Department of Pharmaceutical Sciences, University of Perugia, Via del Liceo, 06123 Perugia, Italy.
Molecules. 2021 Nov 19;26(22):6996. doi: 10.3390/molecules26226996.
Antimicrobial resistance (AMR) is a complex threat to human health and, to date, it represents a hot topic in drug discovery. The use of non-antibiotic molecules to block resistance mechanisms is a powerful alternative to the identification of new antibiotics. Bacterial efflux pumps exert the early step of AMR development, allowing the bacteria to grow in presence of sub-inhibitory drug concentration and develop more specific resistance mechanisms. Thus, efflux pump inhibitors (EPIs) offer a great opportunity to fight AMR, potentially restoring antibiotic activity. Based on our experience in designing and synthesizing novel EPIs, herein, we retrieved information around quinoline and indole derivatives reported in literature on this topic. Thus, our aim was to collect all data around these promising classes of EPIs in order to delineate a comprehensive structure-activity relationship (SAR) around each core for different microbes. With this review article, we aim to help future research in the field in the discovery of new microbial EPIs with improved activity and a better safety profile.
抗微生物药物耐药性 (AMR) 是对人类健康的一个复杂威胁，迄今为止，它是药物发现中的一个热门话题。使用非抗生素分子来阻断耐药机制是识别新抗生素的一种强有力的替代方法。细菌外排泵发挥了 AMR 发展的早期步骤，使细菌能够在亚抑制药物浓度下生长，并发展出更具特异性的耐药机制。因此，外排泵抑制剂 (EPI) 为对抗 AMR 提供了一个很好的机会，有可能恢复抗生素的活性。基于我们在设计和合成新型 EPI 方面的经验，本文检索了文献中报道的有关喹啉和吲哚衍生物的信息。因此，我们的目的是收集有关这些有前途的 EPI 类别的所有数据，以便为不同微生物的每个核心勾勒出全面的结构-活性关系 (SAR)。通过这篇综述文章，我们旨在帮助该领域未来的研究发现具有更好活性和更好安全性的新型微生物 EPI。
