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In this study, a new compound named tripterhyponoid A was found to effectively combat MRSA, with an MIC of 2.0 \u03bcg\/mL. It inhibited biofilm formation by downregulating genes related to the quorum sensing (QS) pathway (sarA, agrA, agrB, agrC, agrD, and hld) and eradicated mature biofilms. Furthermore, it induced DNA damage by binding to bacterial DNA, enhancing its efficiency against MRSA. Therefore, its anti-MRSA properties with multiple mechanisms of action make it less prone to developing resistance over 20 days. In addition, it reduced the bacterial load and regulated the levels of inflammatory cytokines IL-6 and IL-10 at the wound site in a mouse skin infection model. This paper provides the first in-depth investigation of the mechanisms of triterpenoids against MRSA by inhibiting the expression of QS system genes and binding to DNA.<\/jats:p>","DOI":"10.3390\/molecules30122539","type":"journal-article","created":{"date-parts":[[2025,6,10]],"date-time":"2025-06-10T09:59:14Z","timestamp":1749549554000},"page":"2539","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Tripterhyponoid A from Tripterygium hypoglaucum Inhibiting MRSA by Multiple Mechanisms"],"prefix":"10.3390","volume":"30","author":[{"given":"Yan-Yan","family":"Zhu","sequence":"first","affiliation":[{"name":"Yunnan Characteristic Plant Extraction Laboratory, Key Laboratory of Medicinal Chemistry for Natural Resource, Ministry of Education and Yunnan Province, School of Chemical Science and Technology, Yunnan University, Kunming 650500, 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bacterial antimicrobial resistance 1990-2021: A systematic analysis with forecasts to 2050","volume":"404","author":"Naghavi","year":"2024","journal-title":"Lancet"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Schilcher, K., and Horswill, A.R. (2020). Staphylococcal Biofilm Development Structure, Regulation, and Treatment Strategies. Microbiol. Mol. Biol. Rev., 84.","DOI":"10.1128\/MMBR.00026-19"},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Brooks, J.L., and Jefferson, K.K. (2014). Phase Variation of Poly-N-Acetylglucosamine Expression in Staphylococcus aureus. PLoS Pathog., 10.","DOI":"10.1371\/journal.ppat.1004292"},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Wang, J.H., Lu, X.Y., Wang, C.J., Yue, Y.J., Wei, B., Zhang, H.W., Wang, H., and Chen, J.W. (2024). Research Progress on the Combination of Quorum-Sensing Inhibitors and Antibiotics against Bacterial Resistance. Molecules, 29.","DOI":"10.3390\/molecules29071674"},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Jia, J., Zheng, M.X., Zhang, C.W., Li, B.L., Lu, C., Bai, Y.F., Tong, Q., Hang, X.D., Ge, Y.X., and Zeng, L.P. (2023). Killing of Staphylococcus aureus persisters by a multitarget natural product chrysomycin A. Sci. Adv., 9.","DOI":"10.1126\/sciadv.adg5995"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"20458","DOI":"10.1021\/acsami.3c03091","article-title":"Amphiphilic Nano-Swords for Direct Penetration and Eradication of Pathogenic Bacterial Biofilms","volume":"15","author":"Zhou","year":"2023","journal-title":"ACS Appl. Mater. Interfaces"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Bai, S.L., Wang, J.X., Yang, K.L., Zhou, C.L., Xu, Y.F., Song, J.F., Gu, Y.X., Chen, Z., Wang, M., and Shoen, C. (2021). A polymeric approach toward resistance-resistant antimicrobial agent with dual-selective mechanisms of action. Sci. Adv., 7.","DOI":"10.1126\/sciadv.abc9917"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1016\/j.jare.2023.04.017","article-title":"Antimicrobial activities of lavandulylated flavonoids in Sophora flavences against methicillin-resistant Staphylococcus aureus via membrane disruption","volume":"57","author":"Weng","year":"2024","journal-title":"J. Adv. Res."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Hamion, G., Aucher, W., Mercier, A., Tewes, F., Bertaux, J., Girardot, M., and Imbert, C. (2024). Insights into betulinic acid as a promising molecule to fight the interkingdom biofilm Staphylococcus aureus-Candida albicans. Int. J. Antimicrob. Agents, 63.","DOI":"10.1016\/j.ijantimicag.2024.107166"},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Gao, Y.D., Liu, S.S., Ma, Y.Z., Li, C.Z., Xiao, Z.H., Nie, S.L., and Tu, J. (2024). Effects of camellia saponins on biofilm formation and virulence factor genes of Bacillus cereus. LWT-Food Sci. Technol., 198.","DOI":"10.1016\/j.lwt.2024.116023"},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Zhu, Y.Y., Wang, Z.J., Zhu, M., Zhou, Z.S., Hu, B.Y., Wei, M.Z., Zhao, Y.L., Dai, Z., and Luo, X.D. (2024). A dual mechanism with H2S inhibition and membrane damage of morusin from Morus alba Linn. against MDR-MRSA. Bioorg. Med. Chem., 97.","DOI":"10.1016\/j.bmc.2023.117544"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"2366","DOI":"10.1021\/acs.jnatprod.4c00425","article-title":"Activity of the Caged Xanthone Morellic Acid against Vancomycin Resistant Enterococcus Infection by Targeting the Bacterial Membrane","volume":"87","author":"Tang","year":"2024","journal-title":"J. Nat. Prod."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"467","DOI":"10.1016\/j.jconrel.2024.09.028","article-title":"A new therapeutic strategy for infectious diseases against intracellular multidrug-resistant bacteria","volume":"375","author":"Wang","year":"2024","journal-title":"J. Control. Release"},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Lu, Q.Y., Wang, Z.J., Bai, L.Y., Zu, W.B., Zhou, Z.S., Zhu, Y.Y., Zhao, Y.L., and Luo, X.D. (2025). Diterpenoids of Caryopteris trichosphaera W. W. Sm. inhibiting MRSA and VRE in vitro and in vivo. J. Ethnopharmacol., 337.","DOI":"10.1016\/j.jep.2024.118805"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"3430","DOI":"10.1021\/acsinfecdis.4c00571","article-title":"6-Methoxyldihydrochelerythrine Chloride Inhibiting Intra and Extracellular Drug-Resistant Bacteria","volume":"10","author":"Bai","year":"2024","journal-title":"ACS Infect. Dis."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Shen, J.S., Wang, Z.J., Zhu, Y.Y., Wei, M.Z., Wang, X.H., and Luo, X.D. (2024). Antifungal bioactivity of Sarcococca hookeriana var. digyna Franch. against fluconazole-resistant Candida albicans in vitro and in vivo. J. Ethnopharmacol., 333.","DOI":"10.1016\/j.jep.2024.118473"},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Shi, Y.Z., Wang, Z.J., Shi, N., Bai, L.Y., Jiang, Y.M., Jiang, L., Liu, T., Wei, M.Z., Qin, M.L., and Luo, X.D. (2024). Anti-MRSA mechanism of spirostane saponin in Rohdea pachynema FT Wang & tang. J. Ethnopharmacol., 331.","DOI":"10.1016\/j.jep.2024.118327"},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Liu, T., Wang, Z.J., Shi, Y.Z., Tao, R., Huang, H., Zhao, Y.L., and Luo, X.D. (2024). Curcusinol from the fruit of Carex baccans with antibacterial activity against multidrug-resistant strains. J. Ethnopharmacol., 318.","DOI":"10.1016\/j.jep.2023.116892"},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Zheng, J.P., Hu, J.H., Yang, Y., Xiong, L., Yang, H.B., Zhang, Z.G., Jiang, N., and Liu, H.T. (2023). Suppressive effect of Tripterygium hypoglaucum (Levl.) Hutch extract on rheumatoid arthritis in mice by modulating inflammasome and bile acid metabolism. Biomed. Pharmacother., 167.","DOI":"10.1016\/j.biopha.2023.115494"},{"key":"ref_21","first-page":"730","article-title":"Tripterygium hypoglaucum extract ameliorates adjuvant-induced arthritis in mice through the gut microbiota","volume":"21","author":"Hu","year":"2023","journal-title":"Chin. J. Nat. Med."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Luo, H.Z., Xiang, J., Gui, W.Y., Gong, J.H., Zou, J.D., and Li, C.Y. (2024). Chemical Screening, Identification, and Comparison of Tripterygium Hypoglaucum Hutch Preparations by Ultra-High-Performance Liquid Chromatography-Quadrupole Time-of-Flight Mass Spectrometry Combined with Multivariate Statistical Analysis. J. Sep. Sci., 47.","DOI":"10.1002\/jssc.70023"},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Zhao, J.Q., Zhang, F.L., Xiao, X.L., Wu, Z., Hu, Q.C., Jiang, Y.X., Zhang, W.W., Wei, S.Z., Ma, X., and Zhang, X.M. (2021). Tripterygium hypoglaucum (L\u00e9vl.) Hutch and Its Main Bioactive Components: Recent Advances in Pharmacological Activity, Pharmacokinetics and Potential Toxicity. Front. Pharmacol., 12.","DOI":"10.3389\/fphar.2021.715359"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"326","DOI":"10.1039\/D2CC06073F","article-title":"Steroidal alkaloid with unprecedented triheterocyclic architecture","volume":"59","author":"Zhou","year":"2023","journal-title":"Chem. Commun."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1016\/S0031-9422(97)00288-4","article-title":"Di- and triterpenoids from Tripterygium hypoglaucum","volume":"46","author":"Duan","year":"1997","journal-title":"Phytochemistry"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"791","DOI":"10.1016\/S0031-9422(97)00048-4","article-title":"Terpenoids from Tripterygium wilfordii","volume":"45","author":"Li","year":"1997","journal-title":"Phytochemistry"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"473","DOI":"10.1016\/j.sajb.2005.12.011","article-title":"Antibacterial activity of maytenonic acid isolated from the root-bark of Maytenus senegalensis","volume":"72","author":"Lindsey","year":"2006","journal-title":"S. Afr. J. Bot."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"16529","DOI":"10.1073\/pnas.1904700116","article-title":"A selective membrane-targeting repurposed antibiotic with activity against persistent methicillin-resistant Staphylococcus aureus","volume":"116","author":"Kim","year":"2019","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Yuan, Z.W., Wang, J., Qu, Q.W., Zhu, Z.X., Xu, M.R., Zhao, M.M., Sun, C.X., Peng, H.X., Huang, X.Y., and Dong, Y. (2023). Celastrol Combats Methicillin-Resistant Staphylococcus aureus by Targeting \u03941-Pyrroline-5-Carboxylate Dehydrogenase. Adv. Sci., 10.","DOI":"10.1002\/advs.202302459"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"11522","DOI":"10.1039\/D0DT01665A","article-title":"Ciprofloxacin conjugated to diphenyltin(iv): A novel formulation with enhanced antimicrobial activity","volume":"49","author":"Chrysouli","year":"2020","journal-title":"Dalton Trans."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"884","DOI":"10.1021\/acsinfecdis.0c00913","article-title":"A Marine Antibiotic Kills Multidrug-Resistant Bacteria without Detectable High-Level Resistance","volume":"7","author":"Chen","year":"2021","journal-title":"ACS Infect. Dis."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Vinodhini, V., and Kavitha, M. (2024). Deciphering agr quorum sensing in Staphylococcus aureus: Insights and therapeutic prospects. Mol. Biol. Rep., 51.","DOI":"10.1007\/s11033-023-08930-3"},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Wang, X.H., Qiu, H.D., Yang, N., Xie, H.J., Liang, W.D., Lin, J.Y., Zhu, H.F., Zhou, Y., Wang, N., and Tan, X.Y. (2022). Fascaplysin derivatives binding to DNA via unique cationic five-ring coplanar backbone showed potent antimicrobial\/antibiofilm activity against MRSA in vitro and in vivo. Eur. J. Med. Chem., 230.","DOI":"10.1016\/j.ejmech.2021.114099"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1016\/j.ijbiomac.2021.08.199","article-title":"Focused review on dual inhibition of quorum sensing and efflux pumps: A potential way to combat multi drug resistant Staphylococcus aureus infections","volume":"190","author":"Kaur","year":"2021","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1174","DOI":"10.1016\/j.apsb.2019.05.002","article-title":"Hypericin enhances \u03b2-lactam antibiotics activity by inhibiting sarA expression in methicillin-resistant Staphylococcus aureus","volume":"9","author":"Wang","year":"2019","journal-title":"Acta Pharm. Sin. B"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1016\/j.foodcont.2018.08.020","article-title":"Antibiofilm activity of shikimic acid against Staphylococcus aureus","volume":"95","author":"Bai","year":"2019","journal-title":"Food Control"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"3938","DOI":"10.1039\/C8RA09136F","article-title":"Insight into the effect of quinic acid on biofilm formed by Staphylococcus aureus","volume":"9","author":"Bai","year":"2019","journal-title":"RSC Adv."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"667","DOI":"10.1038\/nrmicro3110","article-title":"Phenol-soluble modulins and staphylococcal infection","volume":"11","author":"Peschel","year":"2013","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Tomlinson, B.R., Malof, M.E., and Shaw, L.N. (2021). A global transcriptomic analysis of Staphylococcus aureus biofilm formation across diverse clonal lineages. Microb. Genomics, 7.","DOI":"10.1099\/mgen.0.000598"},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Gowrishankar, S., Kamaladevi, A., Balamurugan, K., and Pandian, S.K. (2016). In Vitro and In Vivo Biofilm Characterization of Methicillin-Resistant Staphylococcus aureus from Patients Associated with Pharyngitis Infection. Biomed. Res. Int., 2016.","DOI":"10.1155\/2016\/1289157"},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Wu, X.Y., Ma, G.L., Chen, H.W., Zhao, Z.Y., Zhu, Z.P., Xiong, J., Yang, G.X., and Hu, J.F. (2023). Antibacterial and antibiofilm efficacy of the preferred fractions and compounds from Euphorbia humifusa (herba euphorbiae humifusae) against Staphylococcus aureus. J. Ethnopharmacol., 306.","DOI":"10.1016\/j.jep.2023.116177"},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Kong, C., Chee, C.F., Richter, K., Thomas, N., Abd Rahman, N., and Nathan, S. (2018). Suppression of Staphylococcus aureus biofilm formation and virulence by a benzimidazole derivative, UM-C162. Sci. Rep., 8.","DOI":"10.1038\/s41598-018-21141-2"},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Qin, N., Tan, X.J., Jiao, Y.M., Liu, L., Zhao, W.S., Yang, S., and Jia, A.Q. (2014). RNA-Seq-based transcriptome analysis of methicillin-resistant Staphylococcus aureus biofilm inhibition by ursolic acid and resveratrol. Sci. Rep., 4.","DOI":"10.1038\/srep05467"},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Shi, C., Liu, X.F., Chen, Y.Y., Dai, J.M., Li, C.Z., Felemban, S., Khowdiary, M.M., Cui, H.Y., and Lin, L. (2024). Inhibitory effects of citral on the production of virulence factors in Staphylococcus aureus and its potential application in meat preservation. Int. J. Food Microbiol., 413.","DOI":"10.1016\/j.ijfoodmicro.2024.110581"},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Fedorowicz, J., Cruz, C.D., Morawska, M., Ciura, K., Gilbert-Girard, S., Mazur, L., Makkyla, H., Ilina, P., Savijoki, K., and Fallarero, A. (2023). Antibacterial and antibiofilm activity of permanently ionized quaternary ammonium fluoroquinolones. Eur. J. Med. Chem., 254.","DOI":"10.1016\/j.ejmech.2023.115373"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"8656","DOI":"10.1021\/acs.chemmater.1c02392","article-title":"Highly Efficient Biofilm Eradication by Antibacterial Two-Dimensional Supramolecular Polymers","volume":"33","author":"Mukherjee","year":"2021","journal-title":"Chem. Mat."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1840","DOI":"10.1111\/jam.15360","article-title":"Elucidating the antibiofilm activity of Frangula emodin against Staphylococcus aureus biofilms","volume":"132","author":"Tenji","year":"2022","journal-title":"J. Appl. Microbiol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"2322","DOI":"10.1021\/acs.jafc.2c08293","article-title":"New Efforts toward Aminothiazolylquinolones with Multitargeting Antibacterial Potential","volume":"71","author":"Zhang","year":"2023","journal-title":"J. Agric. Food Chem."},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Lee, E.H., Jeon, Y.H., An, S.J., Deng, Y.H., Kwon, H.B., Lim, Y.J., Kong, H., and Kim, M.J. (2022). Removal effect of Candida albicans biofilms from the PMMA resin surface by using a manganese oxide nanozyme-doped diatom microbubbler. Heliyon, 8.","DOI":"10.1016\/j.heliyon.2022.e12290"},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Li, J.Q., Yu, Y., Zhou, Y., Song, J.F., Yang, A.M., Wang, M., Li, Y.Z., Wan, M.Y., Zhang, C.H., and Yang, H. (2024). Multi-targeting oligopyridiniums: Rational design for biofilm dispersion and bacterial persister eradication. Bioorg. Chem., 144.","DOI":"10.1016\/j.bioorg.2024.107163"},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Cheng, F., Mo, Y.A., Chen, K.Y., Shang, X.Y., Yang, Z., Hao, B.C., Shang, R.F., Liang, J.P., and Liu, Y. (2021). Integration of metabolomics and transcriptomics indicates changes in MRSA exposed to terpinen-4-ol. BMC Microbiol., 21.","DOI":"10.1186\/s12866-021-02348-2"},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"He, R.R., Zhong, Q.P., Chen, W.J., Zhang, M., Pei, J.F., Chen, H.M., and Chen, W.X. (2023). Transcriptomic and proteomic investigation of metabolic disruption in Listeria monocytogenes triggered by linalool and its application in chicken breast preservation. LWT-Food Sci. Technol., 176.","DOI":"10.1016\/j.lwt.2023.114492"},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Putnam, C.D. (2021). Strand discrimination in DNA mismatch repair. DNA Repair, 105.","DOI":"10.1016\/j.dnarep.2021.103161"},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Yang, S., Li, J.Q., Aweya, J.J., Yuan, Z.J., Weng, W.Y., Zhang, Y.L., and Liu, G.M. (2020). Antimicrobial mechanism of Larimichthys crocea whey acidic protein-derived peptide (LCWAP) against Staphylococcus aureus and its application in milk. Int. J. Food Microbiol., 335.","DOI":"10.1016\/j.ijfoodmicro.2020.108891"},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Xie, Y.P., Ansari, M.F., Zhang, S.L., and Zhou, C.H. (2021). Novel carbazole-oxadiazoles as potential Staphylococcus aureus germicides. Pest. Biochem. Physiol., 175.","DOI":"10.1016\/j.pestbp.2021.104849"},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Wei, M.Z., Zhu, Y.Y., Zu, W.B., Wang, H., Bai, L.Y., Zhou, Z.S., Zhao, Y.L., Wang, Z.J., and Luo, X.D. (2024). Structure optimizing of flavonoids against both MRSA and VRE. Eur. J. Med. Chem., 271.","DOI":"10.1016\/j.ejmech.2024.116401"},{"key":"ref_57","doi-asserted-by":"crossref","unstructured":"Wei, M.Z., Wang, Z.J., Zhu, Y.Y., Zu, W.B., Zhao, Y.L., and Luo, X.D. (2024). Oleanolic acid derivatives against drug-resistant bacteria and fungi by multi-targets to avoid drug resistance. Eur. J. Med. Chem., 280.","DOI":"10.1016\/j.ejmech.2024.116940"},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"Yehia, F.A.A., Yousef, N., and Askoura, M. (2022). Celastrol mitigates staphyloxanthin biosynthesis and biofilm formation in Staphylococcus aureus via targeting key regulators of virulence; in vitro and in vivo approach. BMC Microbiol., 22.","DOI":"10.1186\/s12866-022-02515-z"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"576","DOI":"10.1016\/j.ejmech.2019.06.071","article-title":"Synthesis and biological evaluation of hybrid quinolone-based quaternary ammonium antibacterial agents","volume":"179","author":"Fedorowicz","year":"2019","journal-title":"Eur. J. Med. Chem."}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/30\/12\/2539\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T17:49:31Z","timestamp":1760032171000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/30\/12\/2539"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,6,10]]},"references-count":59,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2025,6]]}},"alternative-id":["molecules30122539"],"URL":"https:\/\/doi.org\/10.3390\/molecules30122539","relation":{},"ISSN":["1420-3049"],"issn-type":[{"value":"1420-3049","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,6,10]]}}}