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

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Mendes, Leia da C. ; Dantas, Thais B. Vieira ; Severino, Richele P. ; da Silva, Larissa Ramos G. ; de Souza, Dulce H. F. ; Cass, Quezia B. ; Ramalho, Suelem D. ; Vieira, Paulo C. ; de Souza, Guilherme E. ; Guido, Rafael V. C. ; Urschel, Marie-Kathrin ; Kersten, Christian ; de Sousa, Lorena R. F.

• Document type: Journal article
• Source: MEDICINAL CHEMISTRY RESEARCH; v. 32, n. 10, p. 11-pg., 2023-07-24.

Abstract

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. IC50 values of 13.6 and 8.0 mu g/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 IC50 values were 175.9 +/- 16.9 and 4.72 +/- 0.57 mu M, 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. [GRAPHICS] . (AU)

• FAPESP's process: 13/07600-3 - CIBFar - Center for Innovation in Biodiversity and Drug Discovery
• Grantee: Glaucius Oliva
• Support Opportunities: Research Grants - Research, Innovation and Dissemination Centers - RIDC
• FAPESP's process: 20/12904-5 - Discovery of Plasmodium falciparum inhibitors from Cerrado plants as lead compounds candidates for malaria: integrated studies of ultra-efficient chromatography, spectroscopy, and biological assays
• Grantee: Rafael Victorio Carvalho Guido
• Support Opportunities: BIOTA-FAPESP Program - Regular Research Grants