Chemistry Research Laboratory, University of Oxford, 12 Mansfield Road, Oxford, OX1 3TA, UK.
Department of Chemistry, RCSI, 123 St. Stephens Green, Dublin 2, Ireland; SSPC, Synthesis and Solid State Pharmaceutical Centre, Ireland.
Curr Opin Chem Biol. 2020 Apr;55:59-68. doi: 10.1016/j.cbpa.2019.12.001. Epub 2020 Jan 13.
Click chemistry is fundamentally important to medicinal chemistry and chemical biology. It represents a powerful and versatile tool, which can be exploited to develop novel Pt-based anticancer drugs and to better understand the biological effects of Pt-based anticancer drugs at a cellular level. Innovative azide-alkyne cycloaddition-based approaches are being used to functionalise Pt-based complexes with biomolecules to enhance tumour targeting. Valuable information in relation to the mechanisms of action and resistance of Pt-based drugs is also being revealed through click-based detection, isolation and tracking of Pt drug surrogates in biological and cellular environments. Although less well-explored, inorganic Pt-click reactions enable synthesis of novel (potentially multimetallic) Pt complexes and provide plausible routes to introduce functional groups and monitoring Pt-azido drug localisation.
点击化学对药物化学和化学生物学至关重要。它代表了一种强大而多功能的工具,可以开发新型基于铂的抗癌药物,并更好地了解基于铂的抗癌药物在细胞水平上的生物学效应。创新的基于叠氮化物-炔烃环加成的方法被用于将生物分子功能化到基于铂的配合物上,以增强肿瘤靶向性。通过点击检测、分离和跟踪生物和细胞环境中的铂药物类似物,也揭示了与铂类药物的作用机制和耐药性相关的有价值的信息。尽管研究较少,但无机 Pt 点击反应能够合成新型(可能为多金属)Pt 配合物,并为引入功能基团和监测 Pt-叠氮药物定位提供了合理的途径。