Metabolomics, enzymatic targets and in silico tools in the search of bioactive compounds from plants

Abstract

With the fast development of analytical techniques, especially chromatography and spectrometry, the time required for separation, isolation and identification of compounds from natural origin has decreased. Thus, the discovery process of novel biologically active compounds from natural resources has been facilitated, even more when this process is associated with in silico methods, for example within the scope of metabolomics. With the aim to increase productivity in the search for new or bioactive compounds as well as to carry out in silico studies (virtual screening) and dereplication of biological matrices, it is also important to create collections of pure compound and their respective chemical structures, collections of extracts and chromatographic fractions. Therefore, the main aim of this project is to carry out a metabolomic approach based on liquid chromatography coupled to mass spectrometry as well as in silico methods to find natural compounds from plants from the family Asteraceae with anti-inflammatory and antiparasitic potential. The selected targets are enzymes related to inflammation (cyclooxygenase and lipoxygenase) and to diseases caused by protozoan parasites (dihydroorotate dehydrogenase - DHODH from Trypanosoma cruzi and Leishmania major). Besides, it is also proposed to develop a pure compound library, an extract library, a chemical structures library and an integrated database. Chemical structures from extract dereplication and those from the bibliographic survey of the plant groups involved in this study as well as bioactivity data will be used to carry out virtual screening of compounds with anti-inflammatory potential. The data from this project will be integrated and merged into a database. Thus, this proposal deals with the development of an integrated platform for the discovery of bioactive compounds and dereplication. (AU)