Análise estereoquímica dos alcaloides piperidínicos isolados de Senna spectabilis e avaliação do potencial anticolinesterásico

Abstract

Natural products have been used since ancient times as a way to cure or prevent human illness. Throughout history, compounds obtained from natural sources have aroused great interest due to the complexity of molecular arrangements associated with the three-dimensional dispositions of asymmetric carbons and your biological activities. Thus, for a long time, synthetic drugs were inspired by the structures of natural compounds, frequently chirals, which were produced in the form of racemates, ignoring the possible differences in biological activity that different stereoisomers could cause. Against this background, we have invested in the study of piperidine alkaloids present in Senna spectabilis, which have stereogenic centers and verified action on the central nervous system, as well as presenting various biological activities such as leishmanicide, antimalarial and anticholinesterase. In this sense, the present study describes the isolation process of chiral piperidine alkaloids from the ethanolic extract of Senna spectabilis flowers. This extract was submitted to liquid-liquid extraction with hexane and dichloromethane, being the second fraction with the highest concentration of alkaloids. This fraction was submitted to different chromatographic procedures, from which homologues 1 and 2, previously described in S. spectabilis, were isolated, as well as the two new homologous compounds, whose chromatographic and spectrometric analyzes indicate that they are diastereoisomers of 1 and 2. Then, the mixture containing 4 and 5 was subjected to an esterification reaction with acetyl chloride, obtaining compound 60. The natural and semi-synthetic compounds were evaluated in the acetylcholinesterase (AChE) inhibition test, where it was possible to observe that homologous alkaloids 1 (IC50 0.62 ± 0.01 ug/mL) and 2 (IC50 0.87 ± 0.12 ug/mL), with the same stereochemistry are more potent than the respective stereoisomers 4 (IC50 6.49 ± 0.23 ug/mL) and 5 (IC50 17.60 ± 1.90 ug/mL). These compounds exhibited an AChE inhibition potential of the same order of magnitude as the positive control, galantamine (IC50 1.50 ± 0.10 ug/mL), however the semi-synthetic derivative 60 was considered inactive (IC50 > 300.00 ug/mL).