{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T17:59:16Z","timestamp":1784743156774,"version":"3.55.0"},"reference-count":50,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2025,1,20]],"date-time":"2025-01-20T00:00:00Z","timestamp":1737331200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The present study aims to create spiro-N-(4-sulfamoyl-phenyl)-1,3,4-thiadiazole-2-carboxamide derivatives with anticancer activities. The in vitro anticancer evaluation showed that only the novel spiro-acenaphthylene tethered-[1,3,4]-thiadiazole (compound 1) exhibited significant anticancer efficacy as a selective inhibitor of tumor-associated isoforms of carbonic anhydrase. Compound 1 demonstrated considerable efficacy against the renal RXF393, colon HT29, and melanoma LOX IMVI cancer cell lines, with IC50 values of 7.01 \u00b1 0.39, 24.3 \u00b1 1.29, and 9.55 \u00b1 0.51 \u00b5M, respectively. In comparison, doxorubicin exhibited IC50 values of 13.54 \u00b1 0.82, 13.50 \u00b1 0.71, and 6.08 \u00b1 0.32 \u00b5M for the corresponding cell lines. Importantly, compound 1 exhibited lower toxicity to the normal WI 38 cell line than doxorubicin, with IC50 values of 46.20 \u00b1 2.59 and 18.13 \u00b1 0.93 \u00b5M, respectively, indicating greater selectivity of the target compound compared to the standard anticancer agent doxorubicin. Also, mechanistic experiments demonstrated that compound 1 exhibits inhibitory activity against human carbonic anhydrase hCA IX and XII, with IC50 values of 0.477 \u00b1 0.03 and 1.933 \u00b1 0.11 \u03bcM, respectively, indicating enhanced selectivity for cancer-associated isoforms over cytosolic isoforms hCA I and II, with IC50 values of 7.353 \u00b1 0.36 and 12.560 \u00b1 0.74 \u03bcM, respectively. Cell cycle studies revealed that compound 1 caused G1 phase arrest in RXF393 cells, and apoptosis experiments verified a substantial induction of apoptosis with significant levels of early and late apoptosis, as well as necrosis (11.69%, 19.78%, and 3.66%, respectively), comparable to those induced by the conventional cytotoxic agent doxorubicin, at 9.91%, 23.37%, and 6.16%, respectively. Molecular docking experiments confirmed the strong binding affinity of compound 1 to the active sites of hCA IX and XII, highlighting significant interactions with zinc-binding groups and hydrophobic residues. These findings underscore the target compound\u2019s potential as a viable anticancer agent via targeting CA.<\/jats:p>","DOI":"10.3390\/ijms26020863","type":"journal-article","created":{"date-parts":[[2025,1,21]],"date-time":"2025-01-21T06:53:32Z","timestamp":1737442412000},"page":"863","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Design, Synthesis, Anticancer Screening, and Mechanistic Study of Spiro-N-(4-sulfamoyl-phenyl)-1,3,4-thiadiazole-2-carboxamide Derivatives"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4338-1486","authenticated-orcid":false,"given":"Ahmed M.","family":"El-Saghier","sequence":"first","affiliation":[{"name":"Department of Chemistry, Faculty of Science, Sohag University, Sohag 82524, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8649-7534","authenticated-orcid":false,"given":"Hamada","family":"Hashem","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Sohag University, Sohag 82524, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sherif A.","family":"Maher","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Faculty of Pharmacy, New Valley University, New Valley 72511, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-4254-7137","authenticated-orcid":false,"given":"Souhaila S.","family":"Enaili","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Faculty of Science, University of Zawia, Az Zawiyah 16418, Libya"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-2000-2620","authenticated-orcid":false,"given":"Abdullah","family":"Alkhammash","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, College of Pharmacy, Shaqra University, Shaqra 11961, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4845-3191","authenticated-orcid":false,"given":"Stefan","family":"Br\u00e4se","sequence":"additional","affiliation":[{"name":"Institute for Biological and Chemical System, Karlsruhe Institute of Technology, 76131 Karlsruhe, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hossameldin A.","family":"Aziz","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry, Faculty of Pharmacy, New Valley University, New Valley 72511, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,1,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"69","DOI":"10.3322\/caac.20107","article-title":"Global cancer statistics","volume":"61","author":"Jemal","year":"2011","journal-title":"CA Cancer J. Clin."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Aziz, H.A., El-Saghier, A.M., Badr, M., Elsadek, B.E., Abuo-Rahma, G.E., and Shoman, M.E. (2024). Design, synthesis and mechanistic study of N-4-Piperazinyl Butyryl Thiazolidinedione derivatives of ciprofloxacin with Anticancer Activity via Topoisomerase I\/II inhibition. Sci. Rep., 14.","DOI":"10.1038\/s41598-024-73793-y"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1346","DOI":"10.1080\/14756366.2022.2072308","article-title":"New 1,2,3-triazole linked ciprofloxacin-chalcones induce DNA damage by inhibiting human topoisomerase I& II and tubulin polymerization","volume":"37","author":"Mohammed","year":"2022","journal-title":"J. Enzym. Inhib. Med. Chem."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"172","DOI":"10.1016\/j.semcancer.2022.12.011","article-title":"Tumor hypoxia: From basic knowledge to therapeutic implications","volume":"88","author":"Liao","year":"2023","journal-title":"Semin. Cancer Biol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1038\/s41392-023-01332-8","article-title":"Hypoxic microenvironment in cancer: Molecular mechanisms and therapeutic interventions","volume":"8","author":"Chen","year":"2023","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1016\/j.semcancer.2021.10.002","article-title":"Hypoxia signaling: Challenges and opportunities for cancer therapy","volume":"85","author":"Ivan","year":"2022","journal-title":"Semin. Cancer Biol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1216","DOI":"10.1016\/j.semcancer.2022.09.007","article-title":"Tumor glycolysis, an essential sweet tooth of tumor cells","volume":"86","author":"Paul","year":"2022","journal-title":"Semin. Cancer Biol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"4642","DOI":"10.1021\/acs.biochem.6b00243","article-title":"The structure of carbonic anhydrase IX is adapted for low-pH catalysis","volume":"55","author":"Mahon","year":"2016","journal-title":"Biochemistry"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1038\/s41416-019-0642-z","article-title":"Carbonic anhydrase IX and acid transport in cancer","volume":"122","author":"Becker","year":"2020","journal-title":"Br. J. Cancer"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"899","DOI":"10.1016\/j.semcancer.2022.01.001","article-title":"Carbonic anhydrase IX: A tumor acidification switch in heterogeneity and chemokine regulation","volume":"86","author":"Queen","year":"2022","journal-title":"Semin. Cancer Biol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1278","DOI":"10.1080\/14756366.2022.2052868","article-title":"Targeting carbonic anhydrase IX and XII isoforms with small molecule inhibitors and monoclonal antibodies","volume":"37","author":"Kciuk","year":"2022","journal-title":"J. Enzym. Inhib. Med. Chem."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1064","DOI":"10.1158\/2326-6066.CIR-18-0657","article-title":"Targeting hypoxia-induced carbonic anhydrase IX enhances immune-checkpoint blockade locally and systemically","volume":"7","author":"Chafe","year":"2019","journal-title":"Cancer Immunol. Res."},{"key":"ref_13","first-page":"100131","article-title":"Tumor associated carbonic anhydrase inhibitors: Rational approaches, design strategies, structure activity relationship and mechanistic insights","volume":"18","author":"Nerella","year":"2024","journal-title":"Eur. J. Med. Chem. Rep."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Al-Sanea, M.M., Chilingaryan, G., Abelyan, N., Arakelov, G., Sahakyan, H., Arakelov, V.G., Nazaryan, K., Hussein, S., Alazmi, G.M., and Alsharari, H.E. (2021). Identification of non-classical hCA XII inhibitors using combination of computational approaches for drug design and discovery. Sci. Rep., 11.","DOI":"10.1038\/s41598-021-94809-x"},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Courcier, J., de la Taille, A., Nourieh, M., Leguerney, I., Lassau, N., and Ingels, A. (2020). Carbonic Anhydrase IX in Renal Cell Carcinoma, Implications for Disease Management. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21197146"},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Singh, P., Nerella, S.G., Swain, B., Angeli, A., Ullah, Q., Supuran, C.T., and Arifuddin, M. (2024). Design, synthesis and in vitro evaluation of novel thiazole-coumarin hybrids as selective and potent human carbonic anhydrase IX and XII inhibitors. Int. J. Biol. Macromol., 268.","DOI":"10.1016\/j.ijbiomac.2024.131548"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"138680","DOI":"10.1016\/j.molstruc.2024.138680","article-title":"Novel 1,2,4-triazole-maleamic acid derivatives: Synthesis and evaluation as anticancer agents with carbonic anhydrase inhibitory activity","volume":"1313","author":"Tapera","year":"2024","journal-title":"J. Mol. Struct."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1570","DOI":"10.1016\/j.bmc.2012.04.044","article-title":"Structure, function and applications of carbonic anhydrase isozymes","volume":"21","author":"Hassan","year":"2013","journal-title":"Bioorg. Med. Chem."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Begines, P., Bonardi, A., Nocentini, A., Gratteri, P., Giovannuzzi, S., Ronca, R., Tavani, C., Massardi, M.L., L\u00f3pez, \u00d3., and Supuran, C.T. (2023). Design and synthesis of sulfonamides incorporating a biotin moiety: Carbonic anhydrase inhibitory effects, antiproliferative activity and molecular modeling studies. Bioorg. Med. Chem., 94.","DOI":"10.1016\/j.bmc.2023.117467"},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Abdelhakeem, M.M., Morcoss, M.M., Hanna, D.A., and Lamie, P.F. (2024). Design, synthesis and in silico insights of novel 1,2,3-triazole benzenesulfonamide derivatives as potential carbonic anhydrase IX and XII inhibitors with promising anticancer activity. Bioorg. Chem., 144.","DOI":"10.1016\/j.bioorg.2024.107154"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"23257","DOI":"10.1039\/D4RA04548C","article-title":"Synthesis and evaluation of sulfonamide derivatives of quinoxaline 1,4-dioxides as carbonic anhydrase inhibitors","volume":"14","author":"Buravchenko","year":"2024","journal-title":"RSC Adv."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"116527","DOI":"10.1016\/j.ejmech.2024.116527","article-title":"A new framework for novel analogues of pazopanib as potent and selective human carbonic anhydrase inhibitors: Design, repurposing rational, synthesis, crystallographic, in vivo and in vitro biological assessments","volume":"274","author":"Hefny","year":"2024","journal-title":"Eur. J. Med. Chem."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"113997","DOI":"10.1016\/j.ejmech.2021.113997","article-title":"Synthesis, biological evaluation, and in silico studies of potential activators of apoptosis and carbonic anhydrase inhibitors on isatin-5-sulfonamide scaffold","volume":"228","author":"Krymov","year":"2022","journal-title":"Eur. J. Med. Chem."},{"key":"ref_24","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. (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_25","doi-asserted-by":"crossref","unstructured":"Ibrahim, S.A., Al-Mhyawi, S.R., and Atlam, F.M. (2023). New imidazole-2-ones and their 2-thione analogues as anticancer agents and CAIX inhibitors: Synthesis, in silico ADME and molecular modeling studies. Bioorg. Chem., 141.","DOI":"10.1016\/j.bioorg.2023.106872"},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Akocak, S., G\u00fczel-Akdemir, \u00d6., Sanku, R.K., Russom, S.S., Iorga, B.I., Supuran, C.T., and Ilies, M.A. (2020). Pyridinium derivatives of 3-aminobenzenesulfonamide are nanomolar-potent inhibitors of tumor-expressed carbonic anhydrase isozymes CA IX and CA XII. Bioorg. Chem., 103.","DOI":"10.1016\/j.bioorg.2020.104204"},{"key":"ref_27","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_28","doi-asserted-by":"crossref","first-page":"1026","DOI":"10.1177\/2472555220918836","article-title":"Identification of novel carbonic anhydrase IX inhibitors using high-throughput screening of pooled compound libraries by DNA-linked inhibitor antibody assay (DIANA)","volume":"25","author":"Tykvart","year":"2020","journal-title":"Slas Discov. Adv. Sci. Drug Discov."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"114004","DOI":"10.1016\/j.ejmech.2021.114004","article-title":"Application of the dual-tail approach for the design and synthesis of novel Thiopyrimidine\u2013Benzenesulfonamide hybrids as selective carbonic anhydrase inhibitors","volume":"228","author":"Omar","year":"2022","journal-title":"Eur. J. Med. Chem."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"114190","DOI":"10.1016\/j.ejmech.2022.114190","article-title":"Discovery of new carbonic anhydrase IX inhibitors as anticancer agents by toning the hydrophobic and hydrophilic rims of the active site to encounter the dual-tail approach","volume":"232","author":"Tawfik","year":"2022","journal-title":"Eur. J. Med. Chem."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1555","DOI":"10.1080\/14756366.2020.1801674","article-title":"Inhibitory activity against carbonic anhydrase IX and XII as a candidate selection criterion in the development of new anticancer agents","volume":"35","author":"Krasavin","year":"2020","journal-title":"J. Enzym. Inhib. Med. Chem."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Carta, F., Vullo, D., and Angeli, A. (2021). Design, synthesis, and biological evaluation of selective hCA IX inhibitors. pH-Interfering Agents as Chemosensitizers in Cancer Therapy, Academic Press.","DOI":"10.1016\/B978-0-12-820701-7.00014-2"},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Kumar, A., Siwach, K., Supuran, C.T., and Sharma, P.K. (2022). A decade of tail-approach based design of selective as well as potent tumor associated carbonic anhydrase inhibitors. Bioorg. Chem., 126.","DOI":"10.1016\/j.bioorg.2022.105920"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"24003","DOI":"10.1039\/D3RA02528D","article-title":"Tail-approach based design, synthesis, and cytotoxic evaluation of novel disubstituted and trisubstituted 1,3-thiazole benzenesulfonamide derivatives with suggested carbonic anhydrase IX inhibition mechanism","volume":"13","author":"Bondock","year":"2023","journal-title":"RSC Adv."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"2200439","DOI":"10.1002\/ardp.202200439","article-title":"Tail approach synthesis of triazolylthiazolotriazole bearing benzenesulfonamides as carbonic anhydrase inhibitors capable of inducing apoptosis","volume":"356","author":"Vats","year":"2023","journal-title":"Arch. Pharm."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"794","DOI":"10.1016\/j.bioorg.2019.04.002","article-title":"Novel synthesized SLC-0111 thiazole and thiadiazole analogues: Determination of their carbonic anhydrase inhibitory activity and molecular modeling studies","volume":"87","author":"Eldehna","year":"2019","journal-title":"Bioorg. Chem."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1007\/s11030-023-10761-0","article-title":"An efficient eco-friendly, simple, and green synthesis of some new spiro-N-(4-sulfamoyl-phenyl)-1,3,4-thiadiazole-2-carboxamide derivatives as potential inhibitors of SARS-CoV-2 proteases: Drug-likeness, pharmacophore, molecular docking, and DFT exploration","volume":"28","author":"Enaili","year":"2024","journal-title":"Mol. Divers."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"2300208","DOI":"10.1002\/ardp.202300208","article-title":"Harnessing pyrimidine as a building block for histone deacetylase inhibitors","volume":"356","author":"Badran","year":"2023","journal-title":"Arch. Pharm."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1547","DOI":"10.1016\/S0006-2952(03)00510-0","article-title":"DNA damage-triggered apoptosis: Critical role of DNA repair, double-strand breaks, cell proliferation and signaling","volume":"66","author":"Kaina","year":"2003","journal-title":"Biochem. Pharmacol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1080\/01926230701320337","article-title":"Apoptosis: A review of programmed cell death","volume":"35","author":"Elmore","year":"2007","journal-title":"Toxicol. Pathol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"3246","DOI":"10.2174\/138161210793429841","article-title":"Recent advances in structural studies of the carbonic anhydrase family: The crystal structure of human CA IX and CA XIII","volume":"16","author":"TSupuran","year":"2010","journal-title":"Curr. Pharm. Des."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1021\/bi00853a037","article-title":"The catalytic versatility of erythrocyte carbonic anhydrase. II. Kinetic studies of the enzyme-catalyzed hydration of pyridine aldehydes","volume":"6","author":"Pocker","year":"1967","journal-title":"Biochemistry"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"115805","DOI":"10.1016\/j.ejmech.2023.115805","article-title":"Exploring novel anticancer pyrazole benzenesulfonamides featuring tail approach strategy as carbonic anhydrase inhibitors","volume":"261","author":"Ahmed","year":"2023","journal-title":"Eur. J. Med. Chem."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"115707","DOI":"10.1016\/j.ejmech.2023.115707","article-title":"Discovery of indolinone-bearing benzenesulfonamides as new dual carbonic anhydrase and VEGFR-2 inhibitors possessing anticancer and pro-apoptotic properties","volume":"259","author":"Saied","year":"2023","journal-title":"Eur. J. Med. Chem."},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Al-Hakkani, M.F., Ahmed, N., Abbas, A.A., Hassan, M.H., Aziz, H.A., Elshamsy, A.M., Khalifa, H.O., Abdelshakour, M.A., Saddik, M.S., and Elsayed, M.M. (2023). Synthesis, Physicochemical Characterization using a Facile Validated HPLC Quantitation Analysis Method of 4-Chloro-phenylcarbamoyl-methyl Ciprofloxacin and Its Biological Investigations. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms241914818"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"467","DOI":"10.2144\/000112401","article-title":"Isolation and solubilization of proteins after TRIzol\u00ae extraction of RNA and DNA from patient material following prolonged storage","volume":"42","author":"Hummon","year":"2007","journal-title":"Biotechniques"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.clinmicnews.2011.12.002","article-title":"Assessment of DNA yield and purity: An overlooked detail of PCR troubleshooting","volume":"34","author":"Pessarakli","year":"2012","journal-title":"Clin. Microbiol. Newsl."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1016\/0378-1119(90)90145-H","article-title":"Use of uracil DNA glycosylase to control carry-over contamination in polymerase chain reactions","volume":"93","author":"Longo","year":"1990","journal-title":"Gene"},{"key":"ref_49","first-page":"18","article-title":"Journal of Umm Al-Qura University for Medical Sciences","volume":"7","author":"Almasmoum","year":"2021","journal-title":"J. Umm Al-Qura Univ. Med. Sci."},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Ali, D.M., Aziz, H.A., Br\u00e4se, S., Al Bahir, A., Alkhammash, A., Abuo-Rahma, G.E., Elshamsy, A.M., Hashem, H., and Abdelmagid, W.M. (2024). Unveiling the Anticancer Potential of a New Ciprofloxacin-Chalcone Hybrid as an Inhibitor of Topoisomerases I & II and Apoptotic Inducer. Molecules, 29.","DOI":"10.3390\/molecules29225382"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/2\/863\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,8]],"date-time":"2025-10-08T10:32:28Z","timestamp":1759919548000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/2\/863"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,1,20]]},"references-count":50,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2025,1]]}},"alternative-id":["ijms26020863"],"URL":"https:\/\/doi.org\/10.3390\/ijms26020863","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,1,20]]}}}