Diversidade química do gênero Metternichia J.C.Mikan e atividade anti-inflamatória de lignanamidas isoladas de Metternichia macrocalyx (SOLANACEAE)

Abstract

Phytochemical studies contribute to the development of new drugs, understanding of metabolic profile and chemotaxonomy. Among the plant families of greatest phytochemical interest is the Solanaceae family, known for its high biosynthetic capacity for alkaloids, along with other secondary metabolites such as saponins, lignanamides and flavonoids. The genus Metternichia J.C.Mikan is one of the taxonomically complex and relatively understudied chemically genera of the Solanaceae family. The taxon is formed by the species M. macrocalyx from the Caatinga and M. princeps from the Atlantic Forest, inhabiting contrasting ecological and floristic environments. Therefore, this study focused to establish the chemical profile of the genus Metternichia and evaluate the anti-inflammatory activity of lignanamides isolated from M. macrocalyx. In this work, the dried and pulverized extract of the roots of M. macrocalyx was subjected to maceration in 95% ethanol for 72 h (3 x 72 h). The crude ethanol extract (CEE) underwent to partitioning in hexane, chloroform and ethyl acetate to obtain the respective extracts. The chloroform extract was subjected to medium pressure liquid chromatography (CLMP) and size exclusion chromatography. The resulting fractions underwent to high performance liquid chromatography (HPLC) on an analytical and preparative scale to obtain 5 new lignanamides indicated as metternichiamides A-E, in addition to N 1 ,N5 ,N10

-Tri-p- coumaroyl-spermidine. All compounds tested reduced nitric oxide (NO) levels. In

cytokine quantification assays, only metternichiamide B did not significantly affect IL- 10 levels. Moreover, metternichiamides A-C and E also reduced IL-1β levels. These

results suggested the anti-inflammatory potential of these compounds. Additionally, the dried and powdered plant material of M. macrocalyx and M. princeps leaves were subjected to maceration in 95% ethanol for 72 h (3 x 72 h). The CEEs underwent to partitioning in hexane, chloroform and ethyl acetate to obtain the respective extracts. An ethyl acetate extract (2.0 g) of M. macrocalyx was fractionated by classical column chromatography (CC) on silica gel using hexane, ethyl acetate and methanol, followed by HPLC to isolate the major compounds quercetin-3-O-xylopyranosyl-(1→2)- rhamnopyranoside and kaempferol-3-O-xylopyranosyl-(1→2)-rhamnopyranoside.

Subsequently, analysis of the extracts of the leaves was performed by HPLC-IES- MS/MS. The data were analyzed in comparison with standards, MS/MS data from the

literature, with libraries from GNPS, Massbank, MassbankEU and Respect through MS-DIAL, in addition to molecular networking, leading to the annotation of 49 compounds of these species. Finally, the data were subjected to chemometric analyses to obtain the main differences and similarities between these chemical profiles. This work generated a chemotaxomic and pharmacological contribution to the genus Metternichia, through the establishment of the chemical profile of the two species of the genus and the discovery of new lignanamides with anti-inflammatory activity.