{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T07:59:01Z","timestamp":1790150341831,"version":"4.0.1"},"reference-count":60,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2021,12,31]],"date-time":"2021-12-31T00:00:00Z","timestamp":1640908800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003407","name":"Ministry of Education, Universities and Research","doi-asserted-by":"publisher","award":["PRIN: prot. 2017XYBP2R"],"award-info":[{"award-number":["PRIN: prot. 2017XYBP2R"]}],"id":[{"id":"10.13039\/501100003407","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>We report here a new drug design strategy for producing membrane-impermeant carbonic anhydrase (CA; EC 4.2.1.1) inhibitors selectively targeting the tumor-associated, membrane-bound human CAs IX and XII over off-target cytosolic isoforms. To date, this approach has only been pursued by including permanent positively charged pyridinium type or highly hydrophilic glycosidic moieties into the structure of aromatic sulfonamide CA inhibitors (CAIs). Aliphatic (propyl and butyl) sulfonic acid tails, deprotonated at physiological pH, were thus incorporated onto a benzenesulfonamide scaffold by a common 1,2,3-triazole linker and different types of spacers. Twenty such derivatives were synthesized and tested for their inhibition of target (hCAs IV, IX, and XII) and off-target CAs (hCAs I and II). Most sulfonate CAIs induced a potent inhibition of hCAs II, IX, and XII up to a low nanomolar KI range (0.9\u2013459.4 nM) with a limited target\/off-target CA selectivity of action. According to the drug design schedule, a subset of representative derivatives was assessed for their cell membrane permeability using Caco-2 cells and a developed FIA-MS\/MS method. The complete membrane impermeability of the sulfonate tailed CAIs (\u226598%) validated these negatively charged moieties as being suitable for achieving, in vivo, the selective targeting of the tumor-associated CAs over off-target ones.<\/jats:p>","DOI":"10.3390\/ijms23010461","type":"journal-article","created":{"date-parts":[[2022,1,7]],"date-time":"2022-01-07T01:15:26Z","timestamp":1641518126000},"page":"461","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":26,"title":["Aromatic Sulfonamides including a Sulfonic Acid Tail: New Membrane Impermeant Carbonic Anhydrase Inhibitors for Targeting Selectively the Cancer-Associated Isoforms"],"prefix":"10.3390","volume":"23","author":[{"given":"Simone","family":"Giovannuzzi","sequence":"first","affiliation":[{"name":"NEUROFARBA Department, Section of Pharmaceutical and Nutraceutical Sciences, University of Florence, Polo Scientifico, Via U. Schiff 6, Sesto Fiorentino, 50019 Firenze, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mario","family":"D\u2019Ambrosio","sequence":"additional","affiliation":[{"name":"NEUROFARBA Department, Section of Pharmacology and Toxicology, University of Florence, Viale Gaetano Pieraccini 6, 50100 Firenze, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1232-8778","authenticated-orcid":false,"given":"Cristina","family":"Luceri","sequence":"additional","affiliation":[{"name":"NEUROFARBA Department, Section of Pharmacology and Toxicology, University of Florence, Viale Gaetano Pieraccini 6, 50100 Firenze, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1564-7301","authenticated-orcid":false,"given":"Sameh Mohamed","family":"Osman","sequence":"additional","affiliation":[{"name":"Chemistry Department, College of Science, King Saud University, P.O. Box 2455, Riyadh 11451, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0057-6531","authenticated-orcid":false,"given":"Marco","family":"Pallecchi","sequence":"additional","affiliation":[{"name":"NEUROFARBA Department, Section of Pharmaceutical and Nutraceutical Sciences, University of Florence, Polo Scientifico, Via U. Schiff 6, Sesto Fiorentino, 50019 Firenze, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5631-8769","authenticated-orcid":false,"given":"Gianluca","family":"Bartolucci","sequence":"additional","affiliation":[{"name":"NEUROFARBA Department, Section of Pharmaceutical and Nutraceutical Sciences, University of Florence, Polo Scientifico, Via U. Schiff 6, Sesto Fiorentino, 50019 Firenze, 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, Section of Pharmaceutical and Nutraceutical Sciences, University of Florence, Polo Scientifico, Via U. Schiff 6, Sesto Fiorentino, 50019 Firenze, Italy"}],"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, Section of Pharmaceutical and Nutraceutical Sciences, University of Florence, Polo Scientifico, Via U. Schiff 6, Sesto Fiorentino, 50019 Firenze, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,12,31]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"lgz004","DOI":"10.1093\/jncimonographs\/lgz004","article-title":"Chronic Systemic Symptoms in Head and Neck Cancer Patients","volume":"53","author":"Murphy","year":"2019","journal-title":"J. Natl. Cancer Inst. Monogr."},{"key":"ref_2","unstructured":"Ferlay, J., Laversanne, M., Ervik, M., Lam, F., Colombet, M., Mery, L., Pi\u00f1eros, M., Znaor, A., Soerjomataram, I., and Bray, F. (2021, December 15). Global Cancer Observatory: Cancer Tomorrow. Lyon, France: International Agency for Research on Cancer. Available online: https:\/\/gco.iarc.fr\/tomorrow."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"84","DOI":"10.18632\/oncotarget.422","article-title":"Recent developments in targeting Carbonic Anhydrase IX for cancer therapeutics","volume":"3","author":"McDonald","year":"2012","journal-title":"Oncotarget"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"963","DOI":"10.1080\/13543784.2018.1548608","article-title":"Carbonic anhydrase inhibitors as emerging agents for the treatment and imaging of hypoxic tumors","volume":"27","author":"Supuran","year":"2018","journal-title":"Expert Opin. Investig. Drugs"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"603","DOI":"10.2147\/JEP.S265620","article-title":"Experimental Carbonic Anhydrase Inhibitors for the Treatment of Hypoxic Tumors","volume":"12","author":"Supuran","year":"2020","journal-title":"J. Exp. Pharmacol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1080\/10409230091169186","article-title":"Hypoxia, clonal selection, and the role of HIF-1 in tumor progression","volume":"35","author":"Semenza","year":"2000","journal-title":"Crit. Rev. Biochem. Mol. Biol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"83","DOI":"10.2147\/HP.S93413","article-title":"The role of hypoxia in cancer progression, angiogenesis, metastasis, and resistance to therapy","volume":"3","author":"Muz","year":"2015","journal-title":"Hypoxia"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"849","DOI":"10.1016\/j.bmc.2014.12.030","article-title":"Saccharin: A lead compound for structure-based drug design of carbonic anhydrase IX inhibitors","volume":"23","author":"Mahon","year":"2015","journal-title":"Bioorg. Med. Chem."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"358","DOI":"10.1158\/0008-5472.CAN-08-2470","article-title":"Hypoxia-inducible Carbonic Anhydrase IX and XII promote tumor cell growth by counteracting acidosis through the regulation of the intracellular pH","volume":"69","author":"Chiche","year":"2009","journal-title":"Cancer Res."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"566","DOI":"10.1016\/j.tips.2006.09.002","article-title":"Targeting tumor-associated Carbonic Anhydrase IX in cancer therapy","volume":"27","author":"Thiry","year":"2006","journal-title":"Trends Pharmacol. Sci."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"168","DOI":"10.1038\/nrd2467","article-title":"Carbonic anhydrases: Novel therapeutic applications for inhibitors and activators","volume":"7","author":"Supuran","year":"2008","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"4421","DOI":"10.1021\/cr200176r","article-title":"Multiple binding modes of inhibitors to carbonic anhydrases: How to design specific drugs targeting 15 different isoforms?","volume":"112","author":"Alterio","year":"2012","journal-title":"Chem. Rev."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1175","DOI":"10.1080\/17460441.2019.1651289","article-title":"Advances in the structural annotation of human carbonic anhydrases and impact on future drug discovery","volume":"14","author":"Nocentini","year":"2019","journal-title":"Expert Opin. Drug Discov."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1233","DOI":"10.1042\/CS20210040","article-title":"Emerging role of carbonic anhydrase inhibitors","volume":"135","author":"Supuran","year":"2021","journal-title":"Clin. Sci."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"685","DOI":"10.2174\/138161208783877893","article-title":"Cancer-associated Carbonic Anhydrases and their inhibition","volume":"14","author":"Pastorek","year":"2008","journal-title":"Curr. Pharm. Des."},{"key":"ref_16","first-page":"2877","article-title":"Cloning and characterization of MN, a human tumor-associated protein with a domain homologous to carbonic anhydrase and putative helix-loop-helix DNA binding segment","volume":"9","author":"Pastorek","year":"1994","journal-title":"Oncogene"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"7608","DOI":"10.1073\/pnas.95.13.7608","article-title":"Human carbonic anhydrase XII: cDNA cloning, expression, and chromosomal localization of a carbonic anhydrase gene that is overexpressed in some renal cell cancers","volume":"95","author":"Tureci","year":"1998","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"2023","DOI":"10.1042\/BCJ20160115","article-title":"Structure and function of carbonic anhydrases","volume":"473","author":"Supuran","year":"2016","journal-title":"Biochem. J."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"332","DOI":"10.1016\/S0014-4827(03)00351-3","article-title":"Carbonic anhydrase IX reduces E-cadherin-mediated adhesion of MDCK cells via interaction with beta-catenin","volume":"290","author":"Zilka","year":"2003","journal-title":"Exp. Cell Res."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"439","DOI":"10.1016\/j.febslet.2004.10.043","article-title":"Hypoxia activates the capacity of tumor-associated carbonic anhydrase IX to acidify extracellular pH","volume":"577","author":"Casini","year":"2004","journal-title":"FEBS Lett."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"7558","DOI":"10.1158\/0008-5472.CAN-11-2520","article-title":"Phosphorylation of carbonic anhydrase IX controls its ability to mediate extracellular acidification in hypoxic tumors","volume":"71","author":"Ditte","year":"2011","journal-title":"Cancer Res."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1460","DOI":"10.1021\/acschembio.7b00055","article-title":"Disclosing the interaction of carbonic anhydrase IX with cullin-associated NEDD8-dissociated protein 1 by molecular modelling and integrated binding measurements","volume":"12","author":"Buonanno","year":"2017","journal-title":"ACS Chem. Biol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"eabj0364","DOI":"10.1126\/sciadv.abj0364","article-title":"Genome-wide synthetic lethal screen unveils novel CAIX-NFS1\/xCT axis as a targetable vulnerability in hypoxic solid tumors","volume":"7","author":"Chafe","year":"2021","journal-title":"Sci. Adv."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"2065","DOI":"10.1002\/ijc.31607","article-title":"An inhibitory antibody targeting carbonic anhydrase XII abrogates chemoresistance and significantly reduces lung metastases in an orthotopic breast cancer model in vivo","volume":"143","author":"Gondi","year":"2018","journal-title":"Int. J. Cancer"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"420","DOI":"10.4149\/neo_2018_180819N624","article-title":"High expression of carbonic anhydrase 12 (CA12) is associated with good prognosis in breast cancer","volume":"66","author":"Li","year":"2019","journal-title":"Neoplasma"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"408","DOI":"10.1016\/j.bbrc.2019.06.040","article-title":"Carbonic anhydrase XII expression is linked to suppression of Sonic hedgehog ligand expression in triple-negative breast cancer cells","volume":"516","author":"Guerrini","year":"2019","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"9799","DOI":"10.1002\/jcp.26947","article-title":"Inhibition of smoothened in breast cancer cells reduces CAXII expression and cell migration","volume":"233","author":"Guerrini","year":"2018","journal-title":"J. Cell. Physiol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1016\/j.tips.2009.03.007","article-title":"Mechanisms of Hedgehog pathway activation in cancer and implications for therapy","volume":"30","author":"Scales","year":"2009","journal-title":"Trends Pharmacol. Sci."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"2454","DOI":"10.1101\/gad.1693608","article-title":"Hedgehog: Functions and mechanisms","volume":"22","author":"Varjosalo","year":"2008","journal-title":"Genes Dev."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Zeng, X., and Ju, D. (2018). Hedgehog signalling pathway and autophagy in cancer. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19082279"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"416","DOI":"10.1038\/nrm3598","article-title":"The mechanisms of hedgehog signalling and its roles in development and disease","volume":"14","author":"Briscoe","year":"2013","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Giuntini, G., Monaci, S., Cau, Y., Mori, M., Naldini, A., and Carraro, F. (2020). Inhibition of Melanoma Cell Migration and Invasion Targeting the Hypoxic Tumor Associated CA XII. Cancers, 12.","DOI":"10.3390\/cancers12103018"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"292","DOI":"10.1021\/jm990479+","article-title":"Carbonic anhydrase inhibitors: Synthesis of membrane-impermeant low molecular weight sulfonamides possessing in vivo selectivity for the membrane-bound versus cytosolic isozymes","volume":"43","author":"Scozzafava","year":"2000","journal-title":"J. Med. Chem."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1005","DOI":"10.1016\/S0960-894X(03)00091-X","article-title":"Carbonic anhydrase inhibitors: Inhibition of the tumor-associated isozyme IX with aromatic and heterocyclic sulfonamides","volume":"13","author":"Vullo","year":"2003","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"561","DOI":"10.1080\/14756366.2021.1882453","article-title":"Reconsidering anion inhibitors in the general context of drug design studies of modulators of activity of the classical enzyme carbonic anhydrase","volume":"36","author":"Nocentini","year":"2021","journal-title":"J. Enzym. Inhib. Med. Chem."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"345","DOI":"10.3109\/14756366.2015.1122001","article-title":"How many carbonic anhydrase inhibition mechanisms exist?","volume":"31","author":"Supuran","year":"2016","journal-title":"J. Enzym. Inhib. Med. Chem."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1080\/17460441.2017.1253677","article-title":"Advances in structure-based drug discovery of carbonic anhydrase inhibitors","volume":"12","author":"Supuran","year":"2017","journal-title":"Expert Opin. Drug Discov."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"759","DOI":"10.3109\/14756366.2012.672983","article-title":"Structure-based drug discovery of carbonic anhydrase inhibitors","volume":"27","author":"Supuran","year":"2012","journal-title":"J. Enzym. Inhib. Med. Chem."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"484","DOI":"10.1097\/COC.0000000000000691","article-title":"A Phase 1 Study of SLC-0111, a Novel Inhibitor of Carbonic Anhydrase IX, in Patients with Advanced Solid Tumors","volume":"43","author":"McDonald","year":"2020","journal-title":"Am. J. Clin. Oncol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"729","DOI":"10.1080\/13543776.2018.1508453","article-title":"Carbonic anhydrase inhibitors as antitumor\/antimetastatic agents: A patent review (2008\u20132018)","volume":"28","author":"Nocentini","year":"2018","journal-title":"Expert Opin. Ther. Pat."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"2569","DOI":"10.1016\/j.bmc.2017.03.027","article-title":"Synthesis and carbonic anhydrase inhibition of a series of SLC-0111 analogs","volume":"25","author":"Carta","year":"2017","journal-title":"Bioorg. Med. Chem."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"6328","DOI":"10.1021\/acs.jmedchem.8b00770","article-title":"Discovery of 4-Hydroxy- 3-(3-(phenylureido)benzenesulfonamides as SLC-0111 analogues for the treatment of hypoxic tumors overexpressing carbonic anhydrase IX","volume":"61","author":"Bozdag","year":"2018","journal-title":"J. Med. Chem."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"10860","DOI":"10.1021\/acs.jmedchem.8b01504","article-title":"4-Hydroxy- 3-nitro-5-ureido-benzenesulfonamides selectively target the tumor-associated carbonic anhydrase isoforms IX and XII showing hypoxia-enhanced antiproliferative profiles","volume":"61","author":"Nocentini","year":"2018","journal-title":"J. Med. Chem."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"549","DOI":"10.1016\/j.bioorg.2018.11.014","article-title":"SLC-0111 enaminone analogs, 3\/4-(3-aryl-3-oxopropenyl) aminobenzenesulfonamides, as novel selective subnanomolar inhibitors of the tumor-associated carbonic anhydrase isoform IX","volume":"83","author":"Eldehna","year":"2018","journal-title":"Bioorg. Chem."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1016\/j.bioorg.2018.10.005","article-title":"Design, synthesis and biological evaluation of novel ureido benzenesulfonamides incorporating 1,3,5-triazine moieties as potent carbonic anhydrase IX inhibitors","volume":"82","author":"Lolak","year":"2018","journal-title":"Bioorg. Chem."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"276","DOI":"10.1016\/j.ejmech.2017.11.061","article-title":"Inhibitory effects and structural insights for a novel series of coumarin-based compounds that selectively target human CA IX and CA XII carbonic anhydrases","volume":"143","author":"Mancuso","year":"2018","journal-title":"Eur. J. Med. Chem."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1578","DOI":"10.1002\/cmdc.201700446","article-title":"Sulfocoumarin-, coumarin-, 4-sulfamoylphenyl-bearing indazole-3-carboxamide hybrids: Synthesis and selective inhibition of tumor-associated carbonic anhydrase isozymes IX and XII","volume":"12","author":"Angapelly","year":"2017","journal-title":"ChemMedChem"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"677","DOI":"10.1016\/j.bmc.2016.11.039","article-title":"Coumarins and other fused bicyclic heterocycles with selective tumor-associated carbonic anhydrase isoforms inhibitory activity","volume":"25","author":"Bozdag","year":"2017","journal-title":"Bioorg. Med. Chem."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1016\/j.ejmech.2018.01.033","article-title":"Structural investigations on coumarins leading to chromeno[4,3-c]pyrazol-4-ones and pyrano[4,3-c]pyrazol-4-ones: New scaffolds for the design of the tumor-associated carbonic anhydrase isoforms IX and XII","volume":"146","author":"Bonardi","year":"2018","journal-title":"Eur. J. Med. Chem."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"2337","DOI":"10.1021\/jm031079w","article-title":"Carbonic Anhydrase Inhibitors. Design of Selective, Membrane-Impermeant Inhibitors Targeting the Human Tumor-Associated Isozyme IX","volume":"47","author":"Casey","year":"2004","journal-title":"J. Med. Chem."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"6539","DOI":"10.1021\/jm060967z","article-title":"A Novel Class of Carbonic Anhydrase Inhibitors: Glycoconjugate Benzene Sulfonamides Prepared by \u201cClick-Tailing\u201d","volume":"49","author":"Wilkinson","year":"2006","journal-title":"J. Med. Chem."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"10692","DOI":"10.1021\/acs.jmedchem.6b01389","article-title":"Benzenesulfonamides Incorporating Flexible Triazole Moieties Are Highly Effective Carbonic Anhydrase Inhibitors: Synthesis and Kinetic, Crystallographic, Computational, and Intraocular Pressure Lowering Investigations","volume":"59","author":"Nocentini","year":"2016","journal-title":"J. Med. Chem."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1226","DOI":"10.3109\/14756366.2015.1115401","article-title":"7-Aryl-triazolyl-substituted sulfocoumarins are potent, selective inhibitors of the tumor-associated carbonic anhydrase IX and XII","volume":"31","author":"Nocentini","year":"2016","journal-title":"J. Enzym. Inhib. Med. Chem."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"6955","DOI":"10.1016\/j.bmc.2015.09.041","article-title":"Click-tailed coumarins with potent and selective inhibitory action against the tumor-associated carbonic anhydrases IX and XII","volume":"23","author":"Nocentini","year":"2015","journal-title":"Bioorg. Med. Chem."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"7392","DOI":"10.1021\/acs.jmedchem.0c00636","article-title":"Azidothymidine \u201cClicked\u201d into 1,2,3-Triazoles: First Report on Carbonic Anhydrase-Telomerase Dual-Hybrid Inhibitors","volume":"63","author":"Berrino","year":"2020","journal-title":"J. Med. Chem."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1016\/j.ejmech.2020.112112","article-title":"Inclusion of a 5-fluorouracil moiety in nitrogenous bases derivatives as human carbonic anhydrase IX and XII inhibitors produced a targeted action against MDA-MB-231 and T47D breast cancer cells","volume":"190","author":"Petreni","year":"2020","journal-title":"Eur. J. Med. Chem."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1314","DOI":"10.1021\/acsmedchemlett.7b00399","article-title":"Discovery of New Sulfonamide Carbonic Anhydrase IX Inhibitors Incorporating Nitrogenous Bases","volume":"8","author":"Nocentini","year":"2017","journal-title":"ACS Med. Chem. Lett."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"2561","DOI":"10.1016\/S0021-9258(18)62326-9","article-title":"The carbon dioxide hydration activity of carbonic anhydrase. I. Stop-flow kinetic studies on the native human isoenzymes B and C","volume":"246","author":"Khalifah","year":"1971","journal-title":"J. Biol. Chem."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"618","DOI":"10.1016\/j.jphotobiol.2017.06.031","article-title":"Pharmacological activities of an eye drop containing Matricaria chamomilla and Euphrasia officinalis extracts in UVB-induced oxidative stress and inflammation of human corneal cells","volume":"173","author":"Bigagli","year":"2017","journal-title":"J. Photochem. Photobiol. B"},{"key":"ref_60","unstructured":"ICH Quality Guidelines Q2 (R1). Validation of Analytical Procedures: Text and Methodology. Proceedings of the International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use, Available online: https:\/\/database.ich.org\/sites\/default\/files\/Q2%28R1%29%20Guideline.pdf."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/1\/461\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T07:56:59Z","timestamp":1760169419000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/1\/461"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,12,31]]},"references-count":60,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2022,1]]}},"alternative-id":["ijms23010461"],"URL":"https:\/\/doi.org\/10.3390\/ijms23010461","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,12,31]]}}}