Pharmacognosy and Pharmaceutical Chemistry Department, Pharmacy College, Taibah University, Al-Madinah Al-Munawarah 41477, Saudi Arabia.
Molecules. 2018 May 29;23(6):1304. doi: 10.3390/molecules23061304.
A few new anthranilate diamide derivatives, ⁻, ⁻ and ⁻, were designed, synthesized, and evaluated for their inhibitory activity against two interesting antidiabetic targets, α-glucosidase and glycogen phosphorylase enzymes. Different instrumental analytical tools were applied in identification and conformation of their structures like; C NMR, ¹H NMR and elemental analysis. The screening of the novel compounds showed potent inhibitory activity with nanomolar concentration values. The most active compounds () and () showed the highest inhibitory activity against α-glucosidase and glycogen phosphorylase enzymes IC = 0.01247 ± 0.01 µM and IC = 0.01372 ± 0.03 µM, respectively. In addition, in vivo testing of the highly potent α-glucosidase inhibitor () on rats with DTZ-induced diabetes was done and showed significant reduction of blood glucose levels compared to the reference drug. Furthermore, a molecular docking study was performed to help understand the binding interactions of the most active analogs with these two enzymes. The data obtained from the molecular modeling were correlated with those obtained from the biological screening. These data showed considerable antidiabetic activity for these newly synthesized compounds.
设计、合成了几种新的邻氨基苯甲酰胺衍生物 ⁻ 、 ⁻ 和 ⁻ ，并评估了它们对两种有趣的抗糖尿病靶点（α-葡萄糖苷酶和糖原磷酸化酶）的抑制活性。不同的仪器分析工具，如 C NMR、 ¹H NMR 和元素分析，用于鉴定和构象确定其结构。新型化合物的筛选显示出具有纳摩尔浓度值的有效抑制活性。最活性的化合物（）和（）对α-葡萄糖苷酶和糖原磷酸化酶的抑制活性最高，IC = 0.01247 ± 0.01 µM 和 IC = 0.01372 ± 0.03 µM。此外，在 DTZ 诱导糖尿病大鼠中对高活性α-葡萄糖苷酶抑制剂（）进行了体内测试，与参比药物相比，血糖水平显著降低。此外，还进行了分子对接研究，以帮助了解最活性类似物与这两种酶的结合相互作用。从分子建模中获得的数据与从生物筛选中获得的数据相关联。这些数据表明这些新合成的化合物具有相当的抗糖尿病活性。
