Molecular Modeling Laboratory, Chemistry Department, Federal University of Lavras, 37200-000 Lavras, Brazil.
Biochemistry Laboratory, Chemistry Department, Federal University of Lavras, 37200-000 Lavras, Brazil.
Curr Med Chem. 2020;27(3):477-497. doi: 10.2174/0929867326666190201120646.
The inflammatory process is a natural self-defense response of the organism to damage agents and its action mechanism involves a series of complex reactions. However, in some cases, this process can become chronic, causing much harm to the body. Therefore, over the years, many anti-inflammatory drugs have been developed aiming to decrease the concentrations of inflammatory mediators in the organism, which is a way of controlling these abnormal chain reactions. The main target of conventional anti-inflammatory drugs is the cyclooxygenase (COX) enzyme, but its use implies several side effects. Thus, based on these limitations, many studies have been performed, aiming to create new drugs, with new action mechanisms. In this sense, the phospholipase A2 (PLA2) enzymes stand out. Among all the existing isoforms, secretory PLA2 is the major target for inhibitor development, since many studies have proven that this enzyme participates in various inflammatory conditions, such as cancer, Alzheimer and arthritis. Finally, for the purpose of developing anti-inflammatory drugs that are sPLA2 inhibitors, many molecules have been designed. Accordingly, this work presents an overview of inflammatory processes and mediators, the current available anti-inflammatory drugs, and it briefly covers the PLA2 enzymes, as well as the diverse structural array of the newest sPLA2 inhibitors as a possible target for the production of new anti-inflammatory drugs.
炎症过程是机体对损伤因子的天然自卫反应，其作用机制涉及一系列复杂反应。然而，在某些情况下，这个过程可能会变成慢性的，对身体造成很大的伤害。因此，多年来，已经开发出许多抗炎药物，旨在降低机体中炎症介质的浓度，从而控制这些异常的连锁反应。传统抗炎药物的主要靶标是环氧化酶（COX）酶，但它的使用会带来一些副作用。因此，基于这些局限性，已经进行了许多研究，旨在创造具有新作用机制的新药。在这方面，磷脂酶 A2（PLA2）酶尤为突出。在所有现有的同工酶中，分泌型 PLA2 是抑制剂开发的主要靶标，因为许多研究已经证明该酶参与了各种炎症情况，如癌症、阿尔茨海默病和关节炎。最后，为了开发抑制 sPLA2 的抗炎药物，已经设计了许多分子。因此，这项工作概述了炎症过程和介质、现有的抗炎药物，并简要介绍了 PLA2 酶，以及最新的 sPLA2 抑制剂的多样化结构，作为产生新抗炎药物的可能靶标。
