Estudo da relação estrutura-atividade de flavonoides sintéticos com potencial atividade inibitória da fosfolipase A2

Abstract

The flavonoids are organics compounds eidely distributed in nature and have been the target of many searches. Studies point the flavonoids use as phospholipase A enzyme from class 2 (PLA2), make them compounds with antiinflamatory potencial, since this enzyme act in arachidonic acid liberation. Due they make part of the feeding, that introduce the idea they aren't toxics, make them interesting, because the medicines usually use to this aim present some kind of collateral effect, however its necessary the action mechanism knowledge by these bioactives substances, so that the flavonoids have been used as possible drugs. So, were maked tests in vivo as edematous and myotoxic activities, both assist in compounds act in enzyme PLA2 inhibition. Therefore, were maked chemistry quantum calculation that assist in obtain structural and eletronic informations. These are obtained through the Density Functional Theory (DFT), by hybrid functional B3LYP, the method was verified with the whole basis set 6-31G*, 6-31++G**, and cc-pVTZ. To compare teorics with experimental results, use statistic and mathmatic methodology called chemometric. Among the various chemometrics methods, used the hierarchical groups of analysis (HCA) and the principals compounds analysis (PCA). The synthetics flavones analysis shows that they present inhibitory activity to tha PLA2, this can be justified because the OH presence in 7 that can be interact by hydrogen bond with the enzyme active site. Besides, the chemometrics showwed descriptors like dipole moment, log p, polarizability, HOMO and drowsiness can take to one theoric model give us a good inhibitory activity PLA2 forecast, by flavones, helping in inhibitors drugs drawing of this enzyme and, the environment (vacuo and DMSO), exert significant ingluence on its inhibitory activity. Therefore, the flavones present results very promising for the PLA2 inhibition, where the most active are that present the big lateral structure, 3' and 4'-octoxiflavones. Although obtained results been satisfactory, we suggest analoga substances drawing have been maked, thereby we can have a whole chemometrics analysis, and molecular modeling to value the flavones fit in the target site and check i the inhibition is in fact on the enzyme active site.