Using molecular networking and docking to explore arginase inhibitors among Drimys brasiliensis chemical constituents

This study has investigated whether the bark and leaves ofDrimys brasiliensis Miers (Winteraceae), a plant known for its antileishmanial effect, can inhibitLeishmania amazonensis arginase. IC50 values of 13.6 and 8.0  μg/mL were obtained for the ethanolic extracts fromD. brasiliensis bark and leaves, respectively. Liquid chromatography –high resolution mass spectrometry analysis of the bioactive extracts helped to identify ten compounds, including flavonoids, phenolic acids, and hydroxycinnamic acid derivatives. Among these compounds, flavonoids and chlorogenic acid are known for potentially inhibiting arginase, and the presence of flavonoids corroborates the leishmanicidal and antimalarial potential of the bioactive extracts. Tandem mass spectrometry (MS/MS), molecular networking and docking analysis (docking scores) showed that compounds commonly found inD. brasiliensis bark and leaves namely chlorogenic acid (2a) ( −11.94 kJ/mol), coumaroylquinic acid (2b) ( −13.45 kJ/mol), hydroxybenzaldehyde (3a) ( −9.95 kJ/mol), and dihydroxybenzoic acid (3b) ( −13.64 kJ/mol), might interact with arginase. Compounds3a and3b inhibitedL. amazonensis arginase in vitro; the IC50 values were 175.9  ± 16.9 and 4.72 ± 0.57 µM, respectively. Combining MS/MS and computational calculation of the bioactive extracts proved an effective strategy to identify bioactive compounds inD. brasiliensis bark and leaves.Graphical Abstract

Source: Medicinal Chemistry Research - July 24, 2023 Category: Chemistry Source Type: research