{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T12:46:15Z","timestamp":1788439575487,"version":"build-2803163510"},"reference-count":51,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2021,1,26]],"date-time":"2021-01-26T00:00:00Z","timestamp":1611619200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01HL071158"],"award-info":[{"award-number":["R01HL071158"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["chemistry-europe.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["ChemMedChem"],"published-print":{"date-parts":[[2021,4,8]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Mitochondrial respiratory complex II (CII), also known as succinate dehydrogenase, plays a critical role in mitochondrial metabolism. Known but low potency CII inhibitors are selectively cytotoxic to cancer cells including the benzothiadiazine\u2010based anti\u2010hypoglycemic diazoxide. Herein, we study the structure\u2010activity relationship of benzothiadiazine derivatives for CII inhibition and their effect on cancer cells for the first time. A 15\u2010fold increase in CII inhibition was achieved over diazoxide, albeit with micromolar IC\n                    <jats:sub>50<\/jats:sub>\n                    values. Cytotoxicity evaluation of the novel derivatives resulted in the identification of compounds with much greater antineoplastic effect than diazoxide, the most potent of which possesses an IC\n                    <jats:sub>50<\/jats:sub>\n                    of 2.93\u00b10.07\u2005\u03bcM in a cellular model of triple\u2010negative breast cancer, with high selectivity over nonmalignant cells and more than double the potency of the clinical agent 5\u2010fluorouracil. No correlation between cytotoxicity and CII inhibition was found, thus indicating an as\u2010yet\u2010undefined mechanism of action of this scaffold. The derivatives described herein represent valuable hit compounds for therapeutic discovery in triple\u2010negative breast cancer.\n                  <\/jats:p>","DOI":"10.1002\/cmdc.202000729","type":"journal-article","created":{"date-parts":[[2020,12,17]],"date-time":"2020-12-17T23:13:52Z","timestamp":1608246832000},"page":"1143-1162","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Discovery of Halogenated Benzothiadiazine Derivatives with Anticancer Activity**"],"prefix":"10.1002","volume":"16","author":[{"given":"Bader I.","family":"Huwaimel","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical Sciences College of Pharmacy University of Nebraska Medical Center  Omaha NE 68106 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Myla","family":"Bhakta","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, School of Pharmacy Texas Tech University Health Sciences Center  Amarillo TX 79106 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6836-0518","authenticated-orcid":false,"given":"Chaitanya A.","family":"Kulkarni","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology University of Rochester Medical Center  Rochester NY 14642 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander S.","family":"Milliken","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology University of Rochester Medical Center  Rochester NY 14642 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Feifei","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Oral Biology College of Dentistry University of Nebraska Medical Center  Lincoln NE 68583 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aimin","family":"Peng","sequence":"additional","affiliation":[{"name":"Department of Oral Biology College of Dentistry University of Nebraska Medical Center  Lincoln NE 68583 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8639-8413","authenticated-orcid":false,"given":"Paul S.","family":"Brookes","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology University of Rochester Medical Center  Rochester NY 14642 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4947-5782","authenticated-orcid":false,"given":"Paul C.","family":"Trippier","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences College of Pharmacy University of Nebraska Medical Center  Omaha NE 68106 USA"},{"name":"Fred &amp; Pamela Buffett Cancer Center University of Nebraska Medical Center  Omaha NE 68106 USA"},{"name":"UNMC Center for Drug Discovery University of Nebraska Medical Center  Omaha NE 68106 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,1,26]]},"reference":[{"key":"e_1_2_6_1_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2017.04.018"},{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/emm.2013.85"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.drudis.2011.12.017"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrd.2018.174"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/0925-4439(95)00028-3"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/cddis.2015.110"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(17)38802-6"},{"key":"e_1_2_6_8_1","first-page":"6093","volume":"45","author":"Nadakavukaren K. 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