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Seville)","award":["100521265-VIEP2024"],"award-info":[{"award-number":["100521265-VIEP2024"]}]},{"name":"VIEP-BUAP","award":["PID2020-116460RB-I00"],"award-info":[{"award-number":["PID2020-116460RB-I00"]}]},{"name":"VIEP-BUAP","award":["PID2021-123059OB-I00"],"award-info":[{"award-number":["PID2021-123059OB-I00"]}]},{"name":"VIEP-BUAP","award":["FQM134"],"award-info":[{"award-number":["FQM134"]}]},{"name":"VIEP-BUAP","award":["100521265-VIEP2024"],"award-info":[{"award-number":["100521265-VIEP2024"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The selective inhibition of key enzymes, such as carbonic anhydrases (CAs IX and XII), which are overexpressed in cancer tissues, has emerged as a promising strategy in cancer research. However, a multitarget approach is often preferred to achieve enhanced therapeutic outcomes. In this study, aryl sulfonamides were conjugated with a thiosemicarbazone moiety to enable dual functionality: the inhibition of CAs and the chelation of metal cations. Several structural factors were systematically modified, including the position of the sulfonamido group, the length of the linker, the nature of the aromatic residue, and the type of substituents. Tumor-associated CAs IX and XII inhibition was evaluated using the stopped-flow CO2 hydrase assay, and the inhibition constants (Ki) were determined. The most promising compounds were further analyzed through molecular docking simulations. Metal chelation capabilities were evaluated using UV\u2013Vis spectroscopy, while antiproliferative activities were measured using the sulforhodamine B (SBR) assay. Additionally, holotomographic 3D microscopy was employed to investigate the mechanisms of cell death. Sulfonamido-derived Schiff bases were synthesized through a three-step procedure that did not require column chromatography purification: (1) isothiocyanation of amino-sulfonamides, (2) nucleophilic addition of hydrazine, and (3) acid-promoted condensation with different aldehydes (benzaldehydes or pyridine-2-carboxaldehyde). The synthesized compounds exhibited inhibition of CAs in the low nanomolar to submicromolar range, with selectivity largely influenced by structural features. Notably, the m-sulfonamide derivative 5b, bearing a pyridin-2-yl residue, demonstrated potent and selective inhibition of CA IX (Ki = 4.9 nM) and XII (Ki = 5.6 nM). Additionally, it efficiently chelated Fe2+, Fe3+, and Cu2+ and showed promising antiproliferative activity (GI50 4.5\u201310 \u00b5M). Mechanistic studies revealed that apoptosis was involved in its mode of action. Therefore, the synergistic integration of sulfonamides and thiosemicarbazones represents an effective strategy for the development of multimodal anticancer agents.<\/jats:p>","DOI":"10.3390\/ijms26031225","type":"journal-article","created":{"date-parts":[[2025,1,30]],"date-time":"2025-01-30T11:08:23Z","timestamp":1738235303000},"page":"1225","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Multifaceted Sulfonamide-Derived Thiosemicarbazones: Combining Metal Chelation and Carbonic Anhydrases Inhibition in Anticancer Therapy"],"prefix":"10.3390","volume":"26","author":[{"given":"M\u00f3nica","family":"Mart\u00ednez-Montiel","sequence":"first","affiliation":[{"name":"Departamento de Qu\u00edmica Org\u00e1nica, Facultad de Qu\u00edmica, Universidad de Sevilla, Apartado 1203, E-41071 Seville, Spain"},{"name":"Facultad de Ciencias Qu\u00edmicas, Ciudad Universitaria, Benem\u00e9rita Universidad Aut\u00f3noma de 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WHO (World Health Organization). Available online: https:\/\/www.who.int\/health-topics\/cancer#tab=tab_1."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s43018-019-0023-9","article-title":"The global challenge of cancer","volume":"1","author":"Nguyen","year":"2020","journal-title":"Nat. Cancer"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1016\/j.pbiomolbio.2022.09.009","article-title":"Cancer\u2014A devastating disease, but also an eye-opener and window into the deep mysteries of life and its origins","volume":"175","author":"Grunt","year":"2022","journal-title":"Progress Biophys. Mol. Biol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"eaay9040","DOI":"10.1126\/science.aay9040","article-title":"Early detection of cancer","volume":"375","author":"Crosby","year":"2022","journal-title":"Science"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1037","DOI":"10.21037\/jgo.2018.05.05","article-title":"Advances in surgery for pancreatic cancer","volume":"9","author":"Acher","year":"2018","journal-title":"J. Gastrointest. Oncol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"S7","DOI":"10.1038\/d41586-024-01428-3","article-title":"Advances in highly targeted radiation treatment for cancer have ignited interest in a once obscure field","volume":"629","author":"Nuwer","year":"2024","journal-title":"Nature"},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Liu, Q., Wu, P., Lei, J., Bai, P., Zhong, P., Yang, M., and Wei, P. (2025). Old concepts, new tricks: How peptide vaccines are reshaping cancer immunotherapy?. Int. J. Biol. Macromol., 279.","DOI":"10.1016\/j.ijbiomac.2024.135541"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"3881","DOI":"10.1039\/D3TB01066J","article-title":"Near-infrared-driven upconversion nanoparticles with photocatalysts through water-splitting towards cancer treatment","volume":"12","author":"Dash","year":"2024","journal-title":"J. Mater. Chem. B"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1367","DOI":"10.1016\/j.gendis.2022.02.007","article-title":"Cancer chemotherapy and beyond: Current status, drug candidates, associated risks and progress in targeted therapeutics","volume":"10","author":"Anand","year":"2023","journal-title":"Genes Dis."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"473","DOI":"10.1038\/nrc2394","article-title":"Paul Ehrlich\u2019s magic bullet concept: 100 years of progress","volume":"8","author":"Strebhardt","year":"2008","journal-title":"Nat. Rev. Cancer"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"106055","DOI":"10.1016\/j.phrs.2021.106055","article-title":"Polypharmacology: The science of multi-targeting molecules","volume":"176","author":"Kabir","year":"2022","journal-title":"Pharmacol. Res."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Liu, X.-J., Zhao, H.-C., Hou, S.-J., Zhang, H.-J., Cheng, L., Yuan, S., Zhang, L.-R., Song, J., Zhang, S.-Y., and Chen, S.-W. (2023). Recent development of multi-target VEGFR-2 inhibitors for the cancer therapy. Bioorg. Chem., 133.","DOI":"10.1016\/j.bioorg.2023.106425"},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Occhipinti, R., and Boron, W.F. (2019). Role of carbonic anhydrases and inhibitors in acid\u2013base physiology: Insights from mathematical modelling. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20153841"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"4557","DOI":"10.1038\/s41467-020-18425-5","article-title":"Elucidating the role of metal ions in carbonic anhydrase catalysis","volume":"11","author":"Kim","year":"2020","journal-title":"Nat. Commun."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"100004","DOI":"10.1124\/pharmrev.124.001125","article-title":"Multi- and poly-pharmacology of carbonic anhydrase inhibitors","volume":"77","author":"Supuran","year":"2025","journal-title":"Pharmacol. Rev"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"112923","DOI":"10.1016\/j.ejmech.2020.112923","article-title":"Recent advances in the medicinal chemistry of carbonic anhydrase inhibitors","volume":"209","author":"Kumar","year":"2021","journal-title":"Eur. J. Med. Chem."},{"key":"ref_17","first-page":"3","article-title":"Advances in anti-cancer drug development targeting carbonic anhydrase IX and XII","volume":"5","author":"Mboge","year":"2015","journal-title":"Top. Anticancer Res."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Higazy, S., Samir, N., El-Khouly, A., Giovannuzzi, S., Begines, P., Gaber, H.M., Supuran, C.T., and Abouzid, K.A.M. (2024). Identification of thienopyrimidine derivatives tethered with sulfonamide and other moieties as carbonic anhydrase inhibitors: Design, synthesis and anti-proliferative activity. Bioorg. Chem., 144.","DOI":"10.1016\/j.bioorg.2023.107089"},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Elsayad, K.A., Elmasry, G.F., Mahmoud, S.T., and Awadallah, F.M. (2024). Sulfonamides as anticancer agents: A brief review on sulfonamide derivatives as inhibitors of various proteins overexpressed in cancer. Bioorg. Chem., 147.","DOI":"10.1016\/j.bioorg.2024.107409"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1186\/s13046-022-02345-x","article-title":"Inhibition of carbonic anhydrases IX\/XII by SLC-0111 boosts cisplatin effects in hampering head and neck squamous carcinoma cell growth and invasion","volume":"41","author":"Sarnella","year":"2022","journal-title":"J. Exp. Clin. Cancer Res."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Eloranta, K., Pihlajoki, M., Liljestr\u00f6m, E., Nousiainen, R., Soini, T., Lohi, J., Cairo, S., Wilson, D.B., Parkkila, S., and Heikinheimo, M. (2023). SLC-0111, an inhibitor of carbonic anhydrase IX, attenuates hepatoblastoma cell viability and migration. Front. Oncol., 13.","DOI":"10.3389\/fonc.2023.1118268"},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Jomova, K., Makova, M., Alomar, S.Y., Alwasel, S.H., Nepovimova, E., Kuca, K., Rhodes, C.J., and Valko, M. (2022). Essential metals in health and disease. Chem.-Biol. Interact., 367.","DOI":"10.1016\/j.cbi.2022.110173"},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Krzywoszy\u0144ska, K., Witkowska, D., \u015awi\u0105tek-Koz\u0142owska, J., Szebesczyk, A., and Koz\u0142owski, H. (2020). General aspects of metal ions as signaling agents in health and disease. Biomolecules, 10.","DOI":"10.3390\/biom10101417"},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Serra, M., Columbano, A., Ammarah, U., Mazzone, M., and Menga, A. (2020). Understanding metal dynamics between cancer cells and macrophages: Competition or synergism?. Front. Oncol., 10.","DOI":"10.3389\/fonc.2020.00646"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"e202300624","DOI":"10.1002\/cplu.202300624","article-title":"Modulation of metal homeostasis for cancer therapy","volume":"89","author":"Yang","year":"2024","journal-title":"ChemPlusChem"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"180","DOI":"10.1016\/j.cca.2019.11.029","article-title":"Iron overload: Effects on cellular biochemistry","volume":"504","author":"Sousa","year":"2000","journal-title":"Clin. Chim. Acta"},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Guan, D., Zhao, L., Shi, X., Ma, X., and Chen, Z. (2023). Copper in cancer: From pathogenesis to therapy. Biomed. Pharmacother., 163.","DOI":"10.1016\/j.biopha.2023.114791"},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Kontoghiorghes, G.J. (2022). New iron metabolic pathways and chelation targeting strategies affecting the treatment of all types and stages of cancer. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms232213990"},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Hassan, A.E., Albohy, S.A.H., Elzaref, A.S., Elfeky, A.S., El-Fakharany, E.M., Saleh, A.K., Mahmoud, A.M., and Elgammal, W.E. (2024). Metal complexes with thiosemicarbazone derivative and isatine: A promising new class of materials for biomedical and environmental applications. J. Photochem. Photobiol. A Chem., 455.","DOI":"10.1016\/j.jphotochem.2024.115764"},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Aly, A.A., Abdallah, E.M., Ahmed, S.A., Rabee, M.M., and Br\u00e4se, S. (2023). Transition metal complexes of thiosemicarbazides, thiocarbohydrazides, and their corresponding carbazones with Cu(I), Cu(II), Co(II), Ni(II), Pd(II), and Ag(I)\u2014A review. Molecules, 28.","DOI":"10.3390\/molecules28041808"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"264","DOI":"10.1016\/j.ica.2017.07.001","article-title":"A comparative study of \u03b1-N-pyridyl thiosemicarbazones: Spectroscopic properties, solution stability and copper(II) complexation","volume":"472","author":"May","year":"2018","journal-title":"Inorg. Chim. Acta"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"116363","DOI":"10.1016\/j.ejmech.2024.116363","article-title":"Schiff bases and their metal complexes to target and overcome (multidrug) resistance in cancer","volume":"270","author":"Valente","year":"2024","journal-title":"Eur. J. Med. Chem."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"537","DOI":"10.13005\/ojc\/380303","article-title":"Synthesis, characterization, optical, DFT, TD DFT studies and in silico ADME predictions of thiosemicarbazone ligand and its Au(III) complex","volume":"38","author":"Yousef","year":"2022","journal-title":"Orient. J. Chem."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"127180","DOI":"10.1016\/j.molstruc.2019.127180","article-title":"Synthesis, and biological evaluation of complexes based on thiosemicarbazone ligand","volume":"1201","author":"Yousef","year":"2020","journal-title":"J. Mol. Struct."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1016\/j.ejmech.2019.03.024","article-title":"Multi-target compounds acting in cancer progression: Focus on thiosemicarbazone, thiazole and thiazolidinone analogues","volume":"170","author":"Leite","year":"2019","journal-title":"Eur. J. Med. Chem."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"638","DOI":"10.2174\/1389557519666191029130310","article-title":"Thiosemicarbazones as potent anticancer agents and their modes of action","volume":"20","author":"Shakya","year":"2020","journal-title":"Mini-Rev. Med. Chem."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"13023","DOI":"10.3390\/ijms160613023","article-title":"Synthesis, DNA binding, and antiproliferative activity of novel acridine-thiosemicarbazone derivatives","volume":"16","year":"2015","journal-title":"Int. J. Mol. Sci."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1538","DOI":"10.1016\/j.biopha.2017.11.054","article-title":"DNA binding and topoisomerase inhibition: How can these mechanisms be explored to design more specific anticancer agents?","volume":"96","author":"Ribeiro","year":"2017","journal-title":"Biomed. Pharmacother."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1143","DOI":"10.4155\/fmc.09.80","article-title":"Thiosemicarbazones: The new wave in cancer treatment","volume":"1","author":"Kalinowski","year":"2009","journal-title":"Fut. Med. Chem."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"mfad046","DOI":"10.1093\/mtomcs\/mfad046","article-title":"Human serum albumin as a copper source for anticancer thiosemicarbazones","volume":"15","author":"Schaier","year":"2023","journal-title":"Metallomics"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1062","DOI":"10.1089\/ars.2017.7487","article-title":"Anticancer thiosemicarbazones: Chemical properties, interaction with iron metabolism, and resistance development","volume":"30","author":"Heffeter","year":"2019","journal-title":"Antioxid. Redox Signal."},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Ohui, K., Stepanenko, I., Besleaga, I., Babak, M.V., Stafi, R., Darvasiova, D., Giester, G., P\u00f3sa, V., Enyedy, E.A., and Vegh, D. (2010). Triapine derivatives act as copper delivery vehicles to induce deadly metal overload in cancer cells. Biomolecules, 10.","DOI":"10.3390\/biom10091336"},{"key":"ref_43","first-page":"684","article-title":"Synthesis of certain new thiazole derivatives bearing a sulfonamide moiety with expected anticancer and radiosensitizing activities","volume":"1","author":"Ghorab","year":"2011","journal-title":"J. Mat. Sci. Eng. A"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.bbrc.2004.03.181","article-title":"Potent isothiocyanate inhibitors of carbonic anhydrase: Synthesis and evaluation","volume":"318","author":"Khobzaoui","year":"2004","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"2598","DOI":"10.1158\/1535-7163.MCT-18-0533","article-title":"Carbonic anhydrase XII inhibitors overcome P-glycoprotein-mediated resistance to temozolomide in glioblastoma","volume":"17","author":"Salaroglio","year":"2018","journal-title":"Mol. Cancer Ther."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"781","DOI":"10.1080\/13543776.2019.1679117","article-title":"Carbonic anhydrase inhibition and the management of glaucoma: A literature and patent review 2013\u20132019","volume":"29","author":"Supuran","year":"2019","journal-title":"Expert Opin. Ther. Pat."},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Mart\u00ednez-Montiel, M., Romero-Hern\u00e1ndez, L.L., Giovannuzzi, S., Begines, P., Puerta, A., Ahuja-Casar\u00edn, A.I., Fernandes, M.X., Merino-Montiel, P., Montiel-Smith, S., and Nocentini, A. (2023). Conformationally restricted glycoconjugates derived from arylsulfonamides and coumarins: New families of tumour-associated carbonic anhydrase inhibitors. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24119401"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"224","DOI":"10.1021\/acs.inorgchem.2c03259","article-title":"Coordination chemistry of potentially S,N,Npy-tridentate thiosemicarbazones with the {Re(CO)3}+ fragment and formation of hemiaminal derivatives","volume":"62","author":"Carballo","year":"2023","journal-title":"Inorg. Chem."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"442","DOI":"10.1016\/j.ejmech.2018.09.020","article-title":"Designing anticancer copper(II) complexes by optimizing 2-pyridine-thiosemicarbazone ligands","volume":"158","author":"Deng","year":"2018","journal-title":"Eur. J. Med. Chem."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1018951","DOI":"10.3389\/fphar.2022.1018951","article-title":"Advances in thiosemicarbazone metal complexes as anti-lung cancer agents","volume":"13","author":"Bai","year":"2022","journal-title":"Front. Pharmacol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"112349","DOI":"10.1016\/j.ejmech.2020.112349","article-title":"Thiosemicarbazone-based lead optimization to discover high-efficiency and low-toxicity anti-gastric cancer agents","volume":"199","author":"Zhang","year":"2020","journal-title":"Eur. J. Med. Chem."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1016\/j.ejmech.2016.03.078","article-title":"Design, synthesis and biological evaluation of thiosemicarbazones, hydrazinobenzothiazoles and arylhydrazones as anticancer agents with a potential to overcome multidrug resistance","volume":"117","author":"Pape","year":"2016","journal-title":"Eur. J. Med. Chem."},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Rold\u00e1n-Pe\u00f1a, J.M., Puerta, A., Dini\u0107, J., Jovanovi\u0107 Stojanov, S., Gonz\u00e1lez-Bakker, A., Hicke, F.J., Mishra, A., Piyasaengthong, A., Maya, I., and Walton, J.W. (2023). Biotinylated selenocyanates: Potent and selective cytostatic agents. Bioorg. Chem., 133.","DOI":"10.1016\/j.bioorg.2023.106410"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"115390","DOI":"10.1016\/j.ejmech.2023.115390","article-title":"Fluoro-labelled sp2-iminoglycolipids with immunomodulatory properties","volume":"255","author":"Puerta","year":"2023","journal-title":"Eur. J. Med. Chem."},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Puerta, A., Gonz\u00e1lez-Bakker, A., Santos, G., and Padr\u00f3n, J.M. (2022). Early pharmacological profiling of antiproliferative compounds by live cell Imaging. Molecules, 27.","DOI":"10.3390\/molecules27165261"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"2176","DOI":"10.1021\/om100106e","article-title":"NMR Chemical shifts of traceimpurities: Common laboratory solvents, organics, and gases in deuterated solvents relevant to the organometallic chemist","volume":"29","author":"Fulmer","year":"2010","journal-title":"Organometallics"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"3714","DOI":"10.1016\/j.bmc.2017.05.029","article-title":"Novel sulfonamide-containing 2-indolinones that selectively inhibit tumor-associated alpha carbonic anhydrases","volume":"25","author":"Akdemir","year":"2017","journal-title":"Bioorg. Med. Chem."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"2133","DOI":"10.4155\/fmc-2021-0018","article-title":"Synthesis, molecular modeling and cholinesterase inhibitory effects of 2-indolinone-based hydrazinecarbothioamides","volume":"13","author":"Apaydin","year":"2021","journal-title":"Fut. Med. Chem."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"649","DOI":"10.2174\/0118715206290722240125112447","article-title":"Thiosemicarbazone-benzenesulfonamide derivatives as human carbonic anhydrases inhibitors: Synthesis, characterization, and in silico studies","volume":"24","author":"Trawally","year":"2024","journal-title":"Anti-Cancer Agents Med. Chem."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1093\/nar\/28.1.235","article-title":"The Protein Data Bank","volume":"28","author":"Berman","year":"2000","journal-title":"Nucleic Acids Res."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/3\/1225\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T16:24:25Z","timestamp":1760027065000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/3\/1225"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,1,30]]},"references-count":60,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2025,2]]}},"alternative-id":["ijms26031225"],"URL":"https:\/\/doi.org\/10.3390\/ijms26031225","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,1,30]]}}}