Fluoroquinolones as versatile scaffolds: Potential for targeting classical and novel mechanisms to combat antibacterial resistance

IF 4.7 3区 医学 Q1 PHARMACOLOGY & PHARMACY
Ahmed M. Kamal El-sagheir , Michaela Wenzel , Jari Yli-Kauhaluoma
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引用次数: 0

Abstract

Antibiotics play an essential role in combating infectious diseases. Due to the emergence of multidrug-resistant bacteria, the efficacy of antibiotic therapy is continually decreasing. Consequently, there is an urgent need for the development of novel antibiotics, preferably with novel targets that have not yet been clinically exploited and/or multiple mechanisms of action, reducing the probability of fast resistance development. Recently, several new promising antibacterial targets have been identified, including N-acetylglucosamine-6-phosphate deacetylase, glucosamine-6-phosphate synthase, metal-dependent deacetylase, and carbonic anhydrase. Additionally, inhibition of biofilm formation enhances bacterial susceptibility to antibiotics and potentially minimizes the risk of resistance development. This review discusses fluoroquinolones as versatile scaffolds, covering their structure-activity relationships, recent modifications and their role in inhibiting multiple bacterial targets. Multi-target fluoroquinolone derivatives exhibit enhanced activity against multidrug-resistant bacteria, including Gram-positive, Gram-negative, and mycobacterial species. Therefore, the continued optimization of fluoroquinolone structures represents an attractive approach to combat antibacterial resistance and achieve better therapeutic outcomes.

Abstract Image

氟喹诺酮类药物作为多功能支架:靶向对抗抗菌耐药的经典和新型机制的潜力。
抗生素在防治传染病方面发挥着重要作用。由于耐多药细菌的出现,抗生素治疗的效果不断下降。因此,迫切需要开发新型抗生素,最好是具有尚未临床开发的新靶点和/或多种作用机制,以减少快速耐药发展的可能性。近年来,人们发现了几种新的抑菌靶点,包括n -乙酰氨基-6-磷酸脱乙酰酶、氨基-6-磷酸合酶、金属依赖性脱乙酰酶和碳酸酐酶。此外,抑制生物膜的形成增强了细菌对抗生素的敏感性,并潜在地将耐药性发展的风险降至最低。本文综述了氟喹诺酮类药物作为多功能支架,包括它们的结构-活性关系,最近的修饰及其在抑制多种细菌靶点中的作用。多靶点氟喹诺酮衍生物对多重耐药细菌(包括革兰氏阳性、革兰氏阴性和分枝杆菌)的活性增强。因此,氟喹诺酮类药物结构的持续优化是对抗抗菌耐药和获得更好治疗效果的一种有吸引力的方法。
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来源期刊
CiteScore
9.60
自引率
2.20%
发文量
248
审稿时长
50 days
期刊介绍: The journal publishes research articles, review articles and scientific commentaries on all aspects of the pharmaceutical sciences with emphasis on conceptual novelty and scientific quality. The Editors welcome articles in this multidisciplinary field, with a focus on topics relevant for drug discovery and development. More specifically, the Journal publishes reports on medicinal chemistry, pharmacology, drug absorption and metabolism, pharmacokinetics and pharmacodynamics, pharmaceutical and biomedical analysis, drug delivery (including gene delivery), drug targeting, pharmaceutical technology, pharmaceutical biotechnology and clinical drug evaluation. The journal will typically not give priority to manuscripts focusing primarily on organic synthesis, natural products, adaptation of analytical approaches, or discussions pertaining to drug policy making. Scientific commentaries and review articles are generally by invitation only or by consent of the Editors. Proceedings of scientific meetings may be published as special issues or supplements to the Journal.
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