{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T21:20:27Z","timestamp":1792185627656,"version":"4.4.0"},"reference-count":52,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2018,11,8]],"date-time":"2018-11-08T00:00:00Z","timestamp":1541635200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003125","name":"Suomen Kulttuurirahasto","doi-asserted-by":"publisher","award":["None"],"award-info":[{"award-number":["None"]}],"id":[{"id":"10.13039\/501100003125","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100006706","name":"Tampereen Tuberkuloosis\u00e4\u00e4ti\u00f6","doi-asserted-by":"publisher","award":["None"],"award-info":[{"award-number":["None"]}],"id":[{"id":"10.13039\/501100006706","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004012","name":"Jane ja Aatos Erkon S\u00e4\u00e4ti\u00f6","doi-asserted-by":"publisher","award":["None"],"award-info":[{"award-number":["None"]}],"id":[{"id":"10.13039\/501100004012","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Mycobacteria cause a variety of diseases, such as tuberculosis, leprosy, and opportunistic diseases in immunocompromised people. The treatment of these diseases is problematic, necessitating the development of novel treatment strategies. Recently, \u03b2-carbonic anhydrases (\u03b2-CAs) have emerged as potential drug targets in mycobacteria. The genomes of mycobacteria encode for three \u03b2-CAs that have been cloned and characterized from Mycobacterium tuberculosis (Mtb) and the crystal structures of two of the enzymes have been determined. Different classes of inhibitor molecules against Mtb \u03b2-CAs have subsequently been designed and have been shown to inhibit these mycobacterial enzymes in vitro. The inhibition of these centrally important mycobacterial enzymes leads to reduced growth of mycobacteria, lower virulence, and impaired biofilm formation. Thus, the inhibition of \u03b2-CAs could be a novel approach for developing drugs against the severe diseases caused by pathogenic mycobacteria. In the present article, we review the data related to in vitro and in vivo inhibition studies in the field.<\/jats:p>","DOI":"10.3390\/molecules23112911","type":"journal-article","created":{"date-parts":[[2018,11,9]],"date-time":"2018-11-09T03:08:02Z","timestamp":1541732882000},"page":"2911","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":40,"title":["Carbonic Anhydrase Inhibitors as Novel Drugs against Mycobacterial \u03b2-Carbonic Anhydrases: An Update on In Vitro and In Vivo Studies"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6938-7835","authenticated-orcid":false,"given":"Ashok","family":"Aspatwar","sequence":"first","affiliation":[{"name":"Faculty of Medicine and Health Technology, University of Tampere, 33014 Tampere, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3197-3414","authenticated-orcid":false,"given":"Jean-Yves","family":"Winum","sequence":"additional","affiliation":[{"name":"Institut des Biomol\u00e9cules Max Mousseron (IBMM) UMR 5247 CNRS, ENSCM, Universit\u00e9 de Montpellier, 34296 Montpellier CEDEX 05, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1141-6146","authenticated-orcid":false,"given":"Fabrizio","family":"Carta","sequence":"additional","affiliation":[{"name":"Neurofarba Department, Sezione di Chimica Farmaceutica e Nutraceutica, Universit\u00e0 degli Studi di Firenze, 50019 Sesto Fiorentino (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, Sezione di Chimica Farmaceutica e Nutraceutica, Universit\u00e0 degli Studi di Firenze, 50019 Sesto Fiorentino (Firenze), Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9076-8782","authenticated-orcid":false,"given":"Milka","family":"Hammaren","sequence":"additional","affiliation":[{"name":"Faculty of Medicine and Health Technology, University of Tampere, 33014 Tampere, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mataleena","family":"Parikka","sequence":"additional","affiliation":[{"name":"Faculty of Medicine and Health Technology, University of Tampere, 33014 Tampere, Finland"},{"name":"Oral and Maxillofacial Unit, Tampere University Hospital, 33521 Tampere, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7323-8536","authenticated-orcid":false,"given":"Seppo","family":"Parkkila","sequence":"additional","affiliation":[{"name":"Faculty of Medicine and Health Technology, University of Tampere, 33014 Tampere, Finland"},{"name":"Fimlab Ltd. and Tampere University Hospital, 33520 Tampere, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2018,11,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1128\/jb.172.1.116-124.1990","article-title":"The division between fast- and slow-growing species corresponds to natural relationships among the mycobacteria","volume":"172","author":"Stahl","year":"1990","journal-title":"J. Bacteriol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1016\/j.diagmicrobio.2012.09.019","article-title":"Differentiating rapid- and slow-growing mycobacteria by difference in time to growth detection in liquid media","volume":"75","author":"Kim","year":"2013","journal-title":"Diagn. Microbiol. Infect. Dis."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Sinha, P., Gupta, A., Prakash, P., Anupurba, S., Tripathi, R., and Srivastava, G.N. (2016). Differentiation of Mycobacterium tuberculosis complex from non-tubercular mycobacteria by nested multiplex PCR targeting IS6110, MTP40 and 32kD alpha antigen encoding gene fragments. BMC Infect. Dis., 16.","DOI":"10.1186\/s12879-016-1450-1"},{"key":"ref_4","unstructured":"WHO (2018). Global Tuberculosis Report 2018, World Health Organization."},{"key":"ref_5","unstructured":"WHO (2017). World Health Organization Lepracy: Fact Sheet on Leprosy, World Health Organization."},{"key":"ref_6","first-page":"665","article-title":"Pulmonary non-tuberculous mycobacterial infections","volume":"14","author":"Daley","year":"2010","journal-title":"Int. J. Tuberc. Lung Dis."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1007\/s00284-010-9706-2","article-title":"Prevalence and concentration of non-tuberculous mycobacteria in cooling towers by means of quantitative PCR: A prospective study","volume":"62","author":"Adrados","year":"2011","journal-title":"Curr. Microbiol."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"King, H.C., Khera-Butler, T., James, P., Oakley, B.B., Erenso, G., Aseffa, A., Knight, R., Wellington, E.M., and Courtenay, O. (2017). Environmental reservoirs of pathogenic mycobacteria across the Ethiopian biogeographical landscape. PLoS ONE, 12.","DOI":"10.1371\/journal.pone.0173811"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1055\/s-0033-1333568","article-title":"Ecology of nontuberculous mycobacteria--where do human infections come from?","volume":"34","author":"Falkinham","year":"2013","journal-title":"Semin. Respir. Crit. Care Med."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Gopinath, K., and Singh, S. (2010). Non-tuberculous mycobacteria in TB-endemic countries: Are we neglecting the danger?. PLoS Negl. Trop. Dis., 4.","DOI":"10.1371\/journal.pntd.0000615"},{"key":"ref_11","first-page":"210","article-title":"Nontuberculous mycobacterial pulmonary infections","volume":"6","author":"Johnson","year":"2014","journal-title":"J. Thorac. Dis."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Faria, S., Joao, I., and Jordao, L. (2015). General Overview on Nontuberculous Mycobacteria, Biofilms, and Human Infection. J. Pathog., 809014.","DOI":"10.1155\/2015\/809014"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1007\/s11908-018-0611-3","article-title":"Skin and Soft Tissue Infections Due to Nontuberculous Mycobacteria","volume":"20","author":"Misch","year":"2018","journal-title":"Curr. Infect. Dis. Rep."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Al-Ghafli, H., and Al-Hajoj, S. (2017). Nontuberculous Mycobacteria in Saudi Arabia and Gulf Countries: A Review. Can. Respir. J., 5035932.","DOI":"10.1155\/2017\/5035932"},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Nishiuchi, Y., Iwamoto, T., and Maruyama, F. (2017). Infection Sources of a Common Non-tuberculous Mycobacterial Pathogen, Mycobacterium avium Complex. Front. Med., 27.","DOI":"10.3389\/fmed.2017.00027"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"45258","DOI":"10.1038\/srep45258","article-title":"Genomic characterization of Nontuberculous Mycobacteria","volume":"7","author":"Fedrizzi","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"729","DOI":"10.1101\/gr.075069.107","article-title":"Insights from the complete genome sequence of Mycobacterium marinum on the evolution of Mycobacterium tuberculosis","volume":"18","author":"Stinear","year":"2008","journal-title":"Genome Res."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"537","DOI":"10.1038\/31159","article-title":"Deciphering the biology of Mycobacterium tuberculosis from the complete genome sequence","volume":"393","author":"Cole","year":"1998","journal-title":"Nature"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"Reviews1023","DOI":"10.1186\/gb-2001-2-8-reviews1023","article-title":"The genome of Mycobacterium leprae: A minimal mycobacterial gene set","volume":"2","author":"Vissa","year":"2001","journal-title":"Genome Biol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1007","DOI":"10.1038\/35059006","article-title":"Massive gene decay in the leprosy bacillus","volume":"409","author":"Cole","year":"2001","journal-title":"Nature"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"S3","DOI":"10.1016\/S1472-9792(08)70032-5","article-title":"A roadmap for drug discovery and its translation to small molecule agents in clinical development for tuberculosis treatment","volume":"88","author":"Showalter","year":"2008","journal-title":"Tuberculosis"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"18782","DOI":"10.1074\/jbc.M414348200","article-title":"Structure and function of carbonic anhydrases from Mycobacterium tuberculosis","volume":"280","author":"Covarrubias","year":"2005","journal-title":"J. Biol. Chem."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"4993","DOI":"10.1074\/jbc.M510756200","article-title":"Structural mechanics of the pH-dependent activity of beta-carbonic anhydrase from Mycobacterium tuberculosis","volume":"281","author":"Covarrubias","year":"2006","journal-title":"J. Biol. Chem."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"169","DOI":"10.2174\/187152108784911232","article-title":"Targeting bacterial metalloenzymes: A new strategy for the development of anti-infective agents","volume":"7","author":"Winum","year":"2008","journal-title":"Anti-Infect. Agents Med. Chem."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1016\/j.tube.2010.09.006","article-title":"The MycoBrowser portal: A comprehensive and manually annotated resource for mycobacterial genomes","volume":"91","author":"Kapopoulou","year":"2011","journal-title":"Tuberculosis"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"832","DOI":"10.1080\/14756366.2017.1332056","article-title":"beta-CA-specific inhibitor dithiocarbamate Fc14-584B: A novel antimycobacterial agent with potential to treat drug-resistant tuberculosis","volume":"32","author":"Aspatwar","year":"2017","journal-title":"J. Enzyme Inhib. Med. Chem."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"2226","DOI":"10.1021\/jm9000488","article-title":"Molecular cloning, characterization, and inhibition studies of the Rv1284 beta-carbonic anhydrase from Mycobacterium tuberculosis with sulfonamides and a sulfamate","volume":"52","author":"Minakuchi","year":"2009","journal-title":"J. Med. Chem."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"3116","DOI":"10.1021\/jm9003126","article-title":"Carbonic anhydrase inhibitors. Cloning, characterization, and inhibition studies of a new beta-carbonic anhydrase from Mycobacterium tuberculosis","volume":"52","author":"Nishimori","year":"2009","journal-title":"J. Med. Chem."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"6649","DOI":"10.1016\/j.bmcl.2009.10.009","article-title":"Carbonic anhydrase inhibitors. Characterization and inhibition studies of the most active beta-carbonic anhydrase from Mycobacterium tuberculosis, Rv3588c","volume":"19","author":"Carta","year":"2009","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"2117","DOI":"10.1021\/jm0512600","article-title":"Carbonic anhydrase inhibitors: DNA cloning and inhibition studies of the alpha-carbonic anhydrase from Helicobacter pylori, a new target for developing sulfonamide and sulfamate gastric drugs","volume":"49","author":"Nishimori","year":"2006","journal-title":"J. Med. Chem."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Supuran, C.T. (2008). Carbonic anhydrases: Novel therapeutic applications for inhibitors and activators. Nat. Rev. Drug Discov., 168\u2013181.","DOI":"10.1038\/nrd2467"},{"key":"ref_32","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_33","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1046\/j.1365-2958.2003.03425.x","article-title":"Genes required for mycobacterial growth defined by high density mutagenesis","volume":"48","author":"Sassetti","year":"2003","journal-title":"Mol. Microbiol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"12989","DOI":"10.1073\/pnas.2134250100","article-title":"Genetic requirements for mycobacterial survival during infection","volume":"100","author":"Sassetti","year":"2003","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"e01597-16","DOI":"10.1128\/mBio.01597-16","article-title":"Identification of Bicarbonate as a Trigger and Genes Involved with Extracellular DNA Export in Mycobacterial Biofilms","volume":"7","author":"Rose","year":"2016","journal-title":"MBio"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"4436","DOI":"10.1128\/AAC.00719-15","article-title":"The Carbonic Anhydrase Inhibitor Ethoxzolamide Inhibits the Mycobacterium tuberculosis PhoPR Regulon and Esx-1 Secretion and Attenuates Virulence","volume":"59","author":"Johnson","year":"2015","journal-title":"Antimicrob Agents Chemother."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"3300","DOI":"10.2174\/138161210793429814","article-title":"The beta-carbonic anhydrases from Mycobacterium tuberculosis as drug targets","volume":"16","author":"Nishimori","year":"2010","journal-title":"Curr. Pharm. Des."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"4063","DOI":"10.1021\/jm9004016","article-title":"Discovery of low nanomolar and subnanomolar inhibitors of the mycobacterial beta-carbonic anhydrases Rv1284 and Rv3273","volume":"52","author":"Maresca","year":"2009","journal-title":"J. Med. Chem."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"4929","DOI":"10.1016\/j.bmcl.2009.07.088","article-title":"Carbonic anhydrase inhibitors. Inhibition of the Rv1284 and Rv3273 beta-carbonic anhydrases from Mycobacterium tuberculosis with diazenylbenzenesulfonamides","volume":"19","author":"Maresca","year":"2009","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"7093","DOI":"10.1016\/j.bmc.2009.09.003","article-title":"Carbonic anhydrase inhibitors. Diazenylbenzenesulfonamides are potent and selective inhibitors of the tumor-associated isozymes IX and XII over the cytosolic isoforms I and II","volume":"17","author":"Carta","year":"2009","journal-title":"Bioorg. Med. Chem."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1016\/j.bmcl.2010.11.064","article-title":"Inhibition of beta-carbonic anhydrases with ureido-substituted benzenesulfonamides","volume":"21","author":"Pacchiano","year":"2011","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"384","DOI":"10.3109\/14756366.2011.645539","article-title":"Dihalogenated sulfanilamides and benzolamides are effective inhibitors of the three beta-class carbonic anhydrases from Mycobacterium tuberculosis","volume":"28","author":"Maresca","year":"2013","journal-title":"J. Enzym. Inhib. Med. Chem."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"686","DOI":"10.3109\/14756366.2013.842233","article-title":"Sulfonamides incorporating fluorine and 1,3,5-triazine moieties are effective inhibitors of three beta-class carbonic anhydrases from Mycobacterium tuberculosis","volume":"29","author":"Ceruso","year":"2014","journal-title":"J. Enzym. Inhib. Med. Chem."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"962","DOI":"10.1080\/14756366.2018.1471475","article-title":"Evaluation of sulphonamide derivatives acting as inhibitors of human carbonic anhydrase isoforms I, II and Mycobacterium tuberculosis beta-class enzyme Rv3273","volume":"33","author":"Wani","year":"2018","journal-title":"J. Enzym. Inhib. Med. Chem."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"407","DOI":"10.3109\/14756366.2011.641015","article-title":"Dithiocarbamates strongly inhibit the beta-class carbonic anhydrases from Mycobacterium tuberculosis","volume":"28","author":"Maresca","year":"2013","journal-title":"J. Enzym. Inhib. Med. Chem."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1682","DOI":"10.1021\/jm1013242","article-title":"Natural product-based phenols as novel probes for mycobacterial and fungal carbonic anhydrases","volume":"54","author":"Davis","year":"2011","journal-title":"J. Med. Chem."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"8322","DOI":"10.1039\/C6OB01477A","article-title":"Mycobacterial carbonic anhydrase inhibition with phenolic acids and esters: Kinetic and computational investigations","volume":"14","author":"Cau","year":"2016","journal-title":"Org. Biomol. Chem."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"740","DOI":"10.1016\/j.bmcl.2012.11.085","article-title":"Inhibition of the beta-carbonic anhydrases from Mycobacterium tuberculosis with C-cinnamoyl glycosides: Identification of the first inhibitor with anti-mycobacterial activity","volume":"23","author":"Buchieri","year":"2013","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"392","DOI":"10.3109\/14756366.2011.650168","article-title":"Inhibition of the beta-class carbonic anhydrases from Mycobacterium tuberculosis with carboxylic acids","volume":"28","author":"Maresca","year":"2013","journal-title":"J. Enzym. Inhib. Med. Chem."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1675","DOI":"10.1016\/S0960-894X(01)00266-9","article-title":"Antimycobacterial activity of 9-sulfonylated\/sulfenylated-6-mercaptopurine derivatives","volume":"11","author":"Scozzafava","year":"2001","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Rose, S.J., Babrak, L.M., and Bermudez, L.E. (2015). Mycobacterium avium Possesses Extracellular DNA that Contributes to Biofilm Formation, Structural Integrity, and Tolerance to Antibiotics. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0128772"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1016\/j.tips.2017.01.004","article-title":"Small Molecules That Sabotage Bacterial Virulence","volume":"38","author":"Johnson","year":"2017","journal-title":"Trends Pharmacol. 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