Ghabbour Hazem A, El-Bendary Eman R, El-Ashmawy Mahmoud B, El-Kerdawy Mohamed M
Department of Medicinal Chemistry, Faculty of Pharmacy, Mansoura University, Mansoura 35516, Egypt.
Molecules. 2014 Mar 20;19(3):3417-35. doi: 10.3390/molecules19033417.
A new series of oxime ethers 4a-z was designed and synthesized to test the blocking activity against β₁ and β₂-adrenergic receptors. Docking of these ether derivatives into the active site of the identified 3D structures of β₁ and β₂-adrenergic receptors showed MolDock scores comparable to those of reference compounds. Biological results revealed that the inhibition effects on the heart rate and contractility are less than those of propranolol. Nevertheless, the two compounds 4p and 4q that displayed the highest negative MolDock score with β₂-adrenergic receptors showed β₂-antagonistic activity by decreasing salbutamol relaxation of precontracted tracheal strips, which indicates the importance of a chlorothiophene moiety in the hydrophobic region for best complementarity with β₂ receptors. On other hand, the presence of a homoveratryl moiety increases the MolDock score of the tested compounds with the β₁ receptor.
设计并合成了一系列新的肟醚4a - z,以测试其对β₁和β₂肾上腺素能受体的阻断活性。将这些醚衍生物对接至已确定的β₁和β₂肾上腺素能受体的三维结构活性位点,结果显示其MolDock评分与参考化合物相当。生物学结果表明,它们对心率和收缩性的抑制作用小于普萘洛尔。然而,与β₂肾上腺素能受体显示出最高负MolDock评分的两种化合物4p和4q,通过降低沙丁胺醇对预收缩气管条的舒张作用而表现出β₂拮抗活性,这表明疏水区域中的氯噻吩部分对于与β₂受体的最佳互补性很重要。另一方面,高藜芦基部分的存在增加了测试化合物与β₁受体的MolDock评分。