Recent progress in the discovery and development of DNA gyrase B inhibitors

Barančokova, Michaela (author), Kikelj, Danijel (author), Ilaš, Janez (author)

New antibacterials that modulate less explored targets are needed to fight the emerging bacterial resistance. DNA gyrase and topoisomerase IV are attractive targets in this search. These are both type II topoisomerases that can cleave both DNA strands, and can thus alter DNA topology during replication or similar processes. Currently, there are no ATP-competitive inhibitors of these two enzymes on the market, as the only aminocoumarin representative, novobiocin, was withdrawn due to safety concerns. The search for novel ATP-competitive inhibitors is a focus of ongoing industrial and academical research. This review summarizes the recent efforts in the design, synthesis and evaluation of GyrB/ParE inhibitors. The various approaches to achieve improved antibacterial activities are described, with particular reference to Gram-negative bacteria.

• Language: English
• Keywords: antibacterial, ATP-competitive, DNA gyrase, drug discovery, Gram-negative bacteria, GyrB, inhibitor, Par, topoisomerase II, topoisomerase IV
• Work type: Scientific work
• Typology: 1.02 - Review Article
• Organization: FFA - Faculty of Pharmacy
• Publication status: Published
• Publication version: Author Accepted Manuscript
• Year: 2018
• Numbering: Vol. 10, no. 10
• PID: 20.500.12556/RUL-106641
• UDC: 615.015.8
• ISSN on article: 1756-8919
• DOI: 10.4155/fmc-2017-0257
• COBISS.SI-ID: 4515441
• Publication date in RUL: 09.03.2019

Record is a part of a journal

• Title: Future medicinal chemistry
• Publisher: Future Science
• ISSN: 1756-8919
• COBISS.SI-ID: 3730289

Secondary language

• Language: Slovenian
• Keywords: zaviralci giraze B, topoizomeraza IV, akademske raziskave

Projects

• Funder: EC - European Commission
• Funding programme: H2020
• Project number: 642620
• Name: Interdisciplinary Training Network for Validation of Gram-Negative Antibacterial Targets
• Acronym: INTEGRATE