Physical Chemistry and Applied Spectroscopy, Chemistry Division, Los Alamos National Laboratory, Los Alamos, NM 87545, USA.
Toxins (Basel). 2021 May 12;13(5):347. doi: 10.3390/toxins13050347.
Macrolides are a diverse class of hydrophobic compounds characterized by a macrocyclic lactone ring and distinguished by variable side chains/groups. Some of the most well characterized macrolides are toxins produced by marine bacteria, sea sponges, and other species. Many marine macrolide toxins act as biomimetic molecules to natural actin-binding proteins, affecting actin polymerization, while other toxins act on different cytoskeletal components. The disruption of natural cytoskeletal processes affects cell motility and cytokinesis, and can result in cellular death. While many macrolides are toxic in nature, others have been shown to display therapeutic properties. Indeed, some of the most well known antibiotic compounds, including erythromycin, are macrolides. In addition to antibiotic properties, macrolides have been shown to display antiviral, antiparasitic, antifungal, and immunosuppressive actions. Here, we review each functional class of macrolides for their common structures, mechanisms of action, pharmacology, and human cellular targets.
大环内酯类是一类具有疏水性的化合物,其特征为大环内酯环和可变的侧链/基团。一些最具特征的大环内酯类是由海洋细菌、海海绵和其他物种产生的毒素。许多海洋大环内酯类毒素作为天然肌动蛋白结合蛋白的仿生分子起作用,影响肌动蛋白聚合,而其他毒素则作用于不同的细胞骨架成分。天然细胞骨架过程的破坏会影响细胞运动和胞质分裂,并可能导致细胞死亡。虽然许多大环内酯类化合物在本质上是有毒的,但也有一些已被证明具有治疗特性。事实上,一些最著名的抗生素化合物,包括红霉素,都是大环内酯类。除了抗生素特性外,大环内酯类还显示出抗病毒、抗寄生虫、抗真菌和免疫抑制作用。在这里,我们将根据其常见结构、作用机制、药理学和人类细胞靶标,对每种功能类别大环内酯类进行综述。