Abstract
The quinolone antibiotics arose in the early 1960s, with the first examples possessing a narrow-spectrum of activity with unfavorable pharmacokinetic properties. Over time, the development of new quinolone antibiotics has led to improved analogues with an expanded spectrum and high efficacy. Nowadays, quinolones are widely used for treating a variety of infections. Quinolones are broad-spectrum antibiotics that are active against both Gram-positive and Gram-negative bacteria, including mycobacteria, and anaerobes. They exert their actions by inhibiting bacterial nucleic acid synthesis through disrupting the enzymes topoisomerase IV and DNA gyrase, and by causing breakage of bacterial chromosomes. However, bacteria have acquired resistance to quinolones, similar to other antibacterial agents, due to the overuse of these drugs. Mechanisms contributing to quinolone resistance are mediated by chromosomal mutations and/or plasmid gene uptake that alter the topoisomerase targets, modify the quinolone, and/or reduce drug accumulation by either decreased uptake or increased efflux. This review discusses the development of this class of antibiotics in terms of potency, pharmacokinetics and toxicity, along with the resistance mechanisms which reduce the quinolones' activity against pathogens. Potential strategies for future generations of quinolone antibiotics with enhanced activity against resistant strains are suggested.
Highlights
The quinolones are a family of antibiotics containing a bicyclic core structure related to the compound 4-quinolone (Fig. 1).[1]
A 2015 perspective that examined the origins of quinolone antibiotics in greater detail points out that the author of the 1962 publication (George Lesher) described the isolation of-chloro-1-ethyl-1,4dihydro-4-oxo-3-quinolinecarboxylic acid in the late 1950s as a by-product of chloroquine synthesis, with modest antibacterial activity leading to further work on analogues, including nalidixic acid.[1]
Nalidixic acid is a narrow-spectrum agent against enteric bacteria used for treating uncomplicated urinary tract infections (UTIs).[4]
Summary
The quinolones are a family of antibiotics containing a bicyclic core structure related to the compound 4-quinolone (Fig. 1).[1]. MedChemComm enzymes that regulate the chromosomal supercoiling required for DNA synthesis.[9] Over time, quinolone resistance has become a serious problem among many emerging resistant pathogens.[10] The mutations generated by the bacteria against quinolones are generally located on the target enzyme binding sites in DNA gyrase and topoisomerase IV.[11] In addition, resistance to this class of antibiotics can be obtained by acquisition of a resistant plasmid from other sources in the environment through horizontal transfer, leading to the rapid spread of resistance.[12]. This review discusses the current knowledge of the development process of quinolones on how structural modifications in the evolving generations have mediated improvements in terms of potency, pharmacokinetics, and toxicity. It summarizes the relevant knowledge of mode of actions and resistance. The review examines future strategies to improve the activity of this class and overcome the resistance
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
