Safaa P. Bahnam, Mahmood H. M. Jasim, Ahmed A. J. Mahmood
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引用次数: 0
摘要
细菌对β-内酰胺类抗生素的耐药性越来越强。降低这种耐药性的一种方法是将β-内酰胺酶抑制剂与β-内酰胺类抗生素联合使用。因此,迫切需要创新的β-内酰胺酶抑制剂。因此,本研究的目的是设计和对接两个新的酰胺系列和环和非环硼酸衍生物的希夫碱,从两个不同类别的β-内酰胺酶的四个亚型。对所设计化合物的药代动力学谱进行了计算机预测。结果显示,当与4种现有的β-内酰胺酶抑制剂(clavulanic acid, sulbactam, tazobactam and vaborbactam)匹配时,82种化合物中有15种可能增强活性。这15种化合物与所有酶活性位点的残基均表现出良好的对接作用。预测的药代动力学特性也表明这15种化合物是有前景的口服药物。所设计的化合物与4个β-内酰胺酶晶体结构的对接结果表明,它们具有作为β-内酰胺酶抑制剂的潜力。15种化合物的药代动力学特征也很有前景,使它们适合用于合成和体外测试。
IN SILICO STUDY OF NEW SCHIFF BASE-AND AMIDE-BORONIC ACID DERIVATIVES AS POTENTIAL INHIBITORS OF Β-LACTAMASES
Bacteria are becoming more and more resistant to β-lactam antibiotics. One approach to lower such resistance involves combining inhibitors of β-lactamase with β-lactams antibiotics. As such, the need for innovative inhibitors of β-lactamases is urgent. therefore, the aim of this research was to design and dock two new series of amides and Schiff bases of the cyclic and noncyclic boronate derivatives into four subtypes from two different classes of the β-lactamase enzymes. In silico prediction of the pharmacokinetic profile of the designed compounds was also performed. the results revealed possible enhanced activity of 15 out of the 82 compounds, when matched with 4 existing β-lactamase inhibitors (clavulanic acid, sulbactam, tazobactam and vaborbactam). the 15 compounds showed favorable docking interactions with the residues in the active site of all enzymes. the predicted pharmacokinetic characteristics also showed that the 15 compounds are promising as oral agents. the designed compounds have the potential to act as inhibitors of β-lactamase as shown by their docking results on 4 β-lactamase crystal structures. the pharmacokinetic profile of 15 compounds is also promising, making them suitable candidates for synthesis and in vitro testing.