{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,20]],"date-time":"2026-05-20T15:33:08Z","timestamp":1779291188257,"version":"3.51.4"},"reference-count":33,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2023,5,15]],"date-time":"2023-05-15T00:00:00Z","timestamp":1684108800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"MU University, INSERM, Campus France and the French Embassy"},{"name":"AMU University and INSERM"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The continuous emergence of bacterial resistance alters the activities of different antibiotic families and requires appropriate strategies to solve therapeutic impasses. Medicinal plants are an attractive source for researching alternative and original therapeutic molecules. In this study, the fractionation of natural extracts from A. senegal and the determination of antibacterial activities are associated with molecular networking and tandem mass spectrometry (MS\/MS) data used to characterize active molecule(s). The activities of the combinations, which included various fractions plus an antibiotic, were investigated using the \u201cchessboard\u201d test. Bio-guided fractionation allowed the authors to obtain individually active or synergistic fractions with chloramphenicol activity. An LC-MS\/MS analysis of the fraction of interest and molecular array reorganization showed that most identified compounds are Budmunchiamines (macrocyclic alkaloids). This study describes an interesting source of bioactive secondary metabolites structurally related to Budmunchiamines that are able to rejuvenate a significant chloramphenicol activity in strains that produce an AcrB efflux pump. They will pave the way for researching new active molecules for restoring the activity of antibiotics that are substrates of efflux pumps in enterobacterial-resistant strains.<\/jats:p>","DOI":"10.3390\/ijms24108790","type":"journal-article","created":{"date-parts":[[2023,5,16]],"date-time":"2023-05-16T02:37:51Z","timestamp":1684204671000},"page":"8790","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Acacia senegal Budmunchiamines as a Potential Adjuvant for Rejuvenating Phenicol Activities towards Escherichia coli-Resistant Strains"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4643-8369","authenticated-orcid":false,"given":"Ren\u00e9","family":"Dofini Magnini","sequence":"first","affiliation":[{"name":"UMR_MD1, U-1261, INSERM, SSA, IRBA, MCT, Facult\u00e9 de Pharmacie, Universit\u00e9 Aix-Marseille, 13385 Marseille, France"},{"name":"Laboratoire de Recherche-D\u00e9veloppement de Phytom\u00e9dicaments et M\u00e9dicaments (LR-D\/PM), IRSS, CNRST, D\u00e9partement MEPHATRA-PH, Ouagadougou 03 BP 7047, Burkina Faso"},{"name":"Laboratoire de Biochimie et de Chimie Appliqu\u00e9e (LABIOCA), Universit\u00e9 Joseph Ki-Zerbo, Ouagadougou 03 BP 7021, Burkina Faso"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-6556-8339","authenticated-orcid":false,"given":"Fran\u00e7ois","family":"Pedinielli","sequence":"additional","affiliation":[{"name":"Institut de Chimie Mol\u00e9culaire de Reims, UMR CNRS 7312, Universit\u00e9 Reims-Champagne-Ardenne, UFR Sciences, BP 1039, CEDEX 2, 51687 Reims, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3253-6275","authenticated-orcid":false,"given":"Julia","family":"Vergalli","sequence":"additional","affiliation":[{"name":"UMR_MD1, U-1261, INSERM, SSA, IRBA, MCT, Facult\u00e9 de Pharmacie, Universit\u00e9 Aix-Marseille, 13385 Marseille, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Noufou","family":"Ouedraogo","sequence":"additional","affiliation":[{"name":"Laboratoire de Recherche-D\u00e9veloppement de Phytom\u00e9dicaments et M\u00e9dicaments (LR-D\/PM), IRSS, CNRST, D\u00e9partement MEPHATRA-PH, Ouagadougou 03 BP 7047, Burkina Faso"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Simon","family":"Remy","sequence":"additional","affiliation":[{"name":"Institut de Chimie Mol\u00e9culaire de Reims, UMR CNRS 7312, Universit\u00e9 Reims-Champagne-Ardenne, UFR Sciences, BP 1039, CEDEX 2, 51687 Reims, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Adama","family":"Hilou","sequence":"additional","affiliation":[{"name":"Laboratoire de Biochimie et de Chimie Appliqu\u00e9e (LABIOCA), Universit\u00e9 Joseph Ki-Zerbo, Ouagadougou 03 BP 7021, Burkina Faso"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9355-8980","authenticated-orcid":false,"given":"Jean-Michel","family":"Brunel","sequence":"additional","affiliation":[{"name":"UMR_MD1, U-1261, INSERM, SSA, IRBA, MCT, Facult\u00e9 de Pharmacie, Universit\u00e9 Aix-Marseille, 13385 Marseille, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7092-7977","authenticated-orcid":false,"given":"Jean-Marie","family":"Pag\u00e8s","sequence":"additional","affiliation":[{"name":"UMR_MD1, U-1261, INSERM, SSA, IRBA, MCT, Facult\u00e9 de Pharmacie, Universit\u00e9 Aix-Marseille, 13385 Marseille, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5040-8379","authenticated-orcid":false,"given":"Anne","family":"Davin-Regli","sequence":"additional","affiliation":[{"name":"UMR_MD1, U-1261, INSERM, SSA, IRBA, MCT, Facult\u00e9 de Pharmacie, Universit\u00e9 Aix-Marseille, 13385 Marseille, France"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,5,15]]},"reference":[{"key":"ref_1","unstructured":"CDC (2019). Antibiotic Resistance Threats in the United States, 2019."},{"key":"ref_2","unstructured":"OMS (2022). Global Antimicrobial Resistance and Use Surveillance System (GLASS) Report 2022."},{"key":"ref_3","unstructured":"O\u2019Neill, J. (2016). Tackling Drug-Resistant Infections Globally: Final Report and Recommendations."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"17001","DOI":"10.1038\/nmicrobiol.2017.1","article-title":"Mechanisms of Envelope Permeability and Antibiotic Influx and Efflux in Gram-Negative Bacteria","volume":"2","author":"Masi","year":"2017","journal-title":"Nat. Microbiol."},{"key":"ref_5","unstructured":"OMS (2019). Who Global Report on Traditional and Complementary Medicine 2019."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Lomartire, S., and Gon\u00e7alves, A.M.M. (2023). An Overview on Antimicrobial Potential of Edible Terrestrial Plants and Marine Macroalgae Rhodophyta and Chlorophyta Extracts. Mar. Drugs, 21.","DOI":"10.3390\/md21030163"},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Magnini, R.D., Hilou, A., Millogo-Kon\u00e9, H., Pag\u00e8s, J.-M., and Davin-Regli, A. (2020). Acacia Senegal Extract Rejuvenates the Activity of Phenicols on Selected Enterobacteriaceae Multi Drug Resistant Strains. Antibiotics, 9.","DOI":"10.3390\/antibiotics9060323"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Tabcheh, J., Vergalli, J., Davin-R\u00e9gli, A., Ghanem, N., Pag\u00e8s, J.-M., Al-Bayssari, C., and Brunel, J.-M. (2023). Rejuvenating the Activity of Usual Antibiotics on Resistant Gram-Negative Bacteria: Recent Issues and Perspectives. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24021515"},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Magnini, R.D., Niti\u00e9ma, M., Ou\u00e9draogo, G.G., Ilboudo, S., Banc\u00e9, A., Millogo-Kon\u00e9, H., Giorgio, C.D., Pag\u00e8s, J.-M., Hilou, A., and Davin-Regli, A. (2021). Toxicity and Bacterial Anti-Motility Activities of the Hydroethanolic Extract of Acacia senegal (L.) Willd (Fabaceae) Leaves. BMC Complement. Med. Ther., 21.","DOI":"10.1186\/s12906-021-03348-5"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"2955","DOI":"10.1021\/ac403223f","article-title":"Identification of Natural Metabolites in Mixture: A Pattern Recognition Strategy Based on (13)C NMR","volume":"86","author":"Hubert","year":"2014","journal-title":"Anal. Chem."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1536","DOI":"10.1021\/ac026203i","article-title":"Advancing NMR Sensitivity for LC-NMR-MS Using a Cryoflow Probe: Application to the Analysis of Acetaminophen Metabolites in Urine","volume":"75","author":"Spraul","year":"2003","journal-title":"Anal. Chem."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"624","DOI":"10.1016\/S1359-6446(03)02749-1","article-title":"LC-NMR-MS in Drug Discovery","volume":"8","author":"Corcoran","year":"2003","journal-title":"Drug Discov. Today"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1016\/S0021-9673(04)01449-9","article-title":"Characterization of a Paracetamol Metabolite Using On-Line LC-SPE-NMR-MS and a Cryogenic NMR Probe","volume":"1058","author":"Godejohann","year":"2004","journal-title":"J. Chromatogr. A"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1016\/0031-9422(94)00829-I","article-title":"N-Demethyl Budmunchiamines from Albizzia Lebbek Seeds","volume":"39","author":"Misra","year":"1995","journal-title":"Phytochemistry"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1036","DOI":"10.1021\/np9602067","article-title":"Macrocyclic Budmunchiamine Alkaloids from Albizia Lebbek","volume":"60","author":"Dixit","year":"1997","journal-title":"J. Nat. Prod."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1016\/S0031-9422(02)00081-X","article-title":"Spermine Alkaloids from Albizia Adinocephala with Activity against Plasmodium Falciparum Plasmepsin II","volume":"60","author":"Ovenden","year":"2002","journal-title":"Phytochemistry"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1522","DOI":"10.1021\/np50078a006","article-title":"DNA as an Affinity Probe Useful in the Detection and Isolation of Biologically Active Natural Products","volume":"54","author":"Pezzuto","year":"1991","journal-title":"J. Nat. Prod."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1795","DOI":"10.1016\/0031-9422(92)83150-W","article-title":"Budmunchiamines D\u2013I from Albizia Amara","volume":"31","author":"Pezzuto","year":"1992","journal-title":"Phytochemistry"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"850","DOI":"10.1021\/np960397d","article-title":"New Macrocyclic Spermine (Budmunchiamine) Alkaloids from Albizia Gummifera: With Some Observations on the Structure\u2014Activity Relationships of the Budmunchiamines","volume":"59","author":"Rukunga","year":"1996","journal-title":"J. Nat. Prod."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1531","DOI":"10.1021\/np50078a007","article-title":"Biological Activity of Novel Macrocyclic Alkaloids (Budmunchiamines) from Albizia Amara Detected on the Basis of Interaction with DNA","volume":"54","author":"Mar","year":"1991","journal-title":"J. Nat. Prod."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"438","DOI":"10.1080\/10496475.2014.996695","article-title":"Evaluation of Antimicrobial and Antioxidant Properties of Pithecolobine Isolated from Albizia Saman","volume":"21","author":"Thippeswamy","year":"2015","journal-title":"J. Herbs Spices Med. Plants"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1007\/s00003-013-0839-7","article-title":"Efficacy of Bioactive Compounds Isolated from Albizia Amara and Albizia Saman as Source of Antifungal and Antiaflatoxigenic Agents","volume":"8","author":"Thippeswamy","year":"2013","journal-title":"J. Verbr. Lebensm."},{"key":"ref_23","first-page":"791","article-title":"Antimicrobial, Antiparasitic and Cytotoxic Spermine Alkaloids from Albizia Schimperiana","volume":"4","author":"Samoylenko","year":"2009","journal-title":"Nat. Prod. Commun."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Boes, A., Brunel, J.M., Derouaux, A., Kerff, F., Bouhss, A., Touze, T., Breukink, E., and Terrak, M. (2020). Squalamine and Aminosterol Mimics Inhibit the Peptidoglycan Glycosyltransferase Activity of PBP1b. Antibiotics, 9.","DOI":"10.3390\/antibiotics9070373"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"276","DOI":"10.1002\/cbic.201600532","article-title":"Motuporamine Derivatives as Antimicrobial Agents and Antibiotic Enhancers against Resistant Gram-Negative Bacteria","volume":"18","author":"Borselli","year":"2017","journal-title":"ChemBioChem"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"3163","DOI":"10.1016\/j.bmc.2015.04.069","article-title":"Synthesis and Antimicrobial Activity of Chloramphenicol-Polyamine Conjugates","volume":"23","author":"Magoulas","year":"2015","journal-title":"Bioorg. Med. Chem."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"198","DOI":"10.1038\/s42003-020-0929-x","article-title":"The Challenge of Intracellular Antibiotic Accumulation, a Function of Fluoroquinolone Influx versus Bacterial Efflux","volume":"3","author":"Vergalli","year":"2020","journal-title":"Commun. Biol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"9821","DOI":"10.1038\/s41598-017-08775-4","article-title":"Fluoroquinolone Structure and Translocation Flux across Bacterial Membrane","volume":"7","author":"Vergalli","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"464","DOI":"10.1016\/j.phymed.2011.12.003","article-title":"Antibacterial Activity of Thymus Maroccanus and Thymus Broussonetii Essential Oils against Nosocomial Infection\u2013Bacteria and Their Synergistic Potential with Antibiotics","volume":"19","author":"Fadli","year":"2012","journal-title":"Phytomedicine"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1016\/j.tips.2016.10.011","article-title":"Molecular Networking As a Drug Discovery, Drug Metabolism, and Precision Medicine Strategy","volume":"38","author":"Quinn","year":"2017","journal-title":"Trends Pharmacol. Sci."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1016\/S1570-0232(02)00746-8","article-title":"Overexpression and Purification of the Three Components of the Enterobacter Aerogenes AcrA\u2013AcrB\u2013TolC Multidrug Efflux Pump","volume":"786","author":"Masi","year":"2003","journal-title":"J. Chromatogr. B"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"3003","DOI":"10.1099\/00221287-144-11-3003","article-title":"Porin Alteration and Active Efflux: Two in Vivo Drug Resistance Strategies Used by Enterobacter Aerogenes","volume":"144","author":"Mallea","year":"1998","journal-title":"Microbiology"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1113","DOI":"10.1016\/j.bbrc.2005.01.069","article-title":"Chloramphenicol and Expression of Multidrug Efflux Pump in Enterobacter Aerogenes","volume":"328","author":"Ghisalberti","year":"2005","journal-title":"Biochem. Biophys. Res. Commun."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/10\/8790\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T19:35:26Z","timestamp":1760124926000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/10\/8790"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,5,15]]},"references-count":33,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2023,5]]}},"alternative-id":["ijms24108790"],"URL":"https:\/\/doi.org\/10.3390\/ijms24108790","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,5,15]]}}}