Exploiting bacterial DNA gyrase as a drug target: current state and perspectives.
Reads0
Chats0
TLDR
Known gyrase-specific drugs and toxins are reviewed and the prospects for developing new antibacterials targeted to this enzyme are assessed.Abstract:
DNA gyrase is a type II topoisomerase that can introduce negative supercoils into DNA at the expense of ATP hydrolysis. It is essential in all bacteria but absent from higher eukaryotes, making it an attractive target for antibacterials. The fluoroquinolones are examples of very successful gyrase-targeted drugs, but the rise in bacterial resistance to these agents means that we not only need to seek new compounds, but also new modes of inhibition of this enzyme. We review known gyrase-specific drugs and toxins and assess the prospects for developing new antibacterials targeted to this enzyme.read more
Citations
More filters
Journal ArticleDOI
Design, synthesis, antimicrobial screening and molecular modeling of novel 6,7 dimethylquinoxalin-2(1H)-one and thiazole derivatives targeting DNA gyrase enzyme.
TL;DR: In this article , 6,7-dimethyl-3-(2-(4-nitrophenyl)-2-oxoethyl)quinoxalin-2(1H)-one and hydrazineylidene thiazol-4-one derivatives were synthesized, and evaluated for their in vitro antimicrobial activity.
Journal ArticleDOI
Ter-Seq: A high-throughput method to stabilize transient ternary complexes and measure associated kinetics
Gopinath Chattopadhyay,Shahbaz Ahmed,Nonavinakere Seetharam Srilatha,Apana Ashok,Raghavan Varadarajan +4 more
TL;DR: A high throughput methodology called Ter-Seq is described to stabilize probable ternary complexes and measure associated kinetics using the CcdA-CcdB-GyrA14 ternARY complex as a model system and examined the effect of different parameters on the rate of rejuvenation.
Journal ArticleDOI
Synthesis, characterization in vitro antimicrobial evaluation and in silico approach of molecular docking of pyrazole based pyrimidine and pyrazolone motifs
TL;DR: It has been concluded that compounds containing electron-donating groups are found to be most active against bacterial strains while compounds having both electron-Donating as well as electron-withdrawing groups are most favorable for antifungal activity.
Journal Article
Affixes are essential tools when teaching and studying pharmacological drug classes
TL;DR: This comprehensive table consists of common affixes and roots of generic drugs that the authors have found beneficial to the study and retention of pharmacology.
Journal ArticleDOI
Green Synthesis, in-vitro Antimicrobial Evaluation, Docking, and SAR Studies of Potent Quinoline-4-Carboxylic Acids
Badvel Pallavi,Rajnish Prakash Singh,Prabhat Jha,Subhash Chander,Sankaranarayanan Murugesan,Prachi Sharma,Paritosh Shukla +6 more
TL;DR: In this article, the synthesis of quinoline-4-carboxylic acid derivatives employing completely green methods such as the use of water as solvent and of microwave irradiation for heating was described.
References
More filters
Journal ArticleDOI
DNA topoisomerases: structure, function, and mechanism.
TL;DR: Surprisingly, despite little or no sequence homology, both type IA and type IIA topoisomerases from prokaryotes and the typeIIA enzymes from eukaryotes share structural folds that appear to reflect functional motifs within critical regions of the enzymes.
Journal ArticleDOI
A Common Mechanism of Cellular Death Induced by Bactericidal Antibiotics
TL;DR: The results suggest that all three major classes of bactericidal drugs can be potentiated by targeting bacterial systems that remediate hydroxyl radical damage, including proteins involved in triggering the DNA damage response, e.g., RecA.
Journal ArticleDOI
How antibiotics kill bacteria: from targets to networks
TL;DR: The multilayered effects of drug–target interactions, including the essential cellular processes that are inhibited by bactericidal antibiotics and the associated cellular response mechanisms that contribute to killing are discussed.
Journal ArticleDOI
DNA topoisomerases and their poisoning by anticancer and antibacterial drugs.
TL;DR: This review focuses on the molecular and biochemical characteristics of topoisomerases and their inhibitors and discusses the common mechanism of action ofTopoisomerase poisons by interfacial inhibition and trapping of topisomerase cleavage complexes.
Journal ArticleDOI
Quinolone resistance from a transferable plasmid
TL;DR: Although resistance was low in wild-type strains, higher levels of quinolone resistance arose readily by mutation, suggesting that a multiresistance plasmid can speed the development and spread of resistance to these valuable antimicrobial agents.
Related Papers (5)
Type IIA topoisomerase inhibition by a new class of antibacterial agents.
Benjamin D. Bax,Pan F. Chan,Drake S. Eggleston,Drake S. Eggleston,Andrew P. Fosberry,Daniel R. Gentry,Fabrice Gorrec,Fabrice Gorrec,Ilaria Giordano,Michael M. Hann,Alan Joseph Hennessy,Martin Hibbs,Jianzhong Huang,Emma J. Jones,Jo J. Jones,Kristin K. Brown,Ceri J. Lewis,Earl May,Earl May,Martin R. Saunders,Onkar M. P. Singh,Claus Spitzfaden,Carol Shen,Anthony Shillings,Andrew J. Theobald,Alexandre Wohlkonig,Alexandre Wohlkonig,Neil D. Pearson,Michael N. Gwynn +28 more