Alcaloides e diidrochalconas de Metrodorea stipularis: química e bioatividade

Abstract

This work was based on bioactivity-guided study of five plants ( Galipea jasminiflora , Esenbeckia febrifuga, Esenbeckia grandiflora , Metrodorea stipularis and Zanthoxylum Fagara ) from Rutaceae family using the enzyme cruzain from Trypanosoma cruzi as target. The dichlorometane liquid-liquid partition from stems of M. stipularis were the most active one, and after a chromatographic study its fractions showed high enzymatic inhibition, so all fractions were submitted a chromatographic study aiming to isolate the secondary metabolites responsible for this inhibition. A number of compounds were isolated, among them: seven alkaloids , six coumarins, one steroid, and four dihydrochalcones, two alkaloids and three dihydrochalcones have been described for the first time. It was observed the presence of the dihydrochalcones in all active fractions indicating that has of compounds may be responsible for the activity of the extracts against cruzain. Due to the similarity of the cruzain with cathespsins B and L, and to further explore the bioactivity the isolated metabolites were also assayed in these enzymes. Four alkaloids as well two dihydrochalcones showed significant inhibition of cathepsin B, while dihydrochalcones showed to inhibition cathepsin L. Plants of this family are used in folk medicine for the treatment of malaria , so these compounds were also tested against Plasmodium falciparum parasite, and good activity was found for two dihydrochalcones.