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从内生种筛选新德里金属β-内酰胺酶-1 抑制剂

and screening of new Delhi metallo-β-lactamase-1 inhibitors from endophytic spp.

机构信息

Centre for Research in Infectious Diseases (CRID), School of Chemical and Biotechnology (SCBT), SASTRA Deemed University, Tirumalaisamudram, Thanjavur, Tamil Nadu, India.

Computational Molecular Biophysics Laboratory (CMBL), School of Chemical and Biotechnology (SCBT), SASTRA Deemed University, Tirumalaisamudram, Thanjavur, Tamil Nadu, India.

出版信息

J Biomol Struct Dyn. 2022;40(24):13593-13605. doi: 10.1080/07391102.2021.1990132. Epub 2021 Oct 16.

Abstract

The increase in drug resistance over the last two decades is a big threat in health care settings. More importantly, the dissemination of carbapenem-resistant Enterobacteriaceae is the major threat to public health with an increase in morbidity and mortality. β-lactamase is known to confer enteric bacteria with nearly complete resistance to all β-lactam antibiotics including the late-generation carbapenems. The commercially available β-lactamase inhibitors, clavulanic acid, sulbactam, and tazobactam are being met with an increasing number of resistant phenotypes and are ineffective against pathogens harbouring New Delhi metallo--lactamase (NDM-1). Inhibition of New Delhi metallo--lactamase-1 activity is one potential way to treat metallo β-lactamase (MBL) producing multi drug resistant (MDR) pathogen. The present study focused on screening of New Delhi metallo--lactamase-1 (BLIs) from endophytic spp. using and methods. The study identified three potential inhibitors of New Delhi metallo--lactamase-1, namely dodecanoic acid, dl-alanyll-leucine and phenyl propanedioic acid. These molecules were found to bind to other MBLs namely, IMP-1 and VIM-2. To the best of our knowledge, this is the first kind of study reporting the binding mode of these molecules with New Delhi metallo--lactamase-1.Communicated by Ramaswamy H. Sarma.

摘要

在过去的二十年中,药物耐药性的增加是医疗保健环境中的一大威胁。更重要的是,碳青霉烯类耐药肠杆菌科的传播是对公众健康的主要威胁,导致发病率和死亡率上升。β-内酰胺酶使肠道细菌对几乎所有β-内酰胺抗生素(包括最新一代的碳青霉烯类抗生素)产生完全耐药性。市售的β-内酰胺酶抑制剂克拉维酸、舒巴坦和他唑巴坦正面临越来越多的耐药表型,对携带新德里金属β-内酰胺酶(NDM-1)的病原体无效。抑制新德里金属β-内酰胺酶-1 的活性是治疗金属β-内酰胺酶(MBL)产生的多药耐药(MDR)病原体的一种潜在方法。本研究重点使用 和 方法从内生 spp 中筛选新德里金属β-内酰胺酶-1(BLIs)。该研究鉴定了三种新德里金属β-内酰胺酶-1 的潜在抑制剂,即十二烷酸、dl-丙氨酰-亮氨酸和苯丙二酸。这些分子被发现与其他 MBLs,即 IMP-1 和 VIM-2 结合。据我们所知,这是首次报道这些分子与新德里金属β-内酰胺酶-1 的结合模式的研究。由 Ramaswamy H. Sarma 通讯。

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