Síntese, caracterização e avaliação biológica de ciclonucleosídeos, bioisósteros do resveratrol e heterociclos nitrogenados

Abstract

This work deals with the research for discovery of potential drugs against neglected diseases and has been divided into three parts. The first part presents a new methodology for synthesis of cyclo-nucleosides from carbohydrate (D-glucose and D-xylose) analogues specifically N3, 2'-cyclo-nucleosides until then unpublished in literature. This methodology was applied to obtain an analogue of 5'-methyl-tioadenosina (MTA), an important metabolite regulator, controller of 5'-methyl-tioadenosine/Sadenosylhomocysteine (MTA / SAH) nucleosidase. The second part of this work concerns the synthesis of resveratrol bioisosters, a major metabolite found in higher plants. Since the discovery of its cardioprotective and antioxidants effects and several research associates this compound for new potential medicines. Thus, using the tool of classical isosteric, where C=C bond between the rings is replaced by a C=N bond, summed up a series of analogues of resveratrol. The third and final issues addressed in this work were the preparation and biological evaluation of heterocyclic compounds containing nitrogen as heteroatom. We carried out the synthesis of three distinct series of nitrogen heterocycles, specifically imidazolidines, hexahydropyrimidines and benzimidazole were obtained through rapid and efficient syntheses. The compounds were characterized by different spectroscopic techniques, namely infrared, 1D and 2D NMR, high resolution mass spectrometry and elemental analysis and were bioassayed in order to test their potential as antileishmanial, antibacterial, antitubercular, antioxidant, antimalarial and anti-Chagas agents.