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Article

Phytochemical Characterization of Schinus terebinthifolia Leaf Phytobiotics and Their Potential as Natural Antibiotic Adjuvants Against Carbapenem-Resistant Bacteria

by
Fatima Mourabiti
1,*,
Fatimazahra Jouga
1,
José Luis Rodríguez Rama
2,
Abdelhakim Elmakssoudi
3,
Souraya Sakoui
1,
Lorena G. Calvo
2,
Abdelaziz Soukri
1,
Trinidad de Miguel
2 and
Bouchra El Khalfi
1,*
1
Laboratory of Health, Environment and Biotechnology, Team of Physiopathology, Molecular Genetics and Biotechnology, Faculty of Sciences Ain Chock, Hassan II University of Casablanca, Casablanca 20100, Morocco
2
Department of Microbiology and Parasitology, Universidade de Santiago de Compostela, E-15782 Santiago de Compostela, Spain
3
Laboratory of Molecular Synthesis, Extraction Valorization, Faculty of Sciences Ain Chock, Hassan II University of Casablanca, Casablanca 20100, Morocco
*
Authors to whom correspondence should be addressed.
Appl. Sci. 2026, 16(18), 9212; https://doi.org/10.3390/app16189212
Submission received: 10 August 2026 / Revised: 10 September 2026 / Accepted: 11 September 2026 / Published: 17 September 2026
(This article belongs to the Special Issue Synthesis and Biological Evaluation of New Compounds)

Abstract

The emergence of carbapenem-resistant Gram-negative bacteria has intensified the search for natural compounds capable of restoring antibiotic efficacy by targeting β-lactamase-mediated resistance. This study investigated the antibacterial, β-lactamase inhibitory, and in silico potential of Schinus terebinthifolia leaf phytobiotics. Soxhlet (STS), maceration (STM), and essential oil (STEOL) extracts were evaluated against carbapenem-resistant Escherichia coli, Klebsiella pneumoniae, and Pseudomonas aeruginosa using agar diffusion, broth microdilution, checkerboard, and colorimetric β-lactamase inhibition assays. In parallel, the phytochemicals identified by GC–MS and LC–MS were virtually screened against the VIM and OXA-48-like β-lactamases using PyRx, followed by drug-likeness prediction using SwissADME. All phytobiotics exhibited significant antibacterial activity and synergistically enhanced the efficacy of cefotaxime against the majority of the tested bacterial strains (ΣFICI ≤ 0.5). Moreover, they markedly inhibited β-lactamase activity, with complete inhibition achieved at MIC/2. Among the tested phytobiotics, STS exhibited the greatest β-lactamase inhibitory potency, with an IC50 of 49.8 μg/mL. Virtual screening identified diosmetin, catechin, quercetin, ellagic acid, and epicatechin gallate as the most promising candidate β-lactamase inhibitors, exhibiting strong binding affinities toward VIM and OXA-48-like β-lactamases. SwissADME analysis further indicated favorable drug-like properties for the top-ranked compounds. Collectively, these findings suggest that S. terebinthifolia phytobiotics have promising antibacterial and β-lactamase-inhibitory potential and may represent a source of candidate compounds for further investigation as antibiotic adjuvants against carbapenem-resistant Gram-negative pathogens.
Keywords: β-lactamase inhibition; cefotaxime; antibiotic potentiation; Schinus terebinthifolia; carbapenem resistance; molecular docking; virtual screening; drug-likeness prediction; phytochemicals β-lactamase inhibition; cefotaxime; antibiotic potentiation; Schinus terebinthifolia; carbapenem resistance; molecular docking; virtual screening; drug-likeness prediction; phytochemicals

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MDPI and ACS Style

Mourabiti, F.; Jouga, F.; Rama, J.L.R.; Elmakssoudi, A.; Sakoui, S.; Calvo, L.G.; Soukri, A.; de Miguel, T.; Khalfi, B.E. Phytochemical Characterization of Schinus terebinthifolia Leaf Phytobiotics and Their Potential as Natural Antibiotic Adjuvants Against Carbapenem-Resistant Bacteria. Appl. Sci. 2026, 16, 9212. https://doi.org/10.3390/app16189212

AMA Style

Mourabiti F, Jouga F, Rama JLR, Elmakssoudi A, Sakoui S, Calvo LG, Soukri A, de Miguel T, Khalfi BE. Phytochemical Characterization of Schinus terebinthifolia Leaf Phytobiotics and Their Potential as Natural Antibiotic Adjuvants Against Carbapenem-Resistant Bacteria. Applied Sciences. 2026; 16(18):9212. https://doi.org/10.3390/app16189212

Chicago/Turabian Style

Mourabiti, Fatima, Fatimazahra Jouga, José Luis Rodríguez Rama, Abdelhakim Elmakssoudi, Souraya Sakoui, Lorena G. Calvo, Abdelaziz Soukri, Trinidad de Miguel, and Bouchra El Khalfi. 2026. "Phytochemical Characterization of Schinus terebinthifolia Leaf Phytobiotics and Their Potential as Natural Antibiotic Adjuvants Against Carbapenem-Resistant Bacteria" Applied Sciences 16, no. 18: 9212. https://doi.org/10.3390/app16189212

APA Style

Mourabiti, F., Jouga, F., Rama, J. L. R., Elmakssoudi, A., Sakoui, S., Calvo, L. G., Soukri, A., de Miguel, T., & Khalfi, B. E. (2026). Phytochemical Characterization of Schinus terebinthifolia Leaf Phytobiotics and Their Potential as Natural Antibiotic Adjuvants Against Carbapenem-Resistant Bacteria. Applied Sciences, 16(18), 9212. https://doi.org/10.3390/app16189212

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