(-)-5-Demethoxygrandisin B a New Lignan from Virola surinamensis (Rol.) Warb. Leaves: Evaluation of the Leishmanicidal Activity by In Vitro and In Silico Approaches.

Leishmaniasis is a complex disease caused by infection with different Leishmania parasites. The number of medications used for its treatment is still limited and the discovery of new drugs is a valuable approach. In this context, here we describe the in vitro leishmanicidal activity and the in silico interaction between trypanothione reductase (TryR) and (-)-5-demethoxygrandisin B from the leaves of Virola surinamensis (Rol.) Warb. The compound (-)-5-demethoxygrandisin B was isolated from V. surinamensis leaves, a plant found in the Brazilian Amazon, and it was characterized as (7R,8S,7'R,8'S)-3,4,5,3',4'-pentamethoxy-7,7'-epoxylignan. In vitro antileishmanial activity was examined against Leishmania amazonensis, covering both promastigote and intracellular amastigote phases. Cytotoxicity and nitrite production were gauged using BALB/c peritoneal macrophages. Moreover, transmission electron microscopy was applied to probe ultrastructural alterations, and flow cytometry assessed the shifts in the mitochondrial membrane potential. In silico methods such as molecular docking and molecular dynamics assessed the interaction between the most stable configuration of (-)-5-demethoxygrandisin B and TryR from L. infantum (PDB ID 2JK6). As a result, the (-)-5-demethoxygrandisin B was active against promastigote (IC50 7.0 µM) and intracellular amastigote (IC50 26.04 µM) forms of L. amazonensis, with acceptable selectivity indexes. (-)-5-demethoxygrandisin B caused ultrastructural changes in promastigotes, including mitochondrial swelling, altered kDNA patterns, vacuoles, vesicular structures, autophagosomes, and enlarged flagellar pockets. It reduced the mitochondria membrane potential and formed bonds with important residues in the TryR enzyme. The molecular dynamics simulations showed stability and favorable interaction with TryR. The compound targets L. amazonensis mitochondria via TryR enzyme inhibition.

Antibacterial Activity from Momordica charantia L. Leaves and Flavones Enriched Phase.

Momordica charantia L. (Cucurbitaceae) is a plant known in Brazil as "melão de São Caetano", which has been related to many therapeutic applications in folk medicine. Herein, we describe antibacterial activities and related metabolites for an extract and fractions obtained from the leaves of that species. An ethanolic extract and its three fractions were used to perform in vitro antibacterial assays. In addition, liquid chromatography coupled to mass spectrometry and the molecular networking approach were used for the metabolite annotation process. Overall, 25 compounds were annotated in the ethanolic extract from M. charantia leaves, including flavones, terpenes, organic acids, and inositol pyrophosphate derivatives. The ethanolic extract exhibited low activity against Proteus mirabilis (MIC 312.5 µg·mL-1) and Klebsiella pneumoniae (MIC 625 µg·mL-1). The ethyl acetate phase showed interesting antibacterial activity (MIC 156.2 µg·mL-1) against Klebsiella pneumoniae, and it was well justified by the high content of glycosylated flavones. Therefore, based on the ethyl acetate phase antibacterial result, we suggest that M. charantia leaves could be considered as an alternative antibacterial source against K. pneumoniae and can serve as a pillar for future studies as well as pharmacological application against the bacteria.