR studies of salacinol derivatives as α-glucosidase inhibitors
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DOI：
10.1016/j.bmcl.2010.06.059
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发表时间：
2010-08-01
影响因子：
2.7
通讯作者：
Nakanishi, Isao
中科院分区：
文献类型：
--
作者：
Nakamura, Shinya;Takahira, Kazunori;Nakanishi, Isao
Salacinol是从Salacia reticulata中分离的一种有效的α-葡萄糖苷酶抑制剂，也是一种良好的抗糖尿病药物的先导化合物。阐明水杨酚与α-葡萄糖苷酶的结合状态对于基于结构的药物设计的有效优化研究至关重要。两个抑制剂，阿卡波糖和藜芦碱，其复杂的结构是已知的，重新对接模拟进行，以确保适当的对接位姿预测。模拟准确地再现了两种实验结合状态。然后，使用相同的模拟协议，水杨酸及其衍生物的结合模式进行了预测。Salacinol与蛋白质的结合模式与藜芦碱相似，预测的结构可以解释大多数Salacinol衍生物的构效关系。(C)2010爱思唯尔有限公司版权所有。
Salacinol is a potent alpha-glucosidase inhibitor isolated from Salacia reticulata, and a good lead compound for an antidiabetic drug. It is essential to clarify the binding state of salacinol to alpha-glucosidase for efficient optimization study using structure-based drug design. Redocking simulations of two inhibitors, acarbose and casuarine whose complex structures are known, were performed to assure the appropriate docking pose prediction. The simulation reproduced both experimental binding states with accuracy. Then, using the same simulation protocol, the binding mode of salacinol and its derivatives has been predicted. Salacinol bound to the protein with a similar binding mode as casuarine, and the predicted structures could explain most of the structure-activity relationships of salacinol derivatives. (C) 2010 Elsevier Ltd. All rights reserved.