Phospholipases A2 (PLA2) as target enzymes for new anti-inflammatory drugs: a theoretical and experimental study

Abstract

Having in mind the complex process of drug design, techniques that can help in research and provide data that facilitate this process be of great value. In this context, many computational resources have been stands out. By mean of them, it is possible to obtain data about mechanism of action of these drugs, new suggestions of improved structures for synthesis, selectivity, clarify about the side effects, etc. In addition, using the computational chemistry becomes easier to find the best molecules, or inhibitors, which are capable of exert its activity of a more efficient way, with less dose. This helps to develop increasingly specific compounds, aiming to improve many problems related to the side effects of the drugs. A class of drugs that is widely used throughout the world population, but which has several side effects, such as gastrotoxicity, hepatotoxicity and cardiovascular diseases are Nonsteroidal Anti-inflammatory (NSAIDs), which includes the class of selective COXIBs inhibitors. Thus, the development of drugs with anti-inflammatory activity, but that act of different form of the existing inhibitors, aiming to minimize the damage to the organism, are of great importance. In this context, the use of secreted phospholipase A2 inhibitors as potential anti-inflammatory drugs has been highlighted. Phospholipases A2 are the enzymes that initiate the cascade of arachidonic acid, which gives rise to inflammatory mediators. The objective of this work was to present, in a summarized way, the steps of the inflammatory process and the role of the phospholipase A2 enzymes, as well as to bring some existing inhibitors and their potential. In addition, theoretical calculations and experimental results were also carried out to evaluate the potential of snake venom phospholipases A2 to replace human enzymes in experimental trials. The theoretical data found together with the experimental data corroborate that the BthTX-II snake venom enzyme can be used as an experimental model for human HGIIA phospholipase A2, which may greatly aid in the development of anti-inflammatory drugs, since enzymes are more easily obtained.