Fluoroquinolones Hybrid Molecules as Promising Antibacterial Agents in the Fight against Antibacterial Resistance

Abstract

The emergence of bacterial resistance has motivated researchers to discover new antibacterial agents. Nowadays, fluoroquinolones keep their status as one of the essential classes of antibacterial agents. The new generations of fluoroquinolones are valuable therapeutic tools with a spectrum of activity, including Gram-positive, Gram-negative, and atypical bacteria. This review article surveys the design of fluoroquinolone hybrids with other antibacterial agents or active compounds and underlines the new hybrids’ antibacterial properties. Antibiotic fluoroquinolone hybrids have several advantages over combined antibiotic therapy. Thus, some challenges related to joining two different molecules are under study. Structurally, the obtained hybrids may contain a cleavable or non-cleavable linker, an essential element for their pharmacokinetic properties and mechanism of action. The design of hybrids seems to provide promising antibacterial agents helpful in the fight against more virulent and resistant strains. These hybrid structures have proven superior antibacterial activity and less susceptibility to bacterial resistance than the component molecules. In addition, fluoroquinolone hybrids have demonstrated other biological effects such as anti-HIV, antifungal, antiplasmodic/antimalarial, and antitumor activity. Many fluoroquinolone hybrids are in various phases of clinical trials, raising hopes that new antibacterial agents will be approved shortly.

Pseudomonas aeruginosa: Infections, Animal Modeling, and Therapeutics

“…Fluoroquinolones are also recommended for the first line of treatment in acute otitis externa or skin and soft tissue infections and complicated UTI caused by P. aeruginosa strains that are found to be susceptible to these agents [223,224,[257][258][259][260]. Limitations with the use of fluoroquinolones include rapid development of resistance in bacteria [261] and the sensitivity of fluoroquinolones to acidic conditions, which adversely affect their cell uptake [262,263], although recently developed novel fluoroquinolones (i.e., delafloxacin) show improved cellular uptake and maintain their antibacterial activities in acidic conditions [263].…”

Overview of Side-Effects of Antibacterial Fluoroquinolones: New Drugs versus Old Drugs, a Step Forward in the Safety Profile?

“…The classification into generations based on the spectrum of activity and therapeutic indications is the most used. New compounds are acquired from one generation to another with a broader spectrum of activity ( Table 1 ) and improved pharmacokinetic properties [ 38 ]. Among the representatives of the fourth generation are topical FQs (ophthalmic and otic), such as besifloxacin [ 39 ] and finafloxacin [ 21 ].…”

“…Structural characterization of FQs (older and newer representatives) was recently described in two other papers by our group of authors [ 4 , 38 ]. Essential structural elements of FQs will be briefly highlighted below.…”

“…On 15 November 2018, the EMA completed an evaluation of significant, debilitating, and possibly irreversible AEs associated with QNs and FQs antibiotics administered orally, injectable, or inhaled, considering the experiences of patients, healthcare workers, and scientists. Following this evaluation, the EMA’s Pharmacovigilance Risk Assessment Committee (PRAC) has suggested that some medications, particularly those containing QNs, should be withdrawn from the market [ 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 , 62 , 63 , 64 , 65 , 66 , 67 , 68 , 69 , 70 ]. The QNs and FQs subject to these restrictions are: (a) cinoxacin, nalidixic acid, pipemidic acid (QNs), and (b) ciprofloxacin, flumequine, levofloxacin, lomefloxacin, moxifloxacin, norfloxacin, ofloxacin, pefloxacin, prulifloxacin, and rufloxacin (FQs) [ 34 ].…”

Ag/Ag2O with NIR-Triggered Antibacterial Activities: Photocatalytic Sterilization Enhanced by Low-Temperature Photothermal Effect

“…1,2 However, resulting from the longterm misuse and overuse of antibiotics, the emergence of antibiotic-resistant bacteria has become an even trickier issue, which therefore evoked the need for effective antibacterial therapeutic strategies without the side effects of causing bacterial resistance. [3][4][5][6] Recent studies aiming to tackle these problems have attached much attention to developing photoresponsive materials due to their robust and rapid bactericidal activities. [7][8][9] In phototherapeutic approaches, photoresponsive materials, in the first place, respond to light at appropriate wavelengths, ranging from ultraviolet (UV) to NIR, which is then followed by the production of reactive oxygen species (ROS) and hyperthermia.…”