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

Arginase is a potential target of drugs against Leishmania spp. Natural products can be a source of arginase inhibitors. This study has investigated whether the bark and leaves of Drimys brasiliensis Miers (Winteraceae), a plant known for its antileishmanial effect, can inhibit Leishmania amazonensis arginase. IC 50 values of 13.6 and 8.0 μg/mL were obtained for the ethanolic extracts from D. 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 in D. 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. Compounds 3a and 3b inhibited L. amazonensis arginase in vitro; the IC 50 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 in D. brasiliensis bark and leaves. Graphical Abstract