Centre for Synthesis and Chemical Biology, UCD School of Chemistry, University College Dublin, Belfield, D04 N2E5 Dublin, Ireland.
Molecules. 2024 May 10;29(10):2233. doi: 10.3390/molecules29102233.
This review article assembles key recent advances in the synthetic chemistry and biology of specialised pro-resolving mediators (SPMs). The major medicinal chemistry developments in the design, synthesis and biological evaluation of synthetic SPM analogues of lipoxins and resolvins have been discussed. These include variations in the top and bottom chains, as well as changes to the triene core, of lipoxins, all changes intended to enhance the metabolic stability whilst retaining or improving biological activity. Similar chemical modifications of resolvins are also discussed. The biological evaluation of these synthetic SPMs is also described in some detail. Original investigations into the biological activity of endogenous SPMs led to the pairing of these ligands with the FPR2/LX receptor, and these results have been challenged in more recent work, leading to conflicting results and views, which are again discussed.
这篇综述文章汇集了专门促炎消退介质（SPM）的合成化学和生物学方面的最新重要进展。讨论了脂氧素和 resolvin 的合成 SPM 类似物的设计、合成和生物评价方面的主要药物化学进展。这些进展包括脂氧素的顶链和底链的变化，以及三烯核心的变化，所有这些变化旨在提高代谢稳定性，同时保持或提高生物活性。还讨论了 resolvin 的类似化学修饰。还详细描述了这些合成 SPM 的生物学评估。对内源性 SPM 生物活性的原始研究导致这些配体与 FPR2/LX 受体配对，而这些结果在最近的工作中受到挑战，导致相互矛盾的结果和观点，这再次进行了讨论。
