Alcaloides do gênero crotalaria: isolamento, elucidação estrutural, síntese de derivados e potencial biológico

Abstract

Crotalaria is widespread in tropical areas mainly in Argentina and Brazil. Two species of Crotalaria: Crotalaria retusa and Crotalaria pallida could be found in Rio Grande do Norte, Brazil. The aim of this study is to obtain extracts containing alkaloids as well as the isolation and structural characterization of these metabolites. In addition, the potential of the pyrrolizidine alkaloids obtained was evaluated regarding biological properties and synthesis of derivatives. The extracts were prepared by exhaustive maceration with ethanol 96%. The crude extract was subjected to an acid-base extraction to obtain alkaloids-enriched fractions. Additional purification procedures afforded monocrotaline from C. retusa and pallidine from C. pallida. Monocrotaline was submitted to synthesis of two derivatives: retronecine and azide-retronecine. The activity against T. vaginalis was evaluated and the results indicated inhibition on parasite growth of 80% at 1 mg/mL neither cytotoxicity against vaginal epithelial cells nor hemolytic activity. On the other hand, retronecine showed no anti-T. vaginalis activity while azide-retronecine was more active than monocrotaline by killing 85% of the parasites at 1 mg/mL. Pallidine is an uncommon pyrrolizidine alkaloid that has important structural features. Furthermore, pallidine was evaluated against antibiofilm activity and demonstrated the ability to inhibit more than 50% of Staphylococcus epidermidis biofilm formation at 1mg/mL, without providing biocidal activity. It is an outstanding start point to develop new antibiofilm strategies. Finally, the pyrrolizidine alkaloids are suggested as promising prototypes for new drugs as well as our results suggests that the edaphoclimatic conditions of Rio Grande do Norte could affect the biosynthesis of these alkaloids and facilitate the occurrence of new chemical skeletons.