{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T21:50:44Z","timestamp":1789681844126,"version":"4.0.1"},"reference-count":59,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2026,4,23]],"date-time":"2026-04-23T00:00:00Z","timestamp":1776902400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004837","name":"Ministerio de Ciencia, Innovaci\u00f3n y Universidades","doi-asserted-by":"publisher","award":["PID2023-147401OB-I00"],"award-info":[{"award-number":["PID2023-147401OB-I00"]}],"id":[{"id":"10.13039\/501100004837","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004837","name":"Ministerio de Ciencia, Innovaci\u00f3n y Universidades","doi-asserted-by":"publisher","award":["PID2021-123059OB-I00"],"award-info":[{"award-number":["PID2021-123059OB-I00"]}],"id":[{"id":"10.13039\/501100004837","id-type":"DOI","asserted-by":"publisher"}]},{"award":["PID2023-147401OB-I00"],"award-info":[{"award-number":["PID2023-147401OB-I00"]}],"id":[{"id":"https:\/\/ror.org\/05r0vyz12","id-type":"ROR","asserted-by":"publisher"}]},{"award":["PID2021-123059OB-I00"],"award-info":[{"award-number":["PID2021-123059OB-I00"]}],"id":[{"id":"https:\/\/ror.org\/05r0vyz12","id-type":"ROR","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100011011","name":"Junta de Andaluc\u00eda","doi-asserted-by":"publisher","award":["FQM-134"],"award-info":[{"award-number":["FQM-134"]}],"id":[{"id":"10.13039\/501100011011","id-type":"DOI","asserted-by":"publisher"}]},{"award":["FQM-134"],"award-info":[{"award-number":["FQM-134"]}],"id":[{"id":"https:\/\/ror.org\/01jem9c82","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Selective inhibition of the tumour-associated carbonic anhydrase (CA) isoforms IX and XII, which are overexpressed in hypoxic tumours, has emerged as a promising strategy for the development of novel anticancer agents. Among the diverse CA inhibitors reported to date, coumarins have attracted particular attention. These chromenone derivatives, widely distributed in phytochemicals, display a broad range of biological activities and are known to act as suicide inhibitors of CAs. Following the tail approach, we designed a series of hybrid compounds combining a coumarin core with an N-arylthioureido scaffold located at the C-7 position and investigated how structural variations\u2014including substituents on the coumarin and aromatic moieties, tether length, and urea\/thiourea isosterism\u2014influence their biological properties (CA inhibition and antiproliferative activity). Substituted coumarins at C-3 and C-4 were efficiently prepared via Pechmann condensation, while the thioureido motif was introduced using various aryl isothiocyanates as key synthetic intermediates. The lead compound, featuring a dimethylated coumarin, a pentyl linker, and an N-(p-tolyl)thioureido residue, inhibited the target enzymes in the low- to mid-nanomolar range (Ki = 6.0 and 49.9 nM, respectively), displaying selectivity indexes (S.I.s) surpassing those of the reference drug acetazolamide (AAZ). Moreover, it exhibited potent antiproliferative activity, with GI50 values in the low micromolar range (1.9\u20133.5 \u00b5M) against both drug-sensitive and multidrug-resistant cancer cell lines. Label-free three-dimensional holotomographic microscopy revealed that this compound triggers slow apoptosis, leading to cell death after approximately 20 h of exposure.<\/jats:p>","DOI":"10.3390\/ijms27093743","type":"journal-article","created":{"date-parts":[[2026,4,23]],"date-time":"2026-04-23T10:10:17Z","timestamp":1776939017000},"page":"3743","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Coumarin\u2013Thiourea Hybrids: Structural Features Governing CA Inhibition and Antiproliferative Effects"],"prefix":"10.3390","volume":"27","author":[{"given":"Alma","family":"Fuentes-Aguilar","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 Puebla, Puebla 72570, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rebecca","family":"Colombo","sequence":"additional","affiliation":[{"name":"Departamento de Qu\u00edmica Org\u00e1nica, Facultad de Qu\u00edmica, Universidad de Sevilla, Apartado 1203, E-41071 Seville, Spain"},{"name":"NEUROFARBA Department, Sezione di Scienze Farmaceutiche e Nutraceutiche, University of Florence, 50019 Florence, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9792-5194","authenticated-orcid":false,"given":"Aday","family":"Gonz\u00e1lez-Bakker","sequence":"additional","affiliation":[{"name":"BioLab, Instituto Universitario de Bio-Org\u00e1nica \u201cAntonio Gonz\u00e1lez\u201d (IUBO-AG), Universidad de La Laguna, c\/Astrof\u00edsico Francisco S\u00e1nchez 2, E-38206 La Laguna, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7975-1960","authenticated-orcid":false,"given":"Adri\u00e1n","family":"Puerta","sequence":"additional","affiliation":[{"name":"BioLab, Instituto Universitario de Bio-Org\u00e1nica \u201cAntonio Gonz\u00e1lez\u201d (IUBO-AG), Universidad de La Laguna, c\/Astrof\u00edsico Francisco S\u00e1nchez 2, E-38206 La Laguna, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1376-9671","authenticated-orcid":false,"given":"Pen\u00e9lope","family":"Merino-Montiel","sequence":"additional","affiliation":[{"name":"Facultad de Ciencias Qu\u00edmicas, Ciudad Universitaria, Benem\u00e9rita Universidad Aut\u00f3noma de Puebla, Puebla 72570, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3080-9252","authenticated-orcid":false,"given":"Sara","family":"Montiel-Smith","sequence":"additional","affiliation":[{"name":"Facultad de Ciencias Qu\u00edmicas, Ciudad Universitaria, Benem\u00e9rita Universidad Aut\u00f3noma de Puebla, Puebla 72570, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos\u00e9 L.","family":"Vega-B\u00e1ez","sequence":"additional","affiliation":[{"name":"Facultad de Ciencias Qu\u00edmicas, Ciudad Universitaria, Benem\u00e9rita Universidad Aut\u00f3noma de Puebla, Puebla 72570, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0669-7481","authenticated-orcid":false,"given":"Simone","family":"Giovannuzzi","sequence":"additional","affiliation":[{"name":"NEUROFARBA Department, Sezione di Scienze Farmaceutiche e Nutraceutiche, University of Florence, 50019 Florence, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3342-702X","authenticated-orcid":false,"given":"Alessio","family":"Nocentini","sequence":"additional","affiliation":[{"name":"NEUROFARBA Department, Sezione di Scienze Farmaceutiche e Nutraceutiche, University of Florence, 50019 Florence, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos\u00e9 G.","family":"Fern\u00e1ndez-Bola\u00f1os","sequence":"additional","affiliation":[{"name":"Departamento de Qu\u00edmica Org\u00e1nica, Facultad de Qu\u00edmica, Universidad de Sevilla, Apartado 1203, E-41071 Seville, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4262-0323","authenticated-orcid":false,"given":"Claudiu T.","family":"Supuran","sequence":"additional","affiliation":[{"name":"NEUROFARBA Department, Sezione di Scienze Farmaceutiche e Nutraceutiche, University of Florence, 50019 Florence, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6268-6552","authenticated-orcid":false,"given":"Jos\u00e9 M.","family":"Padr\u00f3n","sequence":"additional","affiliation":[{"name":"BioLab, Instituto Universitario de Bio-Org\u00e1nica \u201cAntonio Gonz\u00e1lez\u201d (IUBO-AG), Universidad de La Laguna, c\/Astrof\u00edsico Francisco S\u00e1nchez 2, E-38206 La Laguna, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"\u00d3scar","family":"L\u00f3pez","sequence":"additional","affiliation":[{"name":"Departamento de Qu\u00edmica Org\u00e1nica, Facultad de Qu\u00edmica, Universidad de Sevilla, Apartado 1203, E-41071 Seville, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,4,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1113\/jphysiol.1933.sp003077","article-title":"Carbonic Anhydrase. Its Preparation and Properties","volume":"80","author":"Meldrum","year":"1933","journal-title":"J. Physiol."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Capasso, C. (2023). Carbonic Anhydrases: A Superfamily of Ubiquitous Enzymes. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24087014"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1007\/978-94-007-7359-2_3","article-title":"Catalytic mechanism of \u03b1-class carbonic anhydrases: CO2 hydration and proton transfer","volume":"75","author":"Boone","year":"2014","journal-title":"Subcell. Biochem."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Supuran, C.T. (2023). Carbonic anhydrase versatility: From pH regulation to CO2 sensing and metabolism. Front. Mol. Biosci., 10.","DOI":"10.3389\/fmolb.2023.1326633"},{"key":"ref_5","first-page":"95","article-title":"Carbonic anhydrase and respiratory gas exchange","volume":"Volume 17","author":"Perry","year":"1998","journal-title":"Fish Physiology-Fish Respiration"},{"key":"ref_6","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 modeling. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20153841"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1016\/j.molp.2016.09.001","article-title":"Plant carbonic anhydrases: Structures, locations, evolution, and physiological roles","volume":"10","author":"DiMario","year":"2017","journal-title":"Mol. Plant"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Weerasooriya, H.N., Longstreth, D.J., DiMario, R.J., Rosati, V.C., Cassel, B.A., and Moroney, J.V. (2024). Carbonic anhydrases in the cell wall and plasma membrane of Arabidopsis thaliana are required for optimal plant growth on low CO2. Front. Mol. Biosci., 11.","DOI":"10.3389\/fmolb.2024.1267046"},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Lee, S.-K., Boron, W.F., and Occhipinti, R. (2023). Potential novel role of membrane-associated carbonic anhydrases in the kidney. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24044251"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1038\/s44324-025-00051-8","article-title":"Characterization and treatment monitoring of ureagenesis disorders using stable isotopes","volume":"3","author":"Allegri","year":"2025","journal-title":"npj Metab. Health Dis."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1113\/JP283579","article-title":"Mitochondrial carbonic anhydrase VA and VB: Properties and roles in health and disease","volume":"601","author":"Aspatwar","year":"2023","journal-title":"J. Physiol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"4129","DOI":"10.1111\/febs.15720","article-title":"Functional partnership between carbonic anhydrase and malic enzyme in promoting gluconeogenesis in Leishmania major","volume":"288","author":"Mondal","year":"2021","journal-title":"FEBBS J."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"725","DOI":"10.1517\/13543776.2013.790957","article-title":"Antiobesity carbonic anhydrase inhibitors: A literature and patent review","volume":"23","author":"Scozzafava","year":"2013","journal-title":"Expert Opin. Ther. Pat."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1070","DOI":"10.1139\/b91-137","article-title":"The catalytic mechanism of carbonic anhydrase","volume":"69","author":"Silverman","year":"1991","journal-title":"Can. J. Bot."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"100918","DOI":"10.1016\/j.clet.2025.100918","article-title":"Evaluation of enhanced absorption of carbon dioxide using carbonic anhydrase in aqueous solutions of 2-amino-2-methyl-1-propanol","volume":"25","author":"Fonck","year":"2025","journal-title":"Clean. Eng. Technol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"128514","DOI":"10.1016\/j.jenvman.2025.128514","article-title":"Magnetic halloysite-functionalized carbonic anhydrase nanobiocatalyst for superior stability and sustainable CO2 sequestration","volume":"398","author":"Sillu","year":"2026","journal-title":"J. Environ. Manag."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"2213","DOI":"10.1007\/s10311-024-01755-x","article-title":"Carbon dioxide sequestration with carbonic anhydrase nanobiocatalysts: A review","volume":"22","author":"Sillu","year":"2024","journal-title":"Environ. Chem. Lett."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"39708","DOI":"10.1021\/jacs.5c13405","article-title":"Bioinspired carbonic anhydrase mimics with Zr\u2013OH sites and size-tunable nanopockets for efficient bidirectional catalysis of CO2 hydration","volume":"147","author":"Xu","year":"2025","journal-title":"J. Am. Chem. Soc."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"83093","DOI":"10.1007\/s11356-023-28122-7","article-title":"Carbonic anhydrase as a tool to mitigate global warming","volume":"30","author":"Ali","year":"2023","journal-title":"Environ. Sci. Pollut. Res."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"108224","DOI":"10.1016\/j.bioorg.2025.108224","article-title":"Carbonic anhydrase inhibitors: Structural insights and therapeutic potential","volume":"156","author":"Singh","year":"2025","journal-title":"Bioorg. Chem."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"2166503","DOI":"10.1080\/14756366.2023.2166503","article-title":"Click chemistry approaches for developing carbonic anhydrase inhibitors and their applications","volume":"38","author":"Angeli","year":"2023","journal-title":"J. Enzym. Inhib. Med. Chem."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1016\/bs.enz.2024.05.003","article-title":"Bacterial \u03b9-CAs","volume":"Volume 55","author":"Supuran","year":"2024","journal-title":"The Enzymes"},{"key":"ref_23","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_24","doi-asserted-by":"crossref","unstructured":"Kircheva, N., Angelova, S., and Dudev, T. (2024). Carbonic anhydrases: Different active sites, same metal selectivity rules. Molecules, 29.","DOI":"10.3390\/molecules29091995"},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Garc\u00eda-Llorca, A., Carta, F., Supuran, C.T., and Eysteinsson, T. (2024). Carbonic anhydrase, its inhibitors and vascular function. Front. Mol. Biosci., 11.","DOI":"10.3389\/fmolb.2024.1338528"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"190407","DOI":"10.1098\/rsos.190407","article-title":"Kinetic study of catalytic CO2 hydration by metal-substituted biomimetic carbonic anhydrase model complexes","volume":"6","author":"Park","year":"2019","journal-title":"R. Soc. Open Sci."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"150","DOI":"10.1021\/acs.chemrev.4c00278","article-title":"Multiple binding modes of inhibitors to human carbonic anhydrases: An update on the design of isoform-specific modulators of activity","volume":"125","author":"DAmbrosio","year":"2025","journal-title":"Chem. Rev."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1007\/978-94-007-7359-2_8","article-title":"Carbonic anhydrase related proteins: Molecular biology and evolution","volume":"75","author":"Aspatwar","year":"2014","journal-title":"Subcell. Biochem."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1332","DOI":"10.1136\/bjophthalmol-2021-319530","article-title":"Topical carbonic anhydrase inhibitors and glaucoma in 2021: Where do we stand?","volume":"106","author":"Stoner","year":"2022","journal-title":"Br. J. Ophthalmol."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Ciccone, L., Cerri, C., Nencetti, S., and Orlandini, E. (2021). Carbonic anhydrase inhibitors and epilepsy: State of the art and future perspectives. Molecules, 26.","DOI":"10.3390\/molecules26216380"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"e17429","DOI":"10.7717\/peerj.17429","article-title":"Sucrose rinse modulates the salivary behavior of carbonic anhydrase VI and its buffering capacity: A longitudinal study in 4 to 6.5-year-old children","volume":"12","author":"Zancope","year":"2024","journal-title":"PeerJ"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"16873","DOI":"10.1021\/acs.jmedchem.4c01866","article-title":"Enhanced recognition memory through dual modulation of brain carbonic anhydrases and cholinesterases","volume":"67","author":"Nocentini","year":"2024","journal-title":"J. Med. Chem."},{"key":"ref_33","first-page":"100131","article-title":"Tumor associated carbonic anhydrase inhibitors: Rational approaches, design strategies, structure activity relationship and mechanistic insights","volume":"10","author":"Nerella","year":"2024","journal-title":"Eur. J. Med. Chem. Rep."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"176","DOI":"10.1021\/acsinfecdis.5c00736","article-title":"Bacterial carbonic anhydrase inhibitor CAI0019 demonstrates efficacy in Enterococcus faecium septicemic peritonitis mouse model while sparing the microbiome","volume":"12","author":"Abutaleb","year":"2026","journal-title":"ACS Infect. Dis."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"905","DOI":"10.1016\/S0002-9440(10)64038-2","article-title":"Expression of hypoxia-inducible cell-surface transmembrane carbonic anhydrases in human cancer","volume":"158","author":"Ivanov","year":"2001","journal-title":"Am. J. Pathol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"622","DOI":"10.1038\/s41416-018-0216-5","article-title":"Carbonic anhydrase IX is a pH-stat that sets an acidic tumour extracellular pH in vivo","volume":"119","author":"Lee","year":"2018","journal-title":"Br. J. Cancer"},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Numprasit, W., Yangngam, S., Prasopsiri, J., Quinn, J.A., Edwards, J., and Thuwajit, C. (2023). Carbonic anhydrase IX-related tumoral hypoxia predicts worse prognosis in breast cancer: A systematic review and meta-analysis. Front. Med., 10.","DOI":"10.3389\/fmed.2023.1087270"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"2598","DOI":"10.1158\/1535-7163.MCT-18-0533","article-title":"Carbonic an-hydrase XII inhibitors overcome P-glycoprotein\u2013mediated resistance to temozolomide in glioblastoma","volume":"17","author":"Salaroglio","year":"2018","journal-title":"Mol. Cancer Ther."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1889","DOI":"10.1021\/acsmedchemlett.5c00443","article-title":"Human carbonic anhydrase inhibitors","volume":"16","author":"Supuran","year":"2025","journal-title":"ACS Med. Chem. Lett."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1016\/0278-6915(94)90074-4","article-title":"Studies on the acute effects of coumarin and some coumarin derivatives in the rat","volume":"32","author":"Lake","year":"1994","journal-title":"Food Chem. Toxicol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"108319","DOI":"10.1016\/j.bioorg.2025.108319","article-title":"Thiourea compounds as multifaceted bioactive agents in medicinal chemistry","volume":"158","author":"Khan","year":"2025","journal-title":"Bioorg. Chem."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1046","DOI":"10.1039\/D1MD00058F","article-title":"Recent advances in urea- and thiourea-containing compounds: Focus on innovative approaches in medicinal chemistry and organic synthesis","volume":"12","author":"Ronchetti","year":"2021","journal-title":"RSC Med. Chem."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1016\/j.ejmech.2017.10.063","article-title":"Synthesis of unprecedented steroidal spiro heterocycles as potential antiproliferative drugs","volume":"143","year":"2018","journal-title":"Eur. J. Med. Chem."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"21795","DOI":"10.1021\/acsomega.5c01648","article-title":"Molecular modeling and in vitro evaluation of thioureas and arylthioureas as urease inhibitors","volume":"10","author":"Fabris","year":"2025","journal-title":"ACS Omega"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"798","DOI":"10.2174\/1385272820666151026224227","article-title":"Recent advances in the synthesis of coumarin derivatives via Pechmann condensation","volume":"20","author":"Zambare","year":"2016","journal-title":"Curr. Org. Chem."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"168","DOI":"10.1080\/14756366.2021.1998026","article-title":"2-Aminobenzoxazole-appended coumarins as potent and selective inhibitors of tumour-associated carbonic anhydrases","volume":"37","author":"Puerta","year":"2022","journal-title":"J. Enzym. Inhib. Med. Chem."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"107168","DOI":"10.1016\/j.bioorg.2024.107168","article-title":"Coumarins-lipophilic cations conjugates: Efficient mitocans targeting carbonic anhydrases","volume":"145","author":"Puerta","year":"2024","journal-title":"Bioorg. Chem."},{"key":"ref_48","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_49","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1016\/0022-2860(82)85231-9","article-title":"Spectra and conformations of substituted thioureas","volume":"82","author":"Vassilev","year":"1982","journal-title":"J. Mol. Struct."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"118453","DOI":"10.1016\/j.bmc.2025.118453","article-title":"Selenoureido-N-alkyl-3,4,5-trihydroxypiperidines: Probing their dual-target role in Gaucher disease","volume":"132","author":"Pratesi","year":"2026","journal-title":"Bioorg. Med. Chem."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"7658","DOI":"10.1039\/D2DT00401A","article-title":"The effect of halogenation of salicylaldehyde on the antiproliferative activities of {\u0394\/\u039b-[Ru(bpy)2(X,Y-sal)]BF4} complexes","volume":"51","author":"Shool","year":"2022","journal-title":"Dalton Trans."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"232","DOI":"10.1021\/acs.chemrev.7b00032","article-title":"Development of halogenase enzymes for use in synthesis","volume":"118","author":"Latham","year":"2018","journal-title":"Chem. Rev."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1209","DOI":"10.1080\/17460441.2021.1922384","article-title":"Advances in the discovery of novel agents for the treatment of glaucoma","volume":"16","author":"Mincione","year":"2021","journal-title":"Expert Opin. Drug Discov."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"2154603","DOI":"10.1080\/14756366.2022.2154603","article-title":"Discovery of new 6-ureido\/amidocoumarins as highly potent and selective inhibitors for the tumour-relevant carbonic anhydrases IX and XII","volume":"38","author":"Kim","year":"2023","journal-title":"J. Enzym. Inhib. Med. Chem."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1252","DOI":"10.1002\/cmdc.202000915","article-title":"Coumarin-Thiourea Hybrids Show Potent CarbonicAnhydrase IX and XIII Inhibitory Action","volume":"16","author":"Thacker","year":"2021","journal-title":"ChemMedChem"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"2176","DOI":"10.1021\/om100106e","article-title":"NMR Chemical shifts of trace impurities: Common laboratory solvents, organics, and gases in deuterated solvents relevant to the organommetallic chemist","volume":"29","author":"Fulmer","year":"2010","journal-title":"Organometallics"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"107089","DOI":"10.1016\/j.bioorg.2023.107089","article-title":"Identification of thienopyrimidine derivatives tethered with sulfonamide and other moieties as carbonic anhydrase inhibitors: Design, synthesis and anti-proliferative activity","volume":"144","author":"Higazy","year":"2024","journal-title":"Bioorg. Chem."},{"key":"ref_58","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."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"116807","DOI":"10.1016\/j.bcp.2025.116807","article-title":"Multimodal antiproliferative effects of oleanolic acid mitocans: In vitro and in vivo studies","volume":"234","author":"Puerta","year":"2025","journal-title":"Biochem. Pharmacol."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/9\/3743\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,8]],"date-time":"2026-05-08T04:11:23Z","timestamp":1778213483000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/9\/3743"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,23]]},"references-count":59,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2026,5]]}},"alternative-id":["ijms27093743"],"URL":"https:\/\/doi.org\/10.3390\/ijms27093743","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4,23]]}}}