Síntese, caracterização e avaliação antiparasitária de novos 1,2,3-triazóis

Abstract

The present thesis, entitled "Synthesis, characterization and antiparasitic evaluation of new 1,2,3-triazoles", deals with the preparation, characterization and antileishmanial evaluation of organic compounds containing a 1,4-disubstituted triazolic ring, containing an alkyl chain in position 1 and different functional groups (epoxide, crotonoyl and esters) in position 4 and, also, their respective salts, the ionic liquids. In all, 37 triazole derivatives were obtained, 28 of which were unpublished. To obtain non-ionic triazole derivatives, “click chemistry” reactions, bimolecular substitution reactions, acetylation and also esterification were used. Ionic liquids were synthesized via N-alkylation reactions. The chemical structures of the products obtained were confirmed by mass spectrometry, 1H and 13C nuclear magnetic resonance and fusion range (when solid). The synthesized compounds were evaluated in promastigote and amastigote forms of Leishmania amazonensis, as well as the toxic effect on macrophages, considered as the main host cells of this parasite. The results showed that, in general, ionic liquids had a better antileishmanial effect and, despite the toxicity in macrophages, some were more effective on parasites than on host cells. Among all the synthesized triazole compounds, the TS-2c derivative was the one that presented the best activity results in in vitro tests, with IC50 values of 3.61 µM and 761 µM in the promastigote and amastigote forms, respectively. For this reason, it was chosen for the development of a brief in vivo experiment in Leishmania infantum, however the results for this species were not as promising as the in vitro results in Lesihamnia amazonensis. These studies confirm the antileishmanial activity of triazole derivatives, with a special emphasis on salts, and encourage further exploration of the biological effect of this class of molecules on Leishmania spp.