Department of Pharmacognosy, Bioanalysis and Drug Discovery, Faculty of Pharmacy, Universite Libre de Bruxelles (ULB), Boulevard du Triomphe, 1050 Bruxelles, Belgium.
Microbiology, Bioorganic and Macromolecular Chemistry, Faculty of Pharmacy, Universite Libre de Bruxelles, Campus de la Plaine, Boulevard du Triomphe, 1050 Bruxelles, Belgium.
Curr Med Chem. 2018;25(21):2418-2447. doi: 10.2174/0929867325666180117103919.
Group IV cytosolic phospholipase A2 (cPLA2α) plays a critical role in inflammatory processes. It produces arachidonic acid which is the main source of the pro-inflammatory eicosanoids mediators that are important in innate immune system. In some cases, these proinflammatory mediators cause damages to the host tissues and therefore promote autoimmune diseases. Consequently, development of potent inhibitors against cPLA2α could improve the therapy of inflammatory diseases. In the last two decades, intense efforts have been done to find potent cPLA2α inhibitors. Several scaffolds have been developed with the use of structure activity relationship (SAR) studies, and potent inhibitors have been obtained. The poor absorption of these compounds from intestine was the main challenge for clinical application. This review illustrates the search for cPLA2α inhibitors, their SAR studies and biological effects.
细胞溶质 IV 型磷脂酶 A2（cPLA2α）在炎症过程中起着关键作用。它产生花生四烯酸，是炎症性类二十烷酸介质的主要来源，这些介质在先天免疫系统中很重要。在某些情况下，这些促炎介质会对宿主组织造成损害，从而促进自身免疫性疾病。因此，开发针对 cPLA2α 的有效抑制剂可以改善炎症性疾病的治疗。在过去的二十年中，人们进行了大量的努力来寻找有效的 cPLA2α 抑制剂。已经使用结构活性关系（SAR）研究开发了几种支架，并获得了有效的抑制剂。这些化合物从肠道吸收不良是临床应用的主要挑战。本综述说明了寻找 cPLA2α 抑制剂、它们的 SAR 研究和生物学效应的过程。
