{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T13:01:31Z","timestamp":1777640491844,"version":"3.51.4"},"reference-count":33,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2016,12,15]],"date-time":"2016-12-15T00:00:00Z","timestamp":1481760000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Natural products represent a straightforward source for molecular structures bearing a vast array of chemical features and potentially useful for biomedical purposes. Recent examples of this type include the discovery of the coumarins and the polyamine natural products as atypical chemotypes for the inhibition of the metalloenzymes carbonic anhydrases (CAs; EC 4.2.2.1). CA enzymes are established pharmacological targets for important pathologies, which, among others, include glaucoma, hypoxic tumors, and central nervous system (CNS)-affecting diseases. Moreover, they are expressed in many bacteria, fungi and helminths which are the etiological agents of the majority of infectious diseases. In this context, natural products represent the ideal source of new and selective druggable CA modulators for biomedical purposes. Herein we report the state of the art on polyamines of natural origin as well as of synthetic derivatives as inhibitors of human CAs.<\/jats:p>","DOI":"10.3390\/molecules21121726","type":"journal-article","created":{"date-parts":[[2016,12,15]],"date-time":"2016-12-15T10:53:16Z","timestamp":1481799196000},"page":"1726","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Polyamines and \u03b1-Carbonic Anhydrases"],"prefix":"10.3390","volume":"21","author":[{"given":"Andrea","family":"Scozzafava","sequence":"first","affiliation":[{"name":"Laboratorio di Chimica Bioinorganica, Universit\u00e0 degli Studi di Firenze, Rm. 188, Via della Lastruccia 3, 50019 Sesto Fiorentino, Florence, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4262-0323","authenticated-orcid":false,"given":"Claudiu","family":"Supuran","sequence":"additional","affiliation":[{"name":"NEUROFARBA Department, University of Florence, Sezione di Scienze Farmaceutiche, Via Ugo Schiff 6, 50019 Sesto Fiorentino, Florence, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1141-6146","authenticated-orcid":false,"given":"Fabrizio","family":"Carta","sequence":"additional","affiliation":[{"name":"NEUROFARBA Department, University of Florence, Sezione di Scienze Farmaceutiche, Via Ugo Schiff 6, 50019 Sesto Fiorentino, Florence, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2016,12,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1093\/aob\/mcp259","article-title":"Polyamines: Ubiquitous polycations with unique roles in growth and stress responses","volume":"105","author":"Takahashi","year":"2010","journal-title":"Ann. Bot."},{"key":"ref_2","first-page":"1","article-title":"Polyamines in plants: An overview","volume":"2","author":"Tiburcio","year":"2003","journal-title":"J. Cell. Mol. Biol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1007\/BF03191144","article-title":"Regulatory Mechanisms of Polyamine Biosynthesis in Plants","volume":"31","author":"Carbonell","year":"2009","journal-title":"Genes Genom."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"393","DOI":"10.1007\/s00726-009-0396-7","article-title":"Polyamines: Fundamental characters in chemistry and biology","volume":"38","author":"Agostinelli","year":"2010","journal-title":"Amino Acids"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1038\/nrd2243","article-title":"Targeting polyamine metabolism and function in cancer and other hyperproliferative diseases","volume":"6","author":"Casero","year":"2007","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"2119","DOI":"10.1093\/molbev\/msn161","article-title":"Evolutionary diversification in polyamine biosynthesis","volume":"25","author":"Minguet","year":"2008","journal-title":"Mol. Biol. Evol."},{"key":"ref_7","first-page":"87","article-title":"Polyamines: Emerging players in bacteria-host interactions","volume":"13","author":"Campilongo","year":"2013","journal-title":"Int. J. Med. Microbiol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1146\/annurev.pa.35.040195.000415","article-title":"Polyamines as targets for therapeutic intervention","volume":"35","author":"Marton","year":"1995","journal-title":"Annu. Rev. Pharmacol. Toxicol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"42041","DOI":"10.1074\/jbc.M406053200","article-title":"Structural analysis of DNA interactions with biogenic polyamines and cobalt(III)hexamine studied by Fourier transform infrared and capillary electrophoresis","volume":"279","author":"Ouameur","year":"2004","journal-title":"J. Biol. Chem."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"5511","DOI":"10.1021\/jm1003667","article-title":"Polyamines inhibit carbonic anhydrases by anchoring to the zinc-coordinated water molecule","volume":"53","author":"Carta","year":"2010","journal-title":"J. Med. Chem."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"374079","DOI":"10.1155\/2014\/374079","article-title":"Natural product polyamines that inhibit human carbonic anhydrases","volume":"2014","author":"Davis","year":"2014","journal-title":"BioMed Res. Int."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1016\/0968-0004(90)90216-X","article-title":"Molecular genetics of polyamine synthesis in eukaryotic cells","volume":"15","author":"Heby","year":"1990","journal-title":"Trends Biochem. Sci."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"485","DOI":"10.3892\/ijo_00000360","article-title":"Cytotoxicity of spermine oxidation products to multidrug resistant melanoma cells (M14 ADR2): Sensitization by MDL 72527, a lysosomotropic compound","volume":"35","author":"Agostinelli","year":"2009","journal-title":"Int. J. Oncol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1042\/BST0350295","article-title":"Polyamines and neoplastic growth","volume":"35","author":"Pegg","year":"2007","journal-title":"Biochem. Soc. Trans."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"2349","DOI":"10.2174\/0929867043364559","article-title":"Interaction of biologically active amines with mitochondria and their role in the mitochondrial-mediated pathway of apoptosis","volume":"11","author":"Toninello","year":"2004","journal-title":"Curr. Med. Chem."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Supuran, C.T., and Winum, J.Y. (2009). Drug Design of Zinc-Enzyme Inhibitors: Functional, Structural, and Disease Applications, Wiley.","DOI":"10.1002\/9780470508169"},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Chegwidden, W.R., Carter, N., and Edwards, Y. (2000). The Carbonic Anhydrases: New Horizons, Birkhauser Verlag.","DOI":"10.1007\/978-3-0348-8446-4"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"3019","DOI":"10.1021\/jm0603320","article-title":"Carbonic anhydrase activators. Activation of isoforms I, II, IV, VA, VII, and XIV with l- and d-phenylalanine and crystallographic analysis of their adducts with isozyme II: Stereospecific recognition within the active site of an enzyme and its consequences for the drug design","volume":"49","author":"Temperini","year":"2006","journal-title":"J. Med. Chem."},{"key":"ref_19","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_20","doi-asserted-by":"crossref","first-page":"5980","DOI":"10.1039\/C4CC02346C","article-title":"Ethylene bis-imidazoles are highly potent and selective activators for isozymes VA and VII of carbonic anhydrase, with a potential nootropic effect","volume":"50","author":"Draghici","year":"2014","journal-title":"Chem. Commun."},{"key":"ref_21","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_22","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1107\/S2052252514004096","article-title":"Structural insight into activity enhancement and inhibition of H64A carbonic anhydrase II by imidazoles","volume":"1","author":"Aggarwal","year":"2014","journal-title":"IUCrJ"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1021\/bi902007b","article-title":"A short, strong hydrogen bond in the active site of human carbonic anhydrase II","volume":"49","author":"Avvaru","year":"2010","journal-title":"Biochemistry"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1001","DOI":"10.1021\/np300147d","article-title":"Ianthelliformisamines AC, antibacterial bromotyrosine-derived metabolites from the marine sponge Suberea ianthelliformis","volume":"5","author":"Xu","year":"2012","journal-title":"J. Nat. Prod."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1746","DOI":"10.1021\/np0702483","article-title":"Citromycetins and bilains A\u2013C: New aromatic polyketides and diketopiperazines from Australian marine-derived and terrestrial Penicillium spp.","volume":"11","author":"Capon","year":"2007","journal-title":"J. Nat. Prod."},{"key":"ref_26","first-page":"312","article-title":"Pistillarin salt, a dicatecholspermidine family member from Gomphus floccosus, inhibits DNA single strand breakage by the fenton reaction","volume":"2","author":"Lee","year":"2011","journal-title":"J. Korean Soc. Appl. Biol. Chem."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1515\/znc-1984-1-202","article-title":"Pistillarin, a characteristic metabolite of Clavariadelphus pistillaris and several Ramaria species (Basidiomycetes)","volume":"39","author":"Steglich","year":"1984","journal-title":"Z. Naturforsch. C"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"5188","DOI":"10.1016\/j.tetlet.2013.07.058","article-title":"The discovery, synthesis and antimalarial evaluation of natural product-based polyamine alkaloids","volume":"54","author":"Choomuenwai","year":"2013","journal-title":"Tetrahedron Lett."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"6860","DOI":"10.1016\/j.bmcl.2007.10.021","article-title":"Spermatinamine, the first natural product inhibitor of isoprenylcysteine carboxyl methyltransferase, a new cancer target","volume":"24","author":"Buchanan","year":"2007","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"ref_30","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_31","doi-asserted-by":"crossref","first-page":"3057","DOI":"10.1021\/ja809683v","article-title":"Non-zinc mediated inhibition of carbonic anhydrases: Coumarins are a new class of suicide inhibitors","volume":"131","author":"Maresca","year":"2009","journal-title":"J. Am. Chem. Soc."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1021\/jm901287j","article-title":"Deciphering the mechanism of carbonic anhydrase inhibition with coumarins and thiocoumarins","volume":"53","author":"Maresca","year":"2010","journal-title":"J. Med. Chem."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"3659","DOI":"10.1021\/ja00087a086","article-title":"Phenol as a carbonic anhydrase inhibitor","volume":"116","author":"Nair","year":"1994","journal-title":"J. Am. Chem. Soc."}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/21\/12\/1726\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T19:28:39Z","timestamp":1760210919000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/21\/12\/1726"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,12,15]]},"references-count":33,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2016,12]]}},"alternative-id":["molecules21121726"],"URL":"https:\/\/doi.org\/10.3390\/molecules21121726","relation":{},"ISSN":["1420-3049"],"issn-type":[{"value":"1420-3049","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,12,15]]}}}