The Roots of Deguelia nitidula as a Natural Antibacterial Source against Staphylococcus aureus Strains

Deguelia nitidula (Benth.) A.M.G.Azevedo & R.A.Camargo (Fabaceae) is an herbaceous plant distributed in the Brazilian Amazon, and it is called “raiz do sol” (sun roots). On Marajó Island, quilombola communities use its prepared roots to treat skin diseases commonly caused by fungi, viruses, and bacteria. Thus, in this study, the extract, and its fractions from D. nitidula roots were used to perform in vitro cytotoxic and antibacterial assays against Staphylococcus aureus strains. Thereafter, liquid chromatography–mass spectrometry (LC–MS) was used for the metabolite annotation process. The ethanolic extract of D. nitidula roots show significant bactericidal activity against S. aureus with IC50 82 μg.mL−1 and a selectivity index (SI) of 21.35. Furthermore, the SREFr2 and SREFr3 fractions show a potent bactericidal activity, i.e., MIC of 46.8 μg.mL−1 for both, and MBC of 375 and 93.7 μg.mL−1, respectively. As showcased, SREFr3 shows safe and effective antibacterial activity mainly in respect to the excellent selectivity index (SI = 82.06). On the other hand, SREFr2 shows low selectivity (SI = 6.8), which characterizes it as not safe for therapeutic use. Otherwise, due to a limited amount of reference MS2 spectra in public libraries, up to now, it was not possible to perform a complete metabolite annotation. Despite that, our antibacterial results for SREFr3 and correlated substructures of amino acid derivatives show that the roots of D. nitidula are a natural source of specialized metabolites, which can be isolated in the future, and then used as a support for further bio-guided research, as well as natural drug development.

[1]  L. Santos,et al.  Antibacterial Activity from Momordica charantia L. Leaves and Flavones Enriched Phase , 2022, Pharmaceutics.

[2]  M. D. da Silva,et al.  Margaritaria nobilis L.F. (Phyllanthaceae): Ethnopharmacology and Application of Computational Tools in the Annotation of Bioactive Molecules , 2022, Metabolites.

[3]  P. Dorrestein,et al.  Comparison of Cosine, Modified Cosine, and Neutral Loss Based Spectrum Alignment For Discovery of Structurally Related Molecules , 2022, bioRxiv.

[4]  Emma L. Schymanski,et al.  Open Access Repository-Scale Propagated Nearest Neighbor Suspect Spectral Library for Untargeted Metabolomics , 2022, bioRxiv.

[5]  Milton Silva,et al.  Chemical Composition of Leaves, Stem, and Roots of Peperomia pellucida (L.) Kunth , 2022, Molecules.

[6]  C. Benevides,et al.  Ethnopharmacological studies in 21st century Brazil: a systematic review , 2022, Research, Society and Development.

[7]  Z. Zakaria,et al.  Antibacterial Effects of Flavonoids and Their Structure-Activity Relationship Study: A Comparative Interpretation , 2022, Molecules.

[8]  F. Bucar,et al.  Flavonoids as Inhibitors of Bacterial Efflux Pumps , 2021, Molecules.

[9]  Andrzej S. Skwarecki,et al.  Amino Acid Based Antimicrobial Agents – Synthesis and Properties , 2021, ChemMedChem.

[10]  M. Eberlin,et al.  Feature-Based Molecular Network-Guided Dereplication of Natural Bioactive Products from Leaves of Stryphnodendron pulcherrimum (Willd.) Hochr , 2021, Metabolites.

[11]  Shyi-Long Lee,et al.  Atomistic simulation on flavonoids derivatives as potential inhibitors of bacterial gyrase of Staphylococcus aureus , 2020, Journal of biomolecular structure & dynamics.

[12]  S. Brandão,et al.  Severe COVID-19: understanding the role of immunity, endothelium, and coagulation in clinical practice , 2020, Jornal vascular brasileiro.

[13]  E. Undurraga,et al.  Socioeconomic factors associated with antimicrobial resistance of Pseudomonas aeruginosa, Staphylococcus aureus, and Escherichia coli in Chilean hospitals (2008–2017) , 2020, Revista panamericana de salud publica = Pan American journal of public health.

[14]  Tim Cushnie,et al.  Bioprospecting for Antibacterial Drugs: a Multidisciplinary Perspective on Natural Product Source Material, Bioassay Selection and Avoidable Pitfalls , 2020, Pharmaceutical Research.

[15]  C. Wiart,et al.  Antibacterial activities of the extracts, fractions and isolated compounds from Canarium patentinervium Miq. against bacterial clinical isolates , 2020, BMC complementary medicine and therapies.

[16]  Christine M. Aceves,et al.  Reproducible molecular networking of untargeted mass spectrometry data using GNPS , 2019, Nature Protocols.

[17]  Juho Rousu,et al.  SIRIUS 4: a rapid tool for turning tandem mass spectra into metabolite structure information , 2019, Nature Methods.

[18]  R. Pathania,et al.  Efflux pump inhibitors for bacterial pathogens: From bench to bedside , 2019, The Indian journal of medical research.

[19]  N. Lima,et al.  Antifungal activity of extracts and phenolic compounds from Deguelia duckeana , 2018, Revista Brasileira de Farmacognosia.

[20]  J. Tamokou,et al.  Antimicrobial activities of flavonoid glycosides from Graptophyllum grandulosum and their mechanism of antibacterial action , 2018, BMC Complementary and Alternative Medicine.

[21]  J. Rachon,et al.  Synthesis and antimicrobial activity of amino acid and peptide derivatives of mycophenolic acid , 2017, European Journal of Medicinal Chemistry.

[22]  S. Cosgrove,et al.  Trends in Methicillin-Resistant Staphylococcus aureus Hospitalizations in the United States, 2010-2014 , 2017, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[23]  A. Amaral,et al.  Acaricidal activity of Derris floribunda essential oil and its main constituent , 2017 .

[24]  T. Foster Antibiotic resistance in Staphylococcus aureus. Current status and future prospects , 2017, FEMS microbiology reviews.

[25]  V. Kuete,et al.  Antimicrobial Activities of African Medicinal Spices and Vegetables , 2017 .

[26]  J. Sharifi‐Rad,et al.  The Search for Herbal Antibiotics: An In-Silico Investigation of Antibacterial Phytochemicals , 2016, Antibiotics.

[27]  Kristian Fog Nielsen,et al.  Sharing and community curation of mass spectrometry data with Global Natural Products Social Molecular Networking , 2016, Nature Biotechnology.

[28]  C. Alves,et al.  Using LC and Hierarchical Cluster Analysis as Tools to Distinguish Timbó Collections into Two Deguelia Species: A Contribution to Chemotaxonomy , 2016, Molecules.

[29]  F. Baquero,et al.  The global threat of antimicrobial resistance: science for intervention , 2015, New microbes and new infections.

[30]  M. Monteiro,et al.  Antimicrobial bioassay-guided fractionation of a methanol extract of Eupatorium triplinerve , 2015, Pharmaceutical biology.

[31]  M. Spiteller,et al.  Antimicrobial activity and cytotoxicity of the ethanol extract, fractions and eight compounds isolated from Eriosema robustum (Fabaceae) , 2013, BMC Complementary and Alternative Medicine.

[32]  J. Martins,et al.  Atividade biológica de extratos acetato de etila, etanólico e aquoso de timbó (Lonchocarpus floribundus) sobre carrapato bovino , 2013 .

[33]  M. N. D. Silva,et al.  Flavonoids from the leaves of Deguelia utilis (Leguminosae): structural elucidation and neuroprotective properties , 2012 .

[34]  Olga Genilloud,et al.  A New Approach to Drug Discovery , 2012, Journal of biomolecular screening.

[35]  M. Monteiro,et al.  Antifungal activity of some cyclooxygenase inhibitors on Candida albicans: PGE2-dependent mechanism , 2011, Folia Microbiologica.

[36]  A. G. Phadatare,et al.  Structure pre-requisites for isoflavones as effective antibacterial agents , 2011, Pharmacognosy reviews.

[37]  Matej Oresic,et al.  MZmine 2: Modular framework for processing, visualizing, and analyzing mass spectrometry-based molecular profile data , 2010, BMC Bioinformatics.

[38]  Y. Sultanbawa,et al.  An innovative microplate assay to facilitate the detection of antimicrobial activity in plant extracts. , 2009 .

[39]  Nigel W. Hardy,et al.  Proposed minimum reporting standards for chemical analysis , 2007, Metabolomics.

[40]  Neusa Santos de Queiroz A resistência bacteriana no contexto da infecção hospitalar , 2004 .

[41]  T. Mosmann Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. , 1983, Journal of immunological methods.

[42]  H. Morton,et al.  Staphylococcus aureus , 1948 .