Tumskiy Roman S, Tumskaia Anastasiia V, Pylaev Timophey E, Avdeeva Elena S, Evstigneeva Stella S
Institute of Biochemistry & Physiology of Plants & Microorganisms, Russian Academy of Sciences, 13 Prospekt Entuziastov, Saratov, 410049, Russia.
Chemistry Institute, Saratov State University, 83 Astrakhanskaya, Saratov, 410012, Russia.
Future Med Chem. 2021 Jun;13(12):1041-1055. doi: 10.4155/fmc-2021-0020. Epub 2021 Apr 29.
Antibiotic resistance, which occurs through the action of metallo-β-lactamases (NDM-1), is a serious problem in the treatment of infectious diseases. Therefore, the discovery of new NDM-1 inhibitors and promising antibacterial agents as inhibitors of alternative targets (MetAP-1) is important. In this study, a virtual library of 5-arylidene barbituric acids was created and molecular docking was performed for identification of novel possible inhibitors of NDM-1 and MetAP-1. Antibacterial activity (agar well-diffusion assay) and cytotoxicity (alamarBlue assay) of perspective compounds were evaluated. Pharmacokinetic profiles and molecular properties were predicted. We have identified possible novel inhibitors of NDM-1 and MetAP-1 with bacteriostatic activity, most of which are not cytotoxic and have potential excellent drug-likeness properties.
通过金属β-内酰胺酶（NDM-1）的作用产生的抗生素耐药性是传染病治疗中的一个严重问题。因此，发现新的NDM-1抑制剂以及作为替代靶点（MetAP-1）抑制剂的有前景的抗菌剂很重要。在本研究中，创建了一个5-亚芳基巴比妥酸虚拟库，并进行了分子对接以鉴定NDM-1和MetAP-1的新型潜在抑制剂。评估了有前景化合物的抗菌活性（琼脂孔扩散试验）和细胞毒性（alamarBlue试验）。预测了药代动力学特征和分子性质。我们已经鉴定出了具有抑菌活性的NDM-1和MetAP-1的潜在新型抑制剂，其中大多数没有细胞毒性且具有潜在的优异类药性质。
