Rusu Aura, Lungu Ioana-Andreea, Moldovan Octavia-Laura, Tanase Corneliu, Hancu Gabriel
Pharmaceutical and Therapeutical Chemistry Department, Faculty of Pharmacy, George Emil Palade University of Medicine, Pharmacy, Science, and Technology of Targu Mures, 540142 Targu Mures, Romania.
The Doctoral School of Medicine and Pharmacy, George Emil Palade University of Medicine, Pharmacy, Science, and Technology of Targu Mures, 540142 Targu Mures, Romania.
Pharmaceutics. 2021 Aug 18;13(8):1289. doi: 10.3390/pharmaceutics13081289.
The evolution of the class of antibacterial quinolones includes the introduction in therapy of highly successful compounds. Although many representatives were withdrawn due to severe adverse reactions, a few representatives have proven their therapeutical value over time. The classification of antibacterial quinolones into generations is a valuable tool for physicians, pharmacists, and researchers. In addition, the transition from one generation to another has brought new representatives with improved properties. In the last two decades, several representatives of antibacterial quinolones received approval for therapy. This review sets out to chronologically outline the group of approved antibacterial quinolones since 2000. Special attention is given to eight representatives: besifloxacin, delafoxacin, finafloxacin, lascufloxacin, nadifloxacin and levonadifloxacin, nemonoxacin, and zabofloxacin. These compounds have been characterized regarding physicochemical properties, formulations, antibacterial activity spectrum and advantageous structural characteristics related to antibacterial efficiency. At present these new compounds (with the exception of nadifloxacin) are reported differently, most often in the fourth generation and less frequently in a new generation (the fifth). Although these new compounds' mechanism does not contain essential new elements, the question of shaping a new generation (the fifth) arises, based on higher potency and broad spectrum of activity, including resistant bacterial strains. The functional groups that ensured the biological activity, good pharmacokinetic properties and a safety profile were highlighted. In addition, these new representatives have a low risk of determining bacterial resistance. Several positive aspects are added to the fourth fluoroquinolones generation, characteristics that can be the basis of the fifth generation. Antibacterial quinolones class continues to acquire new compounds with antibacterial potential, among other effects. Numerous derivatives, hybrids or conjugates are currently in various stages of research.
抗菌喹诺酮类药物的发展历程包括引入了一些极为成功的治疗用化合物。尽管许多代表药物因严重不良反应而退市，但随着时间推移，仍有少数代表药物证明了其治疗价值。将抗菌喹诺酮类药物划分为不同代次，这对医生、药剂师和研究人员而言是一项很有价值的工具。此外，从一代到另一代的转变带来了性能更优的新代表药物。在过去二十年中，几种抗菌喹诺酮类药物代表获得了治疗应用的批准。本综述旨在按时间顺序概述自2000年以来获批的抗菌喹诺酮类药物。特别关注了八种代表药物：贝西沙星、德拉沙星、非那沙星、拉斯库沙星、那氟沙星和左氧那氟沙星、奈诺沙星以及扎氟沙星。已对这些化合物的物理化学性质、剂型、抗菌活性谱以及与抗菌效力相关的有利结构特征进行了表征。目前，这些新化合物（那氟沙星除外）的报道方式各不相同，大多被归为第四代，较少被归为新一代（第五代）。尽管这些新化合物的作用机制并未包含本质上新的元素，但基于更高的效力和更广的活性谱，包括对耐药菌株的活性，出现了划分新一代（第五代）的问题。突出了确保生物活性、良好药代动力学性质和安全性的官能团。此外，这些新代表药物产生细菌耐药性的风险较低。第四代氟喹诺酮类药物增添了几个积极方面的特性，这些特性可作为第五代的基础。抗菌喹诺酮类药物类别继续获得具有抗菌潜力等其他作用的新化合物。目前，众多衍生物、杂化物或缀合物正处于不同的研究阶段。
