{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,3]],"date-time":"2025-07-03T09:08:28Z","timestamp":1751533708244,"version":"3.37.3"},"reference-count":22,"publisher":"Bentham Science Publishers Ltd.","issue":"6","funder":[{"DOI":"10.13039\/501100001843","name":"SERB, Department of Science and Technology, India","doi-asserted-by":"publisher","award":["EMR\/2016\/003973"],"award-info":[{"award-number":["EMR\/2016\/003973"]}],"id":[{"id":"10.13039\/501100001843","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["eurekaselect.com"],"crossmark-restriction":true},"short-container-title":["ACAMC"],"published-print":{"date-parts":[[2020,6,14]]},"abstract":"<jats:sec>\n<jats:title>Background:<\/jats:title>\n<jats:p>The authors investigated the NF-\u03baB inhibitory role of three Benzisothiazolone (BIT)\nderivatives (1, 2 and 3) in Hodgkin\u2019s Lymphoma cells (L428) which constitutively express activated NF-\u03baB. All\nthree compounds showed dose-dependent NF-\u03baB inhibition (78.3, 70.7 and 34.6%) in the luciferase reporter\ngene assay and were found cytotoxic at IC50 values of 3.3\u03bcg\/ml, 4.35\u03bcg\/ml and 13.8\u03bcg\/ml, respectively by the\nXTT assay. BIT 1and BIT 2 (but not BIT 3) suppressed both NF-\u03baB subunits p50 and p65 in cytoplasmic and\nnuclear extracts in a concentration-dependent manner. Furthermore, BIT 1 showed a moderate synergistic effect\nwith the standard chemotherapy drugs etoposide and doxorubicin, whereas BIT 2 and 3 showed a moderate\nadditive effect to antagonistic effect. Cisplatin exhibited an antagonist effect on all the compounds tested under\nvarious concentrations, except in the case of 1.56\u03bcg\/ml of BIT 3 with 0.156\u03bcg\/ml of cisplatin. The compounds\nalso inhibited the migration of adherent human lung adenocarcinoma cells (A549) in vitro. We conclude that\nespecially BIT 1 and BIT 2 have in vitro anti-inflammatory and anti-cancer activities, which can be further\ninvestigated for future potential therapeutic use.<\/jats:p>\n<\/jats:sec>\n<jats:sec>\n<jats:title>Methods:<\/jats:title>\n<jats:p>Inspired by the electrophilic sulfur in Nuphar alkaloids, monomeric and dimeric benzisothiazolones\nwere synthesized from dithiodibenzoic acid and their NF-\u03baB inhibitory role was explored. NF-\u03baB inhibition and\ncytotoxicity of the synthesized derivatives were studied using luciferase reporter gene assay and XTTassay.\nImmunocytochemistry studies were performed using L428 cells. Cell migration assay was conducted using the\nA549 cell line. L428 cells were used to conduct combination studies and the results were plotted using\nCompuSyn software.<\/jats:p>\n<\/jats:sec>\n<jats:sec>\n<jats:title>Results:<\/jats:title>\n<jats:p>Benzisothiazolone derivatives exhibited cytotoxicity in Hodgkin\u2019s Lymphoma cells through NF-\u03baB\ninhibition. Potent compounds showed suppression of both NF-\u03baB subunits p50 and p65 in a concentrationdependent\nmanner, both in cytoplasmic and nuclear extracts. Combination studies suggest that benzisothiazolone\nderivatives possess a synergistic effect with etoposide and doxorubicin. Furthermore, the compounds\nalso inhibited the migration of A549 cells.<\/jats:p>\n<\/jats:sec>\n<jats:sec>\n<jats:title>Conclusion:<\/jats:title>\n<jats:p>Benzisothiazolones bearing one or two electrophilic sulfur atoms as part of the heterocyclic\nframework exhibited cytotoxicity in Hodgkin\u2019s Lymphoma cells through NF-\u03baB inhibition. In addition, these\nderivatives also exhibited a synergistic effect with etoposide and doxorubicin along with the ability to inhibit the\nmigration of A549 cells. Our study suggests that BIT-based new chemical entities could lead to potential anticancer\nagents.<\/jats:p>\n<\/jats:sec>","DOI":"10.2174\/1871520620666200213103513","type":"journal-article","created":{"date-parts":[[2020,2,13]],"date-time":"2020-02-13T16:35:01Z","timestamp":1581611701000},"page":"715-723","update-policy":"https:\/\/doi.org\/10.2174\/bsp_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Benzisothiazolone Derivatives Exhibit Cytotoxicity in Hodgkin\u2019s Lymphoma Cells through NF-\u03baB Inhibition and are Synergistic with Doxorubicin and Etoposide"],"prefix":"10.2174","volume":"20","author":[{"given":"Natarajan","family":"Nandakumar","sequence":"first","affiliation":[{"name":"The Shraga Segal Department of Microbiology, Immunology and Genetics, Faculty of Health Sciences and Oncology Laboratory, Soroka University Medical Center, Ben-Gurion University of the Negev, Beer Sheva, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6577-2357","authenticated-orcid":true,"given":"Pushparathinam","family":"Gopinath","sequence":"additional","affiliation":[{"name":"Department of Chemistry, SRM Institute of Science and Technology, Chennai, Tamilnadu, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jacob","family":"Gopas","sequence":"additional","affiliation":[{"name":"The Shraga Segal Department of Microbiology, Immunology and Genetics, Faculty of Health Sciences and Oncology Laboratory, Soroka University Medical Center, Ben-Gurion University of the Negev, Beer Sheva, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kannoth M.","family":"Muraleedharan","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Indian Institute of Technology Madras, Chennai, Tamilnadu, India"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"965","reference":[{"key":"ref=1","doi-asserted-by":"publisher","first-page":"2700","DOI":"10.1182\/blood-2006-07-025809","volume":"109","author":"Jost P.J.","year":"2007","unstructured":"Jost P.J.; Ruland J.; Aberrant NF-kappaB signaling in lymphoma: mechanisms, consequences, and therapeutic implications. 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