Mouse Anti-Fluoroquinolones monoclonal antibody, clone FK2

Since the discovery of nalidixic acid, quinolones have been the focus of attention of researchers around the world and have led to the development of a series of multifunctional derivatives with different properties and multiple effects. These quinolones dominated clinical applications and are still widely used today. A new generation of quinolones with broader antimicrobial activity can be used to treat a wide range of infectious diseases as well as to address the challenge of bacterial resistance.

First-generation quinolones were approved for the treatment of urinary tract infections and sexually transmitted diseases, but were quickly withdrawn from the market due to limited therapeutic efficacy and carcinogenic side effects. In subsequent studies researchers have synthesized FQs by adding fluorine atoms at the C-6 position and cyclic diamine piperazine molecules at the C-7 position, which have wider spectrum of activity, higher potency, better oral bioavailability, enhanced pharmacokinetics, tissue penetration, and good tolerability, and have shown significant efficacy against Gram-negative, Gram-positive, and anaerobic organisms. FQs can be categorized into four generations based on pharmacokinetic profiles. The third and fourth generation of FQs, whose structures contain methoxy at the C-8 position on this basis, are now approved for the treatment of respiratory infections, including fatal tuberculosis, and the fourth-generation drugs are even effective against ciprofloxacin-resistant pneumococci.

Fluoroquinolone antibiotics (FQs) act as broad-spectrum antibacterials by targeting DNA gyrase or targeting topoisomerase II to inhibit the replication and transcription of bacterial DNA. These two enzymes are completely different in their bacterial and mammalian counterparts, so FQs are thousands of times more sensitive to bacteria. In addition to their antimicrobial effects, FQs have been found to have other functions. Researchers have found that FQs have anti-malarial efficacy, with good antimalarial potential at multiple stages of the Plasmodium life cycle. FQs also have immunomodulatory properties, the older generation of FQs can only induce cytokine synthesis at high doses, in contrast the newer generation of FQs can inhibit cytokine synthesis even at lower concentrations. The molecular mechanisms by which FQs stimulate or inhibit immunomodulatory effects are currently unknown. Based on existing studies, it has been suggested that these effects of FQs are due to interactions with transcription factors such as NFB/NFAT/AP1, modulation of intracellular levels of cyclic AMP or phosphodiesterases, and certain other unknown intracellular events. FQs are also promising anticancer drug candidates, and some of them have already entered different clinical trials. It has many desirable properties in cancer therapy, such as low toxicity, low incidence of drug resistance, reduced tendency for drug-induced secondary tumors, higher efficacy compared to other topoisomerase II inhibitors, in addition to good physicochemical and pharmacokinetic profiles.

Figure 1. Multifaceted implications of fluoroquinolones
(Source: Jukic A, et al. 2021)

Anti-FQs monoclonal antibody