Structural characterization, hepatoprotective activity and in vitro metabolism of 3-aminospirostanes alkaloids from roots of Solanum paniculatum L. (Solanaceae)

Author(s)

Matheus Coutinho Gazolla

• Document type: Master's Dissertation
• Press: Ribeirão Preto.
• Institution: Universidade de São Paulo (USP). Faculdade de Ciências Farmacêuticas de Ribeirão Preto (PCARP/BC)
• Defense date: 2020-06-22

Examining board members

Norberto Peporine Lopes; João Carlos Palazzo de Mello; Wagner Ferreira dos Santos

• Advisor: Norberto Peporine Lopes; Lucas Maciel Mauriz Marques

Abstract

The species Solanum paniculatum L. is popularly known as jurubeba and used in Brazilian folk medicine to treat gastric disorders and prevent liver disease. The production of steroidal alkaloids is remarkable in plants of the genus Solanum and in this species the 3-aminospirostanes stand out. Although several biological activities are attributed to this species, studies that address phytochemistry and medicinal properties specifically of 3-aminospirostanes are rare. Knowledge of the toxicology of this class is also scarce and in vitro test models have been widely applied and when associated with structural determination techniques such as mass spectrometry, they provide reliable information about the possible products generated. In this context, this work aimed to characterize and propose the main gas electrospray fragmentation pathways of steroidal alkaloids 3-aminospirostanes, perform tests of hepatoprotective activity in vivo and evaluate the possible metabolites formed through the reactions that mimic the oxidation by the system cytochrome P-450, using biomimetic catalysts and by biotransformation using rat microsomes. The jurubeba roots were collected, dried and submitted to maceration, obtaining the crude extract (SP-EB). An acid-base extraction was performed, resulting in the enriched fraction of alkaloids (SP-FA). From this fraction, seven steroidal alkaloids of the class 3-aminospirostane were identified, four of them unpublished. With the aid of computational chemistry, the entire gas-phase fragmentation profile of this class was defined. SP-EB and SP-FA were evaluated for hepatoprotection in vivo, showing promising results. Through chromatographic techniques, the isolation of jurubidine was performed, which when analyzed in in vitro metabolism assays showed the formation of a putative metabolite in the presence of iodozilbenzene. This work provided the discovery of four new substances and contributes to mass spectrometry studies for the class of 3-aminospirostanes. In addition, it proves the hepatoprotective activity of this species and lays the foundations for a better understanding of the metabolism of steroidal alkaloids. (AU)

• FAPESP's process: 17/19330-1 - In vitro metabolism of steroidal alkaloids from Solanum paniculatum l. (Solanaceae)
• Grantee: Matheus Coutinho Gazolla
• Support Opportunities: Scholarships in Brazil - Master