Yusuf Hamied Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge, CB2 1EW, UK.
Biol Chem. 2021 Jul 13;403(4):363-375. doi: 10.1515/hsz-2021-0253. Print 2022 Mar 28.
The occurrence of drug-resistant bacteria is drastically rising and new and effective antibiotic classes are urgently needed. However, most of the compounds in development are minor modifications of previously used drugs to which bacteria can easily develop resistance. The investigation of inorganic and organometallic compounds as antibiotics is an alternative approach that holds great promises due to the ability of such molecules to trigger metal-specific mechanisms of action, which results in lethal consequences for pathogens. In this review, a selection of concepts to rationally design inorganic and organometallic antibiotics is discussed, highlighting their advantages by comparing them to classical drug discovery programmes. The review concludes with a short perspective for the future of antibiotic drug development and the role metal-based compounds will play in the field.
耐药菌的出现急剧上升，急需新的、有效的抗生素类别。然而，大多数正在开发的化合物都是以前使用的药物的微小修饰，细菌很容易对这些药物产生耐药性。将无机和金属有机化合物作为抗生素进行研究是一种替代方法，由于这些分子能够触发针对金属的特定作用机制，从而对病原体产生致命后果，因此具有很大的发展前景。在这篇综述中，讨论了合理设计无机和金属有机抗生素的一些概念，通过与经典药物发现方案进行比较，突出了它们的优势。最后，对未来抗生素药物开发的前景以及金属基化合物在该领域将发挥的作用进行了展望。
