Estudo químico dos alcaloides piperidínicos presentes em Senna spectabilis (Fabaceae) e avaliação da atividade leishmanicida

Abstract

Brazil holds one of the greatest biodiversity on the planet and in this sense we cannot give up this privileged position for the chemical study of natural products for the discovery of new bioactive molecules. Along the national territory are six biomes that present a great diversity of plants. In this work, Senna spectabilis (Fabaceae) was selected for the chemical study because it presents 2,6-dialkyl-piperidin-3-ol type piperidine alkaloids, rare in nature and with great pharmacological potential. The study was carried out from the ethanolic extract of the flowers and the isolated compounds were submitted to the tests to evaluate the leishmanicidal activity and cytotoxicity. Initially, the ethanolic extract of S. spectabilis flowers was submitted to liquid-liquid extraction with n-hexane, chloroform and ethyl acetate. The fractions were analyzed by thin layer chromatography (TLC), where it was found that the chloroform fraction had a higher number of alkaloids with different Rfs. This fraction was subjected to column chromatography (CC), from which the mixture of (-)-cassine (1) and (-)- spectaline (6) homologues were obtained, which were separated by high performance liquid chromatography (HPLC) using light scattering detector. These compounds were submitted to nuclear magnetic resonance (NMR) experiments and high resolution mass spectrometry with electrospray ionization (ESI-MS) to determine their structures. During the chromatographic fractionation, two mixtures of homologous compounds (61a and 61b and 62a and 62b) were obtained, more polar than alkaloids 1 and 6. Due to the small amount of mass, these metabolites were identified by ESI-MS. Furthermore, a fraction with a mixture of alkaloids less polar than 1 and 6 was also obtained, which was subjected to preparative TLC, and was possible to obtain a mixture of the homologous alkaloids (-)-3-O-acetylcassine (13) and (-)- 3-O-acetylspectaline (14) which were separated by HPLC-light scattering. The isolated compounds were tested for leishmanicidal activity using strains of the parasite Leishmania amazoniensis, with 6 and 13 showing promising IC50 values ( IC50 15.81 ± 0.47 pg mL-1 e 30.25 ± 1.74 pg mL-1, respectively), when compared to the positive control amphotericin B (0.29 ± 0.01 pg mL-1). From the cytotoxicity assay, it was observed that alkaloid 6 presents some toxicity (CC50 66.67 ± 9.68 pg mL-1), but from the calculation of the selectivity index (SI), it was possible to verify that the evaluated compounds presented leishmanicidal activity at non-cytotoxic concentrations.