Recent updates of fluoroquinolones as antibacterial agents

Abstract

Fluoroquinolones remain one of the most important kind of antibacterial agents used nowadays. The emergence of more virulent and resistant strains of bacteria by the development of either mutated DNA-binding proteins or efflux pump mechanism for drugs is considered the main problem associated with the therapeutic use of these drugs. This situation participated in pushing researchers to design new fluoroquinolone derivatives, mainly with different substituents at C-7 to withstand these resistant strains of bacteria and to obtain a wider spectrum of activity including activity against anaerobic organisms. Conjugation of fluoroquinolones with substitutions such as 1,2,4-triazoles, alkyl oximes, flavonoids, aryl furans, benzofuroxans, metronidazoles or even other antibiotics such as neomycin-B produced derivatives that have a superior and wider spectrum of activity and better resistance than the classical fluoroquinolone agents. Addition of a hydroxamic acid moiety to fluoroquinolones also increased the activity against Proteus mirabilis, which represents one of the most resistant strains of bacteria in urinary tract infections. This review aims to highlight the recent updates made for fluoroquinolones for broadening the spectrum of activity to become active not only against resistant strains of bacteria but also against anaerobic pathogens.

The challenge of intracellular antibiotic accumulation, a function of fluoroquinolone influx versus bacterial efflux

“…FQ generations 2, 3, and 4, exhibit similar structures that differ only in the substituents at R 1 , R 7 , and R 8 of the quinolone core. R 1 , R 7 , and R 8 substituents appear the key factors for penetration and target binding for which new compounds are developed 39,40 . N1 cyclopropyl and R 8 unsubstituted seemed to be related to high SICAR IN .…”

“…All the tested FQs have a C7-piperazine group except PAZ. This moiety has been shown to increase the drugs' ability to pass the bacterial membrane resulting in enhanced activity 40 . Piperazine substitutions in studied FQs do not alter SICAR IN , although it has been reported that numerous changes in piperazine moiety can affect the activity of the drug 13 .…”

Quinolone derivatives and their antifungal activities: An overview

“…4‐Quinolones, which are exemplified by fluoroquinolones, have been applied in clinics for the treatment of urinary infections in humans since the discovery of nalidixic acid in 1962 . Currently, 4‐quinolone antibiotics are the second largest used drugs in anti‐infective chemotherapy, and they also play a pivotal role in the development of new drugs.…”

Antibacterial and Urease Inhibitory activity of New Piperazinyl N-4 Functionalized Ciprofloxacin-oxadiazoles

“…[4,[6][7][8] Moreover, many derivatives with promising activity were prepared, including candidates that reached clinical investigations. [9][10][11][12] Chemical modifications at C3 and C7 of typical quinolone scaffold have the greatest influence on their activity [13], where position 7 largely affects activity, access and direction toward different molecular targets. [14][15][16][17][18] Moreover, introducing bulky groups at C7 was reported to broaden the spectrum of antibacterial activity and reduce the likelihood of developing resistance.…”