Alcaloides de Abuta panurensis (Menispermaceae): potencial de inibição da acetilcolinesterase, atividade citotóxica e imunomoduladora

Abstract

Species of the genus Abuta (Menispermaceae) are known for their ethnobotanical and a wide range of pharmacological properties. This work is reported the phytochemical study and biological activity investigation of the specie Abuta panurensis (Menispermaceae). A chemical profile of leaves, branches and seeds of the A. panurensis was elaborated by spectrometric techniques. The alkaloid fraction from leaves and branches was analyzed by HPLC-DAD-MS/MS. Structures of the alkaloids were elucidated by a combination of 1D and 2D NMR spectroscopic and spectrometric techniques together with an in silico study. Acetylcholinesterase enzyme inhibition, cytotoxic, and immunomodulatory activity of alkaloids were evaluated by in vitro assays. Thirteen alkaloids (isoquinolines and amides) were tentatively identified, of which five (lindoldhamine isomer, stepharine, palmatine, 5-N-methylmaitenine and N-trans-feruloyltiramine) were isolated and reported for the first time for the specie. The presence of 5-N-methylmaytenine polyamine was reported for the first time in Menispermaceae family. As for the acetylcholinesterase enzyme inhibition, four alkaloids showed the inhibition potential with IC50 values ranging from 19.55 µM to 61.24 µM. In silico study of interactions of stepharine and 5-N-methylmaitenine alkaloids with the acetylcholinesterase enzyme, interleukins IL-6 and IL-8 showed that the compounds were able to bind effectively to the AChE enzyme active sites and to demonstrate affinity towards IL-6 and IL -8 proteins. The stepharine and 5-N-methylmaytenine revealed a cytotoxic activity against two tumor cell lines (K562 and U937) with the IC50 values in the range of 11.77 µM to 28.48 µM, the alkaloids were not cytotoxic to normal cells. Regarding the immunomodulatory activity, both alkaloids inhibited the IL-6 production at similar levels. Stepharine inhibited considerably the IL-8 production, when compared to 5-N-methylmaytenine that showed, however, a dose-dependent action.