Evaluation of the influence of fluoroquinolone chemical structure on stability: forced degradation and in silico studies

Abstract

Fluoroquinolones are a known antibacterial class commonly used around the world. These compounds present relative stability and they may show some adverse effects according their distinct chemical structures. The chemical hydrolysis of five fluoroquinolones was studied using alkaline and photolytic degradation aiming to observe the differences in molecular reactivity. DFT/B3LYP-6.31G* was used to assist with understanding the chemical structure degradation. Gemifloxacin underwent degradation in alkaline medium. Gemifloxacin and danofloxacin showed more degradation perceptual indices in comparison with ciprofloxacin, enrofloxacin and norfloxacin in photolytic conditions. Some structural features were observed which may influence degradation, such as the presence of five member rings attached to the quinolone ring and the electrostatic positive charges, showed in maps of potential electrostatic charges. These measurements may be used in the design of effective and more stable fluoroquinolones as well as the investigation of degradation products from stress stability assays.

Co‐occurrence characteristics of antibiotics and estrogens and their relationships in a lake system affected by wastewater

“…Levofloxacin was predominant in the treated wastewater and in the three rivers. Fluoroquinolones tend to be more stable and quickly accumulate in water–sediment systems, such as lakes and rivers (Bairros et al., 2018). They are hard to degrade and are easily transported, leading to a large amount in aquatic ecosystems (Rusch, Spielmeyer, Zorn, & Hamscher, 2019).…”

Biological Effects of Quinolones: A Family of Broad-Spectrum Antimicrobial Agents

“…For enrofloxacin, an FQ used only in veterinary medicine, a study of excretion kinetics found that after oral administration 74% was excreted unchanged and 25% was metabolized to ciprofloxacin, the FQ most used in humans [ 308 ]. Among the factors that affect the stability of FQs, forced degradation studies and simulated solar irradiation studies have shown that photolytic conditions can promote FQs degradation, this being the main degradation pathway on aquatic surfaces [ 300 , 309 , 310 ]. Alkalinity conditions have also been reported to promote the degradation of FQs [ 309 ].…”

“…Among the factors that affect the stability of FQs, forced degradation studies and simulated solar irradiation studies have shown that photolytic conditions can promote FQs degradation, this being the main degradation pathway on aquatic surfaces [ 300 , 309 , 310 ]. Alkalinity conditions have also been reported to promote the degradation of FQs [ 309 ].…”

Impact of ciprofloxacin impurities on bacterial growth, antibiotic resistance development and content assays

“…1ai) (Husain et al 1995). Intermediates, including FQA (7-Chloro-1-cyclopropyl-6fluoro-1,4-dihydro-4-oxoquinoline-3-carboxylic acid), are formed during the process and remain present in small amounts Fluoroquinolone antibiotics display susceptibility to UV degradation and photolytic cleavage (Adam et al 2012;Bushra et al 2013;Singh and Gupta 2014;de Bairros et al 2018). Production of CEA -amino]-3quinolinecarboxylic acid hydrochloride) (Fig.…”

“…2013; Singh and Gupta 2014; de Bairros et al . 2018). Production of CEA (1‐Cyclopropyl‐6‐fluoro‐1, 4‐dihydro‐4‐oxo‐7‐[(2‐aminoethyl)‐amino]‐3‐quinolinecarboxylic acid hydrochloride) (Fig.…”