PDF(Pubmed)
Abstract：
Two bisoprolol derivatives, N-acetyl bisoprolol and N-formyl bisoprolol, belonging to the beta-blocker class of antihypertensive drugs, were synthesized using acetylation and formylation reactions. The yields of the reactions were determined to be 32.40% for N-acetyl bisoprolol and 20.20% for N-formyl bisoprolol. In silico methods such as molecular docking, molecular dynamics simulation and SwissADME prediction were employed to evaluate the potential of these bisoprolol derivatives as antihypertensive drugs. These methods were used to assess the interaction between the bisoprolol derivatives and various receptors associated with hypertension, including human angiotensin I-converting enzyme (PDB ID: 1O8A), renin (PDB ID: 2V0Z), beta-1 adrenergic receptors (PDB ID: 4BVN, 7BVQ), voltage-dependent L-type calcium channel subunit alpha-1S (PDB ID: 6JP5) and mineralocorticoid receptor (PDB ID: 6L88). Our results demonstrated the highest binding energy when bisoprolol and its derivatives bound to 4BVN, with binding energy values of 6.74 kcal mol-1, 7.03 kcal mol-1 and 7.63 kcal mol-1 for bisoprolol, N-acetyl bisoprolol and N-formyl bisoprolol, respectively. The stability of these complexes was confirmed by molecular dynamics simulations, with a root-mean-square deviation value of approximately 2. Furthermore, the SwissADME results indicated that both derivatives exhibited similar properties to the reference drug bisoprolol.
摘要：
两种比索洛尔衍生物，N-乙酰基比索洛尔和N-甲酰比索洛尔，属于β受体阻滞剂类的抗高血压药物，使用乙酰化和甲酰化反应合成。确定反应的产率对于N-乙酰基比索洛尔为32.40%,对于N-甲酰基比索洛尔为20.20%。在硅方法如分子对接，使用分子动力学模拟和SwissADME预测来评估这些比索洛尔衍生物作为抗高血压药物的潜力。这些方法用于评估比索洛尔衍生物与与高血压相关的各种受体之间的相互作用。包括人血管紧张素I转换酶（PDBID：1O8A），肾素（PDBID：2V0Z），β-1肾上腺素能受体（PDBID：4BVN，7BVQ)，电压依赖性L型钙通道亚基α-1S（PDBID：6JP5）和盐皮质激素受体（PDBID：6L88）。我们的结果表明，当比索洛尔及其衍生物与4BVN结合时，结合能最高，比索洛尔的结合能值为6.74kcalmol-1，7.03kcalmol-1和7.63kcalmol-1，N-乙酰基比索洛尔和N-甲酰比索洛尔，分别。分子动力学模拟证实了这些配合物的稳定性,均方根偏差值大约为2。此外，SwissADME结果表明两种衍生物表现出与参比药物比索洛尔相似的性质。
