Síntese, caracterização e avaliação biológica de derivados da naringenina

Abstract

Naringenin (NAR) is an important flavonoid found in citrus fruits with broad biological properties, one of which is antiviral activity against dengue and Zika viruses. Despite its broad pharmacological spectrum, NAR exhibits poor bioavailability, a problem that prevents further clinical studies. To overcome this limitation, the functionalization of the flavonoid skeleton of NAR could modulate the physicochemical properties of the structure and achieve better biological properties. The insertion of lipophilic groups is able to improve permeability through the cell membrane and achieve a better biological response, as well as hydrophilic groups can increase solubility in the physiological environment. Thus, the replacement of NAR phenolic hydroxyls by different functional groups can delineate new drug candidate compounds. In the present work, 49 compounds were synthesized, among them some unpublished ones, in order to improve and potentiate the biological activity of NAR. Among the synthesized compounds, mono and dialkylated, mono and diacylated derivatives, oxime, mono and dihydroxyalkylated, mono and dialkyl brominated and 1,2,3- triazole derivatives were prepared. The alkylated and acylated derivatives underwent antitumor, anti-trichomonas vaginalis and antiviral evaluation against the Zika virus. NAR alkylated derivatives showed promising anti Zika activity, but with some cytotoxicity present for healthy mammalian cells.