DEVELOPMENT OF A THEORETICAL MODEL FOR ACTIVITY PREDICTION OF SECONDARY METABOLITES FROM THE ASTERACEAE FAMILY AS COX/LOX INHIBITORS.

Abstract

The discovery of substances that simultaneously act on the inhibition of the lipoxygenase (LOX) and cyclooxygenase (COX) pathway has been shown to be a promising strategy for obtaining new drugs. A multidisciplinary project to evaluate the inhibition of COX-1 and 5-LOX pathways employing metabolomics studies, in silico methods and in vitro enzymatic assays is already being developed by the research group AsterBioChem. To improve this research, molecular modeling techniques will be used to study and characterize the Asteraceae family metabolites, thus creating an in-house database. The molecular modeling suite MOE (Molecular Operating Environment), will be used to derive a pharmacophoric pattern from COX-1 and 5-LOX published inhibitors. The binding modes for protein-ligand docking and biological properties will be calculated using MOE, QikProp, PASS and DEREK softwares. These models will be validated by experimental data results and literature reports, thus developing a theoretical model that includes common features to both proteins. Using the BLAST software, homologous proteins to the desired target will be analyzed in order to select those inhibitors that are selective only to the COX/LOX pattern which will be tested (in vitro assays). In addition, it optimizes the discovery of active substances, and as a result, this approach still provides a reduction of costs, such as in organic solvents, reagents and drugs, which are used for isolation, purification and bioassays. It is, therefore, the full integration of in vivo, in vitro and in silico methods under the Modern Pharmacognosy.