{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T09:51:38Z","timestamp":1791021098621,"version":"4.1.0"},"reference-count":54,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2025,7,1]],"date-time":"2025-07-01T00:00:00Z","timestamp":1751328000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"the Fund for Scientific Research of the Plovdiv University","award":["C\u041f 23-X\u03a6-006"],"award-info":[{"award-number":["C\u041f 23-X\u03a6-006"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["BioTech"],"abstract":"<jats:p>This study investigates the cytotoxic properties of metal complexes incorporating thio-uracil derivatives, specifically 2,4-dithiouracil and 6-propyl-2-thiouracil. The research focuses on the cytotoxic effects of Cu(II) and Pd(II) complexes with 6-propyl-2-thiouracil, as well as mixed-ligand transition metal Cu(II) and Au(III) complexes of 2,4-dithiouracil with 2-thiouracil and uracil. Cytotoxic activity was assessed against human cervical carcinoma cells (HeLa) and normal kidney cells from the African green monkey. The results demonstrated that incorporating Cu(II) and Au(III) into the compound structures significantly enhanced their cytotoxic effects. Notably, all tested complexes exhibited a stronger inhibitory effect on cancer cell proliferation compared to normal cells, with the palladium(II) complex of 6-propyl-2-thiouracil showing the lowest CD50 value against the tumor cell line (0.00064 mM), which were 149 times lower than that of the ligand (0.0955 mM). These findings suggest that thio-uracil-based metal complexes, particularly those containing palladium (II) and gold(III), hold significant potential for further development as anticancer agents.<\/jats:p>","DOI":"10.3390\/biotech14030053","type":"journal-article","created":{"date-parts":[[2025,7,1]],"date-time":"2025-07-01T04:04:22Z","timestamp":1751342662000},"page":"53","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Investigation of the Cytotoxicity of Cu(II), Au(III), and Pd(II) Complexes with 2,4-Dithiouracil and 6-Propyl-2-thiouracil Derivatives"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2382-3291","authenticated-orcid":false,"given":"Petya","family":"Marinova","sequence":"first","affiliation":[{"name":"Department of General and Inorganic Chemistry with Methodology of Chemistry Education, Faculty of Chemistry, University of Plovdiv, \u201cTzar Assen\u201d str. 24, 4000 Plovdiv, Bulgaria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4939-881X","authenticated-orcid":false,"given":"Denica","family":"Blazheva","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Biotechnology, University of Food Technologies, 26 Maritza Blvd., 4002 Plovdiv, Bulgaria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aleksandar","family":"Slavchev","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Biotechnology, University of Food Technologies, 26 Maritza Blvd., 4002 Plovdiv, Bulgaria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Petia","family":"Genova-Kalou","sequence":"additional","affiliation":[{"name":"National Reference Laboratory \u201cRickettsia and Cell Cultures\u201d, Department of Virology, National Centre of Infectious and Parasitic Diseases, 1504 Sofia, Bulgaria"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,7,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"4373","DOI":"10.1007\/s11164-015-2281-1","article-title":"One-pot synthesis and in vivo biological evaluation of new pyrimidine privileged scaffolds as potent anti-inflammatory agents","volume":"42","author":"Undare","year":"2016","journal-title":"Res. Chem. Intermed."},{"key":"ref_2","first-page":"71","article-title":"Pyrimidine as a naturally occurring bioactive ring and its importance in different arenas","volume":"68","author":"Mohamed","year":"2025","journal-title":"Egypt. J. Chem."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Shi, W.-X., Lv, J.-Y., Xiao, W.-J., Xie, H.-D., Li, J.-J., Jiang, Y.-L., Su, X.-C., Xue, J.-Y., Li, C.-X., and Zou, Y. (2025). Pyrimidines to Pyridines: Two Atom Swap Skeletal Editing. CCS Chem., ahead of print.","DOI":"10.31635\/ccschem.025.202405166"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"11098","DOI":"10.1039\/D4RA00902A","article-title":"Synthesis of novel bioactive pyrido[2,3-d]pyrimidine derivatives with potent cytotoxicity through apoptosis as PIM-1 kinase inhibitors","volume":"14","author":"Tantawya","year":"2024","journal-title":"RSC Adv."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"e202500165","DOI":"10.1002\/ajoc.202500165","article-title":"Synthesis of Pyrimidines and Quinazolines via Acceptorless Dehydrogenative Coupling Catalyzed by PNN-Pd Complex","volume":"14","author":"Mohite","year":"2025","journal-title":"Asian J. Org. Chem."},{"key":"ref_6","first-page":"1","article-title":"Green Synthesis, Characterization and Biological Evaluation of Divalent Transition Metal Complexes of Substituted Aminopyrimidine Novel Schiff Base Ligand","volume":"13","author":"Sakhare","year":"2025","journal-title":"Sci. J. Chem."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1002\/jhet.4895","article-title":"Design, Synthesis of Novel Pyrimidine Derivatives Containing Alkenyl Moieties With Herbicidal Activities","volume":"62","author":"Zhang","year":"2025","journal-title":"J. Heterocycl. Chem."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"783","DOI":"10.1021\/acschemneuro.3c00662","article-title":"Novel Substituted Pyrimidine Derivatives as Potential Anti-Alzheimer\u2019s Agents: Synthesis, Biological, and Molecular Docking Studies","volume":"15","author":"Pant","year":"2024","journal-title":"ACS Chem. Neurosci."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"102008","DOI":"10.1016\/j.rechem.2024.102008","article-title":"Novel thiazolyl-pyrimidine derivatives as potential anticancer agents: Synthesis, biological evaluation, and molecular docking studies","volume":"13","author":"Abolibda","year":"2025","journal-title":"Results Chem."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1002\/jhet.4945","article-title":"Design, Synthesis, Antiproliferative Screening, and In Silico Studies of Some Pyridinyl-Pyrimidine Candidates","volume":"62","author":"Abdelrahman","year":"2025","journal-title":"J. Heterocycl. Chem."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1134\/S1070363217010182","article-title":"Complexes of Palladium(II) and Platinum(II) with 6-tert-Butyl-2-thiouracil","volume":"87","author":"Golubyatnikova","year":"2017","journal-title":"Russ. J. Gen. Chem."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"2452","DOI":"10.1016\/j.ica.2010.03.079","article-title":"Synthesis, characterization and in vitro cytotoxicity studies of platinum(IV) complexes with thiouracil ligands","volume":"363","author":"Vetter","year":"2010","journal-title":"Inorg. Chim. Acta"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1021\/acsomega.9b01921","article-title":"Nucleobase Derivatives as Building Blocks to Form Ru(II)-BasedComplexes with High Cytotoxicity","volume":"5","author":"Carvalho","year":"2020","journal-title":"ACS Omega"},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Correa, R.S., Bomfim, L.M., Oliveira, K.M., Moreira, D.R.M., Soares, M.B.P., Ellena, J., Bezerra, D.P., and Batista, A.A. (2019). Ru(II) complexes containing uracil nucleobase analogs with cytotoxicity against tumor cells. J. Inorg. Biochem., 198.","DOI":"10.1016\/j.jinorgbio.2019.110751"},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Bomfim, L.M., de Araujo, F.A., Dias, R.B., Sales, C.B.S., Gurgel Rocha, C.A., Correa, R.S., Soares, M.B.P., Batista, A.A., and Bezerra, D.P. (2019). Ruthenium(II) complexes with 6-methyl-2-thiouracil selectively reduce cell proliferation, cause DNA double-strand break and trigger caspase-mediated apoptosis through JNK\/p38 pathways in human acute promyelocytic leukemia cells. Sci. Rep., 9.","DOI":"10.1038\/s41598-019-47914-x"},{"key":"ref_16","first-page":"386","article-title":"Coordination Possibility of Uracil and Applications of Some of Its Complexes: A Review","volume":"4","author":"Oladipo","year":"2013","journal-title":"Res. J. Pharm. Biol. Chem. Sci."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"282","DOI":"10.2174\/157018012799129918","article-title":"Metal Complexes of Uracil Derivatives with Cytotoxicity and Superoxide Scavenging Activity","volume":"9","author":"Prachayasittikul","year":"2012","journal-title":"Lett. Drug Des. Discov."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Al-Halbosy, A.T.F., Hamada, A.A., Faihan, A.S., Saleh, A.M., Yousef, T.A., Abou-Krisha, M.M., Alhalafi, M.H., and Al-Janabi, A.S.M. (2023). Thiourea Derivative Metal Complexes: Spectroscopic, Anti-Microbial Evaluation, ADMET, Toxicity, and Molecular Docking Studies. Inorganics, 11.","DOI":"10.2139\/ssrn.4539217"},{"key":"ref_19","first-page":"1603","article-title":"Organo-metallic compounds: Novel molecules in cancer therapy","volume":"13","author":"Palma","year":"2014","journal-title":"Biochem. Pharmacol. Open Access"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"815","DOI":"10.1021\/cr400135x","article-title":"Advances in copper complexes as anticancer agents","volume":"114","author":"Santini","year":"2014","journal-title":"Chem. Rev."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1944","DOI":"10.2174\/13895575113136660092","article-title":"Copper complexes of bioactive ligands with superoxide dismutase activity","volume":"13","author":"Khalid","year":"2013","journal-title":"Mini Rev. Med. Chem."},{"key":"ref_22","first-page":"34","article-title":"A novel Schiff base derived from the gabapentin drug and copper (II) complex: Synthesis, characterization, interaction with DNA\/protein and cytotoxic activity","volume":"162","author":"Chiniforoshan","year":"2015","journal-title":"J. Photochem. Photobiol. B"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"8786","DOI":"10.1039\/C5CS00132C","article-title":"Chemical biology of anticancer gold(III) and gold(I) complexes","volume":"44","author":"Zou","year":"2015","journal-title":"Chem. Soc. Rev."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1515","DOI":"10.4155\/fmc.14.87","article-title":"Gold(III) complexes in medicinal chemistry","volume":"6","author":"Deflon","year":"2014","journal-title":"Future Med. Chem."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"6669","DOI":"10.1021\/om500965k","article-title":"Organometallic titanocene-gold compounds as potential chemotherapeutics in renal cancer. Study of their protein kinase inhibitory properties","volume":"33","author":"Ferna","year":"2014","journal-title":"Organometallics"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"2544","DOI":"10.1021\/om500118x","article-title":"Novel gold(I)\u2013 and gold(III)\u2013N-heterocyclic carbene complexes: Synthesis and evaluation of their anticancer properties","volume":"33","author":"Rana","year":"2014","journal-title":"Organometallics"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1016\/j.saa.2012.05.017","article-title":"Elaborated studies for the ligitional behavior of thiouracil derivative towards Ni(II), Pd(II), Pt(IV), Cu(II) and UO22 2 ions","volume":"97","year":"2012","journal-title":"Spectrochim. Acta Part A Mol. Biomol. Spectrosc."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"230","DOI":"10.1016\/j.saa.2007.03.039","article-title":"Synthesis and characterization of some pyrimidine, purine, amino acid and mixed ligand complexes","volume":"69","author":"Masoud","year":"2008","journal-title":"Spectrochim. Acta Part A"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1016\/0162-0134(89)85006-8","article-title":"The effect of histidine on the structure and antitumoractivity of metal-5-halouracil complexes","volume":"37","author":"Singh","year":"1989","journal-title":"J. Inorg. Biochem."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"144","DOI":"10.1016\/j.ica.2014.07.031","article-title":"Synthesis, characterization and anticancer activity of new zinc(II), molybdate(II), palladium(II), silver(I), rhodium(III), ruthenium(II) and platinum(II) complexes of 5,6-diamino-4-hydroxy2-mercaptopyrimidine","volume":"423","author":"Butler","year":"2014","journal-title":"Inorg. Chim. Acta"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1915","DOI":"10.1039\/C9DT04423J","article-title":"New selective thiolate gold(I) complexes inhibit proliferation of different human cancer cells and induce apoptosis in primary cultures of mouse colon tumors","volume":"49","author":"Laguna","year":"2020","journal-title":"Dalton Trans."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1155\/MBD.1998.35","article-title":"Synthesis, characterization and antitumour activity of metal complexes of 5-carboxy-2-thiouraci","volume":"5","author":"Singh","year":"1998","journal-title":"Met.-Based Drugs"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"383","DOI":"10.1016\/j.ejmech.2014.03.052","article-title":"Copper(I) halide complexes of 5-carbethoxy-2-thiouracil: Synthesis, structure and in vitro cytotoxicity","volume":"78","author":"Papazoglou","year":"2014","journal-title":"Eur. J. Med. Chem."},{"key":"ref_34","unstructured":"Hoeschele, J.D., and Piscataway, N.J. (1980). Ethylenediamineplatinum(II) 2,4-Dioxopyrimidine Complexes. (4,207,416), U.S. Patent."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1637","DOI":"10.1016\/j.jinorgbio.2005.05.003","article-title":"Synthesis, characterization and antiproliferative behavior of tricarbonyl complexes of rhenium(I) with some 6-amino-5-nitrosouracil derivatives: Crystal structure of fac-[ReCl(CO)3(DANU-N5,O4)] (DANU = 6-amino-1,3-dimethyl-5-nitrosouracil)","volume":"99","year":"2005","journal-title":"J. Inorg. Biochem."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1578","DOI":"10.1134\/S1070363222080278","article-title":"New Cu(II), Pd(II) and Au(III) complexes with 2-thiouracil: Synthesis, Characteration and Antibacterial Studies","volume":"92","author":"Marinova","year":"2022","journal-title":"Russ. J. Gen. Chem."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Marinova, P., Hristov, M., Tsoneva, S., Burdzhiev, N., Blazheva, D., Slavchev, A., Varbanova, E., and Penchev, P. (2023). Synthesis, Characterization, and Antibacterial Studies of New Cu(II) and Pd(II) Complexes with 6-Methyl-2-Thiouracil and 6-Propyl-2-Thiouracil. Appl. Sci., 13.","DOI":"10.20944\/preprints202311.0437.v1"},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Marinova, P., Stoitsov, D., Burdzhiev, N., Tsoneva, S., Blazheva, D., Slavchev, A., Varbanova, E., and Penchev, P. (2024). Investigation of the Complexation Activity of 2,4-Dithiouracil with Au(III) and Cu(II) and Biological Activity of the Newly Formed Complexes. Appl. Sci., 14.","DOI":"10.3390\/app14156601"},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Marinova, P., Burdzhiev, N., Blazheva, D., and Slavchev, A. (2024). Synthesis and Antibacterial Studies of a New Au(III) Complex with 6-Methyl-2-Thioxo-2,3-Dihydropyrimidin-4(1H)-One. Molbank, 2024.","DOI":"10.3390\/M1827"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"186","DOI":"10.3390\/compounds4010010","article-title":"Synthesis and Biological Activities of Some Metal Complexes of 2-Thiouracil and Its Derivatives: A Review","volume":"4","author":"Marinova","year":"2024","journal-title":"Compounds"},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Adhikari, S., Nath, P., Das, A., Datta, A., Baildya, N., Duttaroy, A.K., and Pathak, S. (2024). A review on metal complexes and its anti-cancer activities: Recent updates from in vivo studies. Biomed. Pharmacother., 171.","DOI":"10.1016\/j.biopha.2024.116211"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"5518","DOI":"10.1039\/D1CS00933H","article-title":"Recent development of gold(I) and gold(III)complexes as therapeutic agents for cancer diseases","volume":"51","author":"Lu","year":"2022","journal-title":"Chem. Soc. Rev."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"7467","DOI":"10.1039\/D1SC01418H","article-title":"Anticancer gold(III)-bisphosphine complex alters the mitochondrial electron transport chain to induce in vivo tumor inhibition","volume":"12","author":"Kim","year":"2021","journal-title":"Chem. Sci."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"10237","DOI":"10.1039\/D2CC03081K","article-title":"Chiral gold(III) complexes: Speciation, in vitro, and in vivo anticancer profile","volume":"58","author":"Arojojoye","year":"2022","journal-title":"Chem. Commun."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"mfab039h","DOI":"10.1093\/mtomcs\/mfab039","article-title":"Dinuclear orthometallatedgold(I)-gold(III) anticancer complexes with potent in vivo activity through an ROS-dependent mechanism","volume":"13","author":"Mirzadeh","year":"2021","journal-title":"Metallomics"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"220","DOI":"10.1016\/j.ejmech.2018.05.023","article-title":"Two new Cu(II) dipeptide complexes based on 5-methyl-2-(2\u2019-pyridyl)benzimidazole as potential antimicrobial and anticancer drugs: Special exploration of their possible anticancer mechanism","volume":"154","author":"Qi","year":"2018","journal-title":"Eur. J. Med. Chem."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1016\/j.ejmech.2017.12.048","article-title":"Synthesis of gold(I) phosphine complexes containing the 2-BrC6F4PPh2 ligand: Evaluation of anticancer activity in 2D and 3D spheroidal models of HeLa cancer cells","volume":"145","author":"Reddy","year":"2018","journal-title":"Eur. J. Med. Chem."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1016\/j.ejmech.2019.05.030","article-title":"Optically pure chiral copper(II) complexes of rosin derivative as attractive anticancer agents with potential anti-metastatic and anti-angiogenic activities","volume":"176","author":"Fei","year":"2019","journal-title":"Eur. J. Med. Chem."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1016\/j.ejmech.2018.11.047","article-title":"In vitro and in vivo anti-tumor activity of two gold(III) complexes with isoquinoline derivatives as ligands","volume":"163","author":"Khan","year":"2019","journal-title":"Eur. J. Med. Chem."},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"P\u00e9rez-Villanueva, J., Matadamas-Mart\u00ednez, F., Y\u00e9pez-Mulia, L., P\u00e9rez-Koldenkova, V., Leyte-Lugo, M., Rodr\u00edguez-Villar, K., Cort\u00e9s-Ben\u00edtez, F., Mac\u00edas-Jim\u00e9nez, A.P., Gonz\u00e1lez-S\u00e1nchez, I., and Romero-Vel\u00e1squez, A. (2021). Synthesis and Cytotoxic Activity of Combretastatin A-4 and 2,3-Diphenyl-2H-indazole Hybrids. Pharmaceuticals, 14.","DOI":"10.3390\/ph14080815"},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Zeng, Z.-F., Huang, Q.-P., Cai, J.-H., Zheng, G.-J., Huang, Q.-C., Liu, Z.-L., Chen, Z.-L., and Wei, Y.-H. (2021). Synthesis, Characterization, DNA\/HSA Interactions, and Anticancer Activity of Two Novel Copper(II) Complexes with 4-Chloro-3-Nitrobenzoic Acid Ligand. Molecules, 26.","DOI":"10.3390\/molecules26134028"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"202","DOI":"10.26650\/IstanbulJPharm.2020.0039","article-title":"Interaction of curcumin on cisplatin cytotoxicity in HeLa and HepG2 carcinoma cells","volume":"50","author":"Becit","year":"2020","journal-title":"Istanb. J. Pharm."},{"key":"ref_53","first-page":"58","article-title":"Effect of HeLa Cell Density Towards Cisplatin Treatment","volume":"12","author":"Ganesan","year":"2022","journal-title":"Proc. Sci. Math."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"154","DOI":"10.1186\/s12935-019-0868-0","article-title":"Effect of Gallic acid in potentiating chemotherapeutic effect of Paclitaxel in HeLa cervical cancer cells","volume":"19","author":"Aborehab","year":"2019","journal-title":"Cancer Cell Int."}],"container-title":["BioTech"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2673-6284\/14\/3\/53\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T18:02:09Z","timestamp":1760032929000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2673-6284\/14\/3\/53"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,7,1]]},"references-count":54,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2025,9]]}},"alternative-id":["biotech14030053"],"URL":"https:\/\/doi.org\/10.3390\/biotech14030053","relation":{},"ISSN":["2673-6284"],"issn-type":[{"value":"2673-6284","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,7,1]]}}}