Abstract
The emergence of antimicrobial resistance has generated global concerns regarding many pathogenic microorganisms, such as methicillin-resistant Staphylococcus aureus. The inhibition of microbial molecular targets by natural products has led to the discovery of new paths capable of reverting resistance to classical antimicrobial agents. Neocalyptrocalyx longifolium (Mart.) Cornejo & Iltis, Capparaceae, is a Brazilian medicinal plant indicated for the treatment of skin and respiratory tract bacterial infections. Nevertheless, few studies have investigated its chemical composition. In view of the current development of pathogenic microorganism resistance, the isolation and identification of efflux pumps inhibitors from the roots of N. longifolium is described herein. In addition, the elements that contribute to substrate binding and inhibition of the MsrA protein, an ABC-type transporter, were analyzed based on in silico experiments. Five substances were isolated and characterized by NMR and HRMS. Four of them exhibited interesting structural features, composed of 1,3-oxazolidine-2-thione and 1,3-oxazolidine-2-one cores. 5-Methyl-5-ethyl-oxazolidine-2-one, an undescribed natural product, inhibited the activity of the MsrA transporter and, therefore, the potency of erythromycin was increased. Docking analysis revealed specific hydrogen interactions for this inhibitor at the MsrA ATP binding site.
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Acknowledgements
The authors gratefully acknowledge Dr. Simon Gibbons (The School of Pharmacy, University of London) for kindly provide the MSRA strains.
Funding
This work was supported by Coordenação de Aperfeiçoamento do Pessoal de Nível Superior (CAPES, Finance Code 001) and Fianciadora de Estudos e Projetos (FINEP) by means of INCT-RENNOFITO.
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TAS: contributed designing the study, analyzing data and writing the manuscript first draft; JPRS: acquisition of data; JIMM: acquisition of data (identification of botanical material); DFR, NHB, JPS: acquisition and analysis of biological essays; CH, RPM, MTS: analysis and interpretation of in silico data; LSA, JFT: critically revised the manuscript; MSS: final approval of the version to be submitted.
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de Souza, T.A., Silva, J.P.R., Rodrigues, D.F. et al. Oxazolidines from Neocalyptrocalyx longifolium Inhibit MsrA Protein in Methicillin Resistant Staphylococcus aureus. Rev. Bras. Farmacogn. 33, 1084–1088 (2023). https://doi.org/10.1007/s43450-023-00422-6
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DOI: https://doi.org/10.1007/s43450-023-00422-6