当前位置: X-MOL 学术Pharm. Chem. J. › 论文详情
Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)
Exploitation of Pare Topoisomerase IV as Drug Target for the Treatment of Multidrug-Resistant Bacteria: A Review
Pharmaceutical Chemistry Journal ( IF 0.9 ) Pub Date : 2020-08-01 , DOI: 10.1007/s11094-020-02223-w
Vidyasrilekha Yele , Afzal Azam Md

The antibacterial resistance (ABR) is a growing phenomenon and global threat to mankind. To circumvent the ABR, many approaches have been put forth, but none of them meet the pre-requisites associated with the resistance mechanisms. In this review, we focused on the importance of unexploited enzyme, ParE, a topoisomerase responsible for the bacterial survival. The bacterial topoisomerases maintain the topological state of DNA. The gyrases and topoisomerases IV are validated targets for the antibacterial activity. Both these enzymes are structurally similar and possess high degree conservation in the catalytic domain of the N-terminal region, which make them appealing targets for broad spectrum antibacterial activity. Despite being an attractive target for the development of new antibacterials, there are currently no antibiotics targeting gyrases and topoisomerase (topo) IV in the market. Availability of the high-resolution crystal structure data for ParE made it possible to design new classes of antibacterials. Here, we discuss the importance of targeting topo IV enzyme as it is less prone to bacterial resistance which has been disclosed in the literature.

中文翻译:

Pare拓扑异构酶IV作为治疗多重耐药菌的药物靶点的开发:综述

抗菌素耐药性(ABR)是一种日益严重的现象,对人类构成全球威胁。为了规避 ABR,已经提出了许多方法,但没有一种方法满足与耐药机制相关的先决条件。在这篇综述中,我们专注于未开发的酶 ParE 的重要性,ParE 是一种负责细菌存活的拓扑异构酶。细菌拓扑异构酶维持 DNA 的拓扑状态。促旋酶和拓扑异构酶 IV 是抗菌活性的验证靶标。这两种酶在结构上相似,并且在 N 端区域的催化域中具有高度保守性,这使它们成为广谱抗菌活性的有吸引力的目标。尽管是开发新抗菌药物的有吸引力的目标,目前市场上没有针对旋转酶和拓扑异构酶 (topo) IV 的抗生素。ParE 的高分辨率晶体结构数据的可用性使得设计新类别的抗菌剂成为可能。在这里,我们讨论了靶向 topo IV 酶的重要性,因为它不太容易出现文献中公开的细菌耐药性。
更新日期:2020-08-01
down
wechat
bug