{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,11]],"date-time":"2026-04-11T07:02:04Z","timestamp":1775890924945,"version":"3.50.1"},"reference-count":99,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2024,2,27]],"date-time":"2024-02-27T00:00:00Z","timestamp":1708992000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["chemistry-europe.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["ChemMedChem"],"published-print":{"date-parts":[[2024,5,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>This study examines efficiency of a newly synthesized sulfonamide derivative 2\u2010bromo\u2010<jats:italic>N<\/jats:italic>\u2010(4\u2010sulfamoylphenyl)propanamide (MMH\u20101) on the inhibition of Carbonic Anhydrase IX (CA IX), which is overexpressed in many solid tumors including breast cancer. The inhibitory potential of MMH\u20101 compound against its four major isoforms, including cytosolic isoforms <jats:italic>h<\/jats:italic>CA I and II, as well as tumor\u2010associated membrane\u2010bound isoforms <jats:italic>h<\/jats:italic>CA IX and XII, was evaluated. To this context, the cytotoxic effect of MMH\u20101 on cancer and normal cells was tested and found to selectively affect MDA\u2010MB\u2010231 cells. MMH\u20101 reduced cell proliferation by holding cells in the G0\/G1 phase (72\u2009%) and slowed the cells\u2032 wound healing capacity. MMH\u20101 inhibited CA IX under both hypoxic and normoxic conditions and altered the morphology of triple negative breast cancer cells. In MDA\u2010MB\u2010231 cells, inhibition of CA IX was accompanied by a decrease in extracellular pH acidity (7.2), disruption of mitochondrial membrane integrity (80\u2009%), an increase in reactive oxygen levels (25\u2009%), and the triggering of apoptosis (40\u2009%). In addition, the caspase cascade (CASP\u20103, \u20108, \u20109) was activated in MDA\u2010MB\u2010231 cells, triggering both the extrinsic and intrinsic apoptotic pathways. The expression of pro\u2010apoptotic regulatory proteins (Bad, Bax, Bid, Bim, Cyt\u2010c, Fas, FasL, TNF\u2010a, TNF\u2010R1, HTRA, SMAC, Casp\u20103, \u20108, P21, P27, and P53) was increased, while the expression of anti\u2010apoptotic proteins, apoptosis inhibitor proteins (IAPs), and heat shock proteins (HSPs) (Bcl\u20102, Bcl\u2010w, cIAP\u20102, HSP27, HSP60, HSP70, Survivin, Livin, and XIAP) was decreased. These results propose that the MMH\u20101 compound could triggers apoptosis in MDA\u2010MB\u2010231 cells via the pH\/MMP\/ROS pathway through the inhibition of CA IX. This compound is thought to have high potential and promising anticancer properties in the treatment of aggressive tumors.<\/jats:p>","DOI":"10.1002\/cmdc.202300680","type":"journal-article","created":{"date-parts":[[2024,2,7]],"date-time":"2024-02-07T05:38:31Z","timestamp":1707284311000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Effective Anticancer Potential of a New Sulfonamide as a Carbonic Anhydrase IX Inhibitor Against Aggressive Tumors"],"prefix":"10.1002","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9469-4757","authenticated-orcid":false,"given":"Ismail","family":"Koyuncu","sequence":"first","affiliation":[{"name":"Department of Medical Biochemistry Faculty of Medicine Harran University  Sanliurfa Turkey Tel."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8911-7763","authenticated-orcid":false,"given":"Ebru","family":"Temiz","sequence":"additional","affiliation":[{"name":"Program of Medical Promotion and Marketing Health Services Vocational School Harran University  Sanliurfa Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4351-1719","authenticated-orcid":false,"given":"Eray Metin","family":"G\u00fcler","sequence":"additional","affiliation":[{"name":"Department of Medical Biochemistry Faculty of Hamidiye Medicine University of Health Sciences  Istanbul Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3012-7582","authenticated-orcid":false,"given":"Mustafa","family":"Durgun","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Faculty of Arts and Sciences Harran University  Sanliurfa Turkey Tel."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2058-5440","authenticated-orcid":false,"given":"Ozg\u00fcr","family":"Yuksekdag","sequence":"additional","affiliation":[{"name":"Department of Medical Biochemistry Faculty of Medicine Harran University  Sanliurfa Turkey Tel."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0669-7481","authenticated-orcid":false,"given":"Simone","family":"Giovannuzzi","sequence":"additional","affiliation":[{"name":"Department of Neurofarba Section of Pharmaceutical and Nutriceutical Sciences Universit\u00e0 degli Studi di Firenze, Sesto Fiorentino  Florence Italy Tel."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4262-0323","authenticated-orcid":false,"given":"Claudiu T.","family":"Supuran","sequence":"additional","affiliation":[{"name":"Department of Neurofarba Section of Pharmaceutical and Nutriceutical Sciences Universit\u00e0 degli Studi di Firenze, Sesto Fiorentino  Florence Italy Tel."}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2024,2,27]]},"reference":[{"key":"e_1_2_9_1_1","doi-asserted-by":"publisher","DOI":"10.1177\/21501319221105248"},{"key":"e_1_2_9_2_1","doi-asserted-by":"crossref","unstructured":"K. Nurgali R.\u2005T. Jagoe R. Abalo Vol. 9 Frontiers Media SA 2018 p. 245.","DOI":"10.3389\/fphar.2018.00245"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2021.113837"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41416-019-0642-z"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12943-019-1089-9"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1042\/BCJ20160115"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.3390\/metabo7030048"},{"key":"e_1_2_9_8_1","doi-asserted-by":"crossref","unstructured":"C.\u2005T. Supuran Vol. 22 MDPI 2017 p. 1642.","DOI":"10.3390\/molecules22101642"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmcl.2015.01.026"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmcl.2012.10.003"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2013.03.012"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2011.08.015"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmc.2013.05.029"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2016.08.060"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmcl.2017.03.018"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1080\/14756366.2018.1481403"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms22116098"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijbiomac.2021.12.190"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.0c00830"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrd.2016.253"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2018.11.017"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1080\/14756366.2018.1532419"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bioorg.2016.12.007"},{"key":"e_1_2_9_24_1","first-page":"888","volume":"60","author":"Durgun M.","year":"2021","journal-title":"Ind. J. Chem.-Sec. B (IJC-B)"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molstruc.2016.02.062"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmcl.2015.04.007"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmc.2016.01.020"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmcl.2004.10.070"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1107\/S1600536812046806"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.33588"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcrpr.2017.07.001"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41392-020-00451-w"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21731"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers13030427"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.7150\/thno.57828"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.3109\/14756366.2012.672983"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers14143297"},{"key":"e_1_2_9_38_1","first-page":"69","volume":"6","author":"Kuijk S. J.","year":"2016","journal-title":"Front. Oncol."},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.1080\/14756366.2020.1772250"},{"key":"e_1_2_9_40_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrd2467"},{"key":"e_1_2_9_41_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-019-56847-4"},{"key":"e_1_2_9_42_1","doi-asserted-by":"publisher","DOI":"10.3390\/molecules27051604"},{"key":"e_1_2_9_43_1","doi-asserted-by":"publisher","DOI":"10.4155\/fmc.14.68"},{"key":"e_1_2_9_44_1","doi-asserted-by":"publisher","DOI":"10.1080\/17460441.2017.1253677"},{"key":"e_1_2_9_45_1","doi-asserted-by":"publisher","DOI":"10.1517\/13543776.16.1.27"},{"key":"e_1_2_9_46_1","doi-asserted-by":"publisher","DOI":"10.1517\/13543776.2013.790957"},{"key":"e_1_2_9_47_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bioorg.2017.11.010"},{"key":"e_1_2_9_48_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2013.12.042"},{"key":"e_1_2_9_49_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmc.2015.02.027"},{"key":"e_1_2_9_50_1","doi-asserted-by":"publisher","DOI":"10.1517\/13543776.2013.780598"},{"key":"e_1_2_9_51_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrd3554"},{"key":"e_1_2_9_52_1","doi-asserted-by":"publisher","DOI":"10.1517\/13543776.2013.798648"},{"key":"e_1_2_9_53_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms20236080"},{"key":"e_1_2_9_54_1","doi-asserted-by":"publisher","DOI":"10.3390\/molecules23051045"},{"key":"e_1_2_9_55_1","doi-asserted-by":"publisher","DOI":"10.1080\/14756366.2021.2004592"},{"key":"e_1_2_9_56_1","doi-asserted-by":"publisher","DOI":"10.1021\/jm101541x"},{"key":"e_1_2_9_57_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10863-018-9749-9"},{"key":"e_1_2_9_58_1","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.110.167270"},{"key":"e_1_2_9_59_1","doi-asserted-by":"publisher","DOI":"10.1080\/14756366.2022.2053526"},{"key":"e_1_2_9_60_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2019.02.044"},{"key":"e_1_2_9_61_1","doi-asserted-by":"publisher","DOI":"10.2147\/OTT.S249756"},{"key":"e_1_2_9_62_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms19020448"},{"key":"e_1_2_9_63_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13058-022-01532-0"},{"key":"e_1_2_9_64_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrc3579"},{"key":"e_1_2_9_65_1","doi-asserted-by":"publisher","DOI":"10.1080\/07357900802653464"},{"key":"e_1_2_9_66_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms21082983"},{"key":"e_1_2_9_67_1","doi-asserted-by":"publisher","DOI":"10.1111\/boc.201900099"},{"key":"e_1_2_9_68_1","doi-asserted-by":"publisher","DOI":"10.3390\/metabo8010013"},{"key":"e_1_2_9_69_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-10-4261"},{"key":"e_1_2_9_70_1","doi-asserted-by":"publisher","DOI":"10.1038\/onc.2017.219"},{"key":"e_1_2_9_71_1","first-page":"2585","volume":"41","author":"G\u00fcttler A.","year":"2019","journal-title":"Oncol. Rep."},{"key":"e_1_2_9_72_1","doi-asserted-by":"publisher","DOI":"10.1038\/labinvest.2016.103"},{"key":"e_1_2_9_73_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cbi.2018.02.014"},{"key":"e_1_2_9_74_1","first-page":"7075","volume":"60","author":"Wykoff C. C.","year":"2000","journal-title":"Cancer Res."},{"key":"e_1_2_9_75_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.febslet.2004.10.043"},{"key":"e_1_2_9_76_1","doi-asserted-by":"publisher","DOI":"10.5306\/wjco.v3.i7.98"},{"key":"e_1_2_9_77_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms22116098"},{"key":"e_1_2_9_78_1","doi-asserted-by":"publisher","DOI":"10.1080\/14756366.2018.1524380"},{"key":"e_1_2_9_79_1","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2020.01462"},{"key":"e_1_2_9_80_1","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.422"},{"key":"e_1_2_9_81_1","doi-asserted-by":"publisher","DOI":"10.1038\/onc.2010.455"},{"key":"e_1_2_9_82_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.cdd.4402047"},{"key":"e_1_2_9_83_1","first-page":"19","volume":"50","author":"Sadowski-Debbing K.","year":"2002","journal-title":"Arch. Immunol. Ther. Exp."},{"key":"e_1_2_9_84_1","doi-asserted-by":"publisher","DOI":"10.1080\/14756366.2019.1579805"},{"key":"e_1_2_9_85_1","doi-asserted-by":"publisher","DOI":"10.1080\/14756366.2021.1909580"},{"key":"e_1_2_9_86_1","doi-asserted-by":"publisher","DOI":"10.1158\/2159-8290.CD-19-0050"},{"key":"e_1_2_9_87_1","doi-asserted-by":"publisher","DOI":"10.1080\/01926230701320337"},{"key":"e_1_2_9_88_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pneurobio.2006.07.006"},{"key":"e_1_2_9_89_1","doi-asserted-by":"publisher","DOI":"10.1038\/onc.2013.63"},{"key":"e_1_2_9_90_1","first-page":"3779","volume":"15","author":"Dizdar L.","year":"2018","journal-title":"Oncology Letters"},{"key":"e_1_2_9_91_1","first-page":"3489","volume":"16","author":"Li Y.","year":"2018","journal-title":"Oncology Letters"},{"key":"e_1_2_9_92_1","first-page":"1","author":"Cremona M.","year":"2022","journal-title":"Br. J. Cancer"},{"key":"e_1_2_9_93_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pneurobio.2010.05.002"},{"key":"e_1_2_9_94_1","first-page":"1551","volume":"38","author":"Dimas D. T.","year":"2018","journal-title":"Anticancer Res."},{"key":"e_1_2_9_95_1","doi-asserted-by":"publisher","DOI":"10.1186\/1755-1536-5-7"},{"key":"e_1_2_9_96_1","volume":"2021","author":"Li N.","year":"2021","journal-title":"Oxidative Medicine and Cellular Longevity"},{"key":"e_1_2_9_97_1","doi-asserted-by":"publisher","DOI":"10.3389\/fncel.2015.00319"},{"key":"e_1_2_9_98_1","doi-asserted-by":"publisher","DOI":"10.1080\/1061186X.2021.1920025"},{"key":"e_1_2_9_99_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcp.2022.115096"}],"container-title":["ChemMedChem"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/chemistry-europe.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cmdc.202300680","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,12]],"date-time":"2025-10-12T12:29:08Z","timestamp":1760272148000},"score":1,"resource":{"primary":{"URL":"https:\/\/chemistry-europe.onlinelibrary.wiley.com\/doi\/10.1002\/cmdc.202300680"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,2,27]]},"references-count":99,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2024,5,2]]}},"alternative-id":["10.1002\/cmdc.202300680"],"URL":"https:\/\/doi.org\/10.1002\/cmdc.202300680","archive":["Portico"],"relation":{},"ISSN":["1860-7179","1860-7187"],"issn-type":[{"value":"1860-7179","type":"print"},{"value":"1860-7187","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,2,27]]},"assertion":[{"value":"2023-12-04","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-02-27","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e202300680"}}