Université Grenoble Alpes, CNRS 5063, DPM, 38000 Grenoble, France.
Université Grenoble Alpes, CNRS 5250, DCM, 38000 Grenoble, France.
J Med Chem. 2022 Oct 13;65(19):12594-12625. doi: 10.1021/acs.jmedchem.2c01150. Epub 2022 Sep 20.
Hemiindigoids comprise a range of natural and synthetic scaffolds that share the same aromatic hydrocarbon backbone as well as promising biological and optical properties. The encouraging therapeutic potential of these scaffolds has been unraveled by many studies over the past years and uncovered representants with inspiring pharmacophoric features such as the acetylcholinesterase inhibitor donezepil and the tubulin polymerization inhibitor indanocine. In this review, we summarize the last advances in the medicinal potential of hemiindigoids, with a special attention to molecular design, structure-activity relationship, ligand-target interactions, and mechanistic explanations covering their effects. As their strong fluorogenic potential and photoswitch behavior recently started to be highlighted and explored in biology, giving rise to the development of novel fluorescent probes and photopharmacological agents, we also discuss these properties in a medicinal chemistry perspective.
半吲哚类化合物包括一系列天然和合成的支架,它们具有相同的芳烃骨架,以及有前途的生物和光学性质。这些支架的令人鼓舞的治疗潜力已经被过去几年的许多研究揭示出来,并发现了具有令人鼓舞的药效特征的代表物,如乙酰胆碱酯酶抑制剂多奈哌齐和微管蛋白聚合抑制剂吲达辛。在这篇综述中,我们总结了半吲哚类化合物在医学潜力方面的最新进展,特别关注分子设计、构效关系、配体-靶标相互作用以及解释其作用的机制。由于它们强烈的荧光潜力和光开关行为最近开始在生物学中得到强调和探索,从而开发出新型荧光探针和光药理学试剂,我们也从药物化学的角度讨论了这些性质。