Magaña Angel J, Sklenicka Jan, Pinilla Clemencia, Giulianotti Marc, Chapagain Prem, Santos Radleigh, Ramirez Maria Soledad, Tolmasky Marcelo E
Center for Applied Biotechnology Studies, Department of Biological Science, College of Natural Sciences and Mathematics, California State University Fullerton Fullerton CA 92831 USA
Center for Translational Science, Florida International University Port St. Lucie FL 34987 USA.
RSC Med Chem. 2023 Jul 21;14(9):1591-1602. doi: 10.1039/d3md00226h. eCollection 2023 Sep 19.
Growing resistance to antimicrobial medicines is a critical health problem that must be urgently addressed. Adding to the increasing number of patients that succumb to infections, there are other consequences to the rise in resistance like the compromise of several medical procedures and dental work that are heavily dependent on infection prevention. Since their introduction in the clinics, aminoglycoside antibiotics have been a critical component of the armamentarium to treat infections. Still, the increase in resistance and their side effects led to a decline in their utilization. However, numerous current factors, like the urgent need for antimicrobials and their favorable properties, led to renewed interest in these drugs. While efforts to design new classes of aminoglycosides refractory to resistance mechanisms and with fewer toxic effects are starting to yield new promising molecules, extending the useful life of those already in use is essential. For this, numerous research projects are underway to counter resistance from different angles, like inhibition of expression or activity of resistance components. This review focuses on selected examples of one aspect of this quest, the design or identification of small molecule inhibitors of resistance caused by enzymatic modification of the aminoglycoside. These compounds could be developed as aminoglycoside adjuvants to overcome resistant infections.
对抗菌药物的耐药性不断增加是一个必须紧急解决的关键健康问题。除了越来越多的患者死于感染外，耐药性增加还带来了其他后果，比如一些严重依赖感染预防的医疗程序和牙科手术受到影响。自引入临床以来，氨基糖苷类抗生素一直是治疗感染的重要药物组成部分。然而，耐药性的增加及其副作用导致其使用量下降。不过，当前的诸多因素，如对抗菌药物的迫切需求及其良好特性，使得人们对这些药物重新产生了兴趣。虽然设计对耐药机制具有抗性且毒性较小的新型氨基糖苷类药物的努力已开始产生新的有前景的分子，但延长现有药物的使用寿命至关重要。为此，许多研究项目正在从不同角度对抗耐药性，如抑制耐药成分的表达或活性。本综述重点关注这一探索的一个方面的选定实例，即由氨基糖苷酶促修饰引起的耐药性小分子抑制剂的设计或鉴定。这些化合物可开发为氨基糖苷类佐剂，以克服耐药性感染。
