State of the art of carbonic anhydrase activators

Future Medicinal ChemistryVol. 15, No. 22 EditorialState of the art of carbonic anhydrase activatorsFrancesco Fiorentino, Fabrizio Carta, Dante Rotili, Antonello Mai & Claudiu T SupuranFrancesco Fiorentino https://orcid.org/0000-0003-3550-1860Department of Drug Chemistry & Technologies, Sapienza University of Rome, Piazzale Aldo Moro 5, Rome, 00185, ItalySearch for more papers by this author, Fabrizio Carta *Author for correspondence: E-mail Address: fabrizio.carta@unifi.ithttps://orcid.org/0000-0002-1141-6146Department of Neurofarba, Section of Pharmaceutical & Nutraceutical Sciences, Polo Scientifico, University of Florence, Via U Schiff 6, Firenze, Sesto Fiorentino, 50019, ItalySearch for more papers by this author, Dante Rotili **Author for correspondence: E-mail Address: dante.rotili@uniroma1.ithttps://orcid.org/0000-0002-8428-8763Department of Drug Chemistry & Technologies, Sapienza University of Rome, Piazzale Aldo Moro 5, Rome, 00185, ItalySearch for more papers by this author, Antonello Mai https://orcid.org/0000-0001-9176-2382Department of Drug Chemistry & Technologies, Sapienza University of Rome, Piazzale Aldo Moro 5, Rome, 00185, ItalyPasteur Institute, Cenci-Bolognetti Foundation, Sapienza University of Rome, Piazzale Aldo Moro 5, Rome, 00185, ItalySearch for more papers by this author & Claudiu T Supuran https://orcid.org/0000-0003-4262-0323Department of Neurofarba, Section of Pharmaceutical & Nutraceutical Sciences, Polo Scientifico, University of Florence, Via U Schiff 6, Firenze, Sesto Fiorentino, 50019, ItalySearch for more papers by this authorPublished Online:10 Oct 2023https://doi.org/10.4155/fmc-2023-0193AboutSectionsView ArticleView Full TextPDF/EPUB ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareShare onFacebookTwitterLinkedInRedditEmail View articleKeywords: carbonic anhydrase activatorscarbonic anhydrasescognition-related disordershistaminepharmacological applicationsReferences1. Supuran CT. Emerging role of carbonic anhydrase inhibitors. Clin. Sci. (Lond.) 10, 1233–1249 (2021).Crossref, Google Scholar2. Supuran CT. Carbonic anhydrases: novel therapeutic applications for inhibitors and activators. Nat. Rev. Drug Discov. 2, 168–181 (2008).Crossref, Google Scholar3. Supuran CT. Exploring the multiple binding modes of inhibitors to carbonic anhydrases for novel drug discovery. Expert Opin. Drug Discov. 6, 671–686 (2020).Crossref, Google Scholar4. Chafe SC, Vizeacoumar FS, Venkateswaran G et al. Genome-wide synthetic lethal screen unveils novel CAIX-NFS1/xCT axis as a targetable vulnerability in hypoxic solid tumors. Sci. Adv. 35, eabj0364 (2021).Crossref, Google Scholar5. Leiner M, Leiner G. Die aktivatoren der kohlensäureanhydratase. Sci. Nat. 13, 195–197 (1941).Crossref, Google Scholar6. Main RE, Locke A. Activation of carbonic anhydrase by histamine. J. Biol. Chem. 140, LXXXI (1941).Crossref, Google Scholar7. Briganti F, Mangani S, Orioli P, Scozzafava A, Vernaglione G, Supuran CT. Carbonic anhydrase activators: x-ray crystallographic and spectroscopic investigations for the interaction of isozymes I and II with histamine. Biochemistry 36(34), 10384–10392 (1997).Crossref, Medline, CAS, Google Scholar8. Akocak S, Supuran CT. Activation of α-, β-, γ- δ-, ζ- and η- class of carbonic anhydrases with amines and amino acids: a review. J. Enzyme Inhib. Med. Chem. 1, 1652–1659 (2019).Crossref, Google Scholar9. Saada MC, Vullo D, Montero JL, Scozzafava A, Supuran CT, Winum J-Y. Mono- and di-halogenated histamine, histidine and carnosine derivatives are potent carbonic anhydrase I, II, VII, XII and XIV activators. Bioorg. Med. Chem. 17, 4752–4758 (2014).Crossref, Google Scholar10. Saada MC, Montero JL, Vullo D, Scozzafava A, Winum J-Y, Supuran CT. Carbonic anhydrase activators: gold nanoparticles coated with derivatized histamine, histidine, and carnosine show enhanced activatory effects on several mammalian isoforms. J. Med. Chem. 5, 1170–1177 (2011).Crossref, Google Scholar11. Angeli A, Vaiano F, Mari F, Bertol E, Supuran CT. Psychoactive substances belonging to the amphetamine class potently activate brain carbonic anhydrase isoforms VA, VB, VII, and XII. J. Enzyme Inhib. Med. Chem. 1, 1253–1259 (2017).Crossref, Google Scholar12. Sugimoto A, Ikeda H, Tsukamoto H et al. Timolol activates the enzyme activities of human carbonic anhydrase I and II. Biol. Pharm. Bull. 2, 301–306 (2010).Crossref, Google Scholar13. Coban TA, Beydemir S, Gülcin I et al. Sildenafil is a strong activator of mammalian carbonic anhydrase isoforms I–XIV. Bioorg. Med. Chem. 16, 5791–5795 (2009).Crossref, Google Scholar14. Provensi G, Nocentini A, Passani MB, Blandina P, Supuran CT. Activation of carbonic anhydrase isoforms involved in modulation of emotional memory and cognitive disorders with histamine agonists, antagonists and derivatives. J. Enzyme Inhib. Med. Chem. 1, 719–726 (2021).Crossref, Google Scholar15. Casini A, Caccia S, Scozzafava A, Supuran CT. Carbonic anhydrase activators. The selective serotonin reuptake inhibitors fluoxetine, sertraline and citalopram are strong activators of isozymes I and II. Bioorg. Med. Chem. Lett. 16, 2765–2768 (2003).Crossref, Google Scholar16. Fiorentino F, Nocentini A, Rotili D, Supuran CT, Mai A. Antihistamines, phenothiazine-based antipsychotics, and tricyclic antidepressants potently activate pharmacologically relevant human carbonic anhydrase isoforms II and VII. J. Enzyme Inhib. Med. Chem. 1, 2188147 (2023).Crossref, Google Scholar17. Schmidt SD, Costa A, Rani B et al. The role of carbonic anhydrases in extinction of contextual fear memory. Proc. Natl Acad. Sci. USA 117(27), 16000–16008 (2020).Crossref, Medline, Google Scholar18. Meier-Ruge W, Iwangoff P, Reichlmeier K. Neurochemical enzyme changes in Alzheimer's and Pick's disease. Arch. Gerontol. Geriatr. 2, 161–165 (1984).Crossref, Google Scholar19. Müller WEG, Schröder HC, Schlossmacher U, Grebenjuk VA, Ushijima H, Wang X. Induction of carbonic anhydrase in SaOS-2 cells, exposed to bicarbonate and consequences for calcium phosphate crystal formation. Biomaterials 34, 8671–8680 (2013).Crossref, Medline, CAS, Google Scholar20. Wang X, Schröder HC, Schlossmacher U et al. Modulation of the initial mineralization process of SaOS-2 cells by carbonic anhydrase activators and polyphosphate. Calcif. Tissue Int. 5, 495–509 (2014).Crossref, Google ScholarFiguresReferencesRelatedDetails Vol. 15, No. 22 STAY CONNECTED Metrics Downloaded 26 times History Received 3 July 2023 Accepted 11 September 2023 Published online 10 October 2023 Published in print November 2023 Information© 2023 Newlands PressKeywordscarbonic anhydrase activatorscarbonic anhydrasescognition-related disordershistaminepharmacological applicationsDisclaimerThe views and opinions expressed in this manuscript are those of the authors only and do not necessarily reflect those of the EU or European Commission.Financial disclosureThe research leading to some of the results reported in this work was supported by the Italian Ministry of Education, University and Research via the MeDyCa grant (FISR2019_00374) (A Mai) and NextGenerationEU under HEAL ITALIA (PNRR M4C2-I1.3 Project PE_00000019) (D Rotili) CUP B53C22004000006. CT Supuran thanks the Italian Ministry of Education, University and Research for a PRIN grant (2017XYBP2R) and Ente Cassa di Risparmio di Firenze grant (CRF2020.1395). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.Competing interests disclosureThe authors have no competing interests or relevant affiliations with any organization or entity with an interest in or conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending or royalties.Writing disclosureNo writing assistance was utilized in the production of this manuscript.PDF download