{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T14:05:18Z","timestamp":1791641118632,"version":"4.3.4"},"reference-count":76,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2021,8,16]],"date-time":"2021-08-16T00:00:00Z","timestamp":1629072000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["410899006"],"award-info":[{"award-number":["410899006"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Hypoxia-regulated protein carbonic anhydrase IX (CA IX) is up-regulated in different tumor entities and correlated with poor prognosis in breast cancer patients. Due to the radio- and chemotherapy resistance of solid hypoxic tumors, derivatives of betulinic acid (BA), a natural compound with anticancer properties, seem to be promising to benefit these cancer patients. We synthesized new betulin sulfonamides and determined their cytotoxicity in different breast cancer cell lines. Additionally, we investigated their effects on clonogenic survival, cell death, extracellular pH, HIF-1\u03b1, CA IX and CA XII protein levels and radiosensitivity. Our study revealed that cytotoxicity increased after treatment with the betulin sulfonamides compared to BA or their precursors, especially in triple-negative breast cancer (TNBC) cells. CA IX activity as well as CA IX and CA XII protein levels were reduced by the betulin sulfonamides. We observed elevated inhibitory efficiency against protumorigenic processes such as proliferation and clonogenic survival and the promotion of cell death and radiosensitivity compared to the precursor derivatives. In particular, TNBC cells showed benefit from the addition of sulfonamides onto BA and revealed that betulin sulfonamides are promising compounds to treat more aggressive breast cancers, or are at the same level against less aggressive breast cancer cells.<\/jats:p>","DOI":"10.3390\/ijms22168808","type":"journal-article","created":{"date-parts":[[2021,8,16]],"date-time":"2021-08-16T21:27:45Z","timestamp":1629149265000},"page":"8808","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":30,"title":["Betulin Sulfonamides as Carbonic Anhydrase Inhibitors and Anticancer Agents in Breast Cancer Cells"],"prefix":"10.3390","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3214-8694","authenticated-orcid":false,"given":"Antje","family":"G\u00fcttler","sequence":"first","affiliation":[{"name":"Department of Radiotherapy, Martin-Luther-University of Halle-Wittenberg, Ernst-Grube-Str. 40, D-06120 Halle\/Saale, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yvonne","family":"Eiselt","sequence":"additional","affiliation":[{"name":"Department of Radiotherapy, Martin-Luther-University of Halle-Wittenberg, Ernst-Grube-Str. 40, D-06120 Halle\/Saale, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne","family":"Funtan","sequence":"additional","affiliation":[{"name":"Biozentrum, Martin-Luther-University of Halle-Wittenberg, Weinbergweg 22, D-06120 Halle\/Saale, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreas","family":"Thiel","sequence":"additional","affiliation":[{"name":"Institute of Biochemistry and Biotechnology, Martin-Luther University Halle-Wittenberg, Kurt-Mothes-Str. 3, D-06120 Halle\/Saale, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marina","family":"Petrenko","sequence":"additional","affiliation":[{"name":"Department of Radiotherapy, Martin-Luther-University of Halle-Wittenberg, Ernst-Grube-Str. 40, D-06120 Halle\/Saale, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacqueline","family":"Ke\u00dfler","sequence":"additional","affiliation":[{"name":"Department of Radiotherapy, Martin-Luther-University of Halle-Wittenberg, Ernst-Grube-Str. 40, D-06120 Halle\/Saale, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Iris","family":"Thondorf","sequence":"additional","affiliation":[{"name":"Institute of Biochemistry and Biotechnology, Martin-Luther University Halle-Wittenberg, Kurt-Mothes-Str. 3, D-06120 Halle\/Saale, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reinhard","family":"Paschke","sequence":"additional","affiliation":[{"name":"Biozentrum, Martin-Luther-University of Halle-Wittenberg, Weinbergweg 22, D-06120 Halle\/Saale, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dirk","family":"Vordermark","sequence":"additional","affiliation":[{"name":"Department of Radiotherapy, Martin-Luther-University of Halle-Wittenberg, Ernst-Grube-Str. 40, D-06120 Halle\/Saale, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthias","family":"Bache","sequence":"additional","affiliation":[{"name":"Department of Radiotherapy, Martin-Luther-University of Halle-Wittenberg, Ernst-Grube-Str. 40, D-06120 Halle\/Saale, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,8,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"394","DOI":"10.3322\/caac.21492","article-title":"Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries","volume":"68","author":"Bray","year":"2018","journal-title":"CA Cancer J. 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