{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,20]],"date-time":"2026-01-20T01:43:17Z","timestamp":1768873397867,"version":"3.49.0"},"reference-count":45,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2022,6,28]],"date-time":"2022-06-28T00:00:00Z","timestamp":1656374400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"European Union through the European Social Fund under the Operational Programme Knowledge Education Development 2014\u20132020","award":["POWR.03.02.00-00-I026\/17-00"],"award-info":[{"award-number":["POWR.03.02.00-00-I026\/17-00"]}]},{"name":"European Union through the European Social Fund under the Operational Programme Knowledge Education Development 2014\u20132020","award":["DEC--2\/2021\/IDUB\/V.6\/Si"],"award-info":[{"award-number":["DEC--2\/2021\/IDUB\/V.6\/Si"]}]},{"name":"Gda\u0144sk University of Technology","award":["POWR.03.02.00-00-I026\/17-00"],"award-info":[{"award-number":["POWR.03.02.00-00-I026\/17-00"]}]},{"name":"Gda\u0144sk University of Technology","award":["DEC--2\/2021\/IDUB\/V.6\/Si"],"award-info":[{"award-number":["DEC--2\/2021\/IDUB\/V.6\/Si"]}]},{"name":"SILICIUM SUPPORTING CORE R&amp;D FACILITIES\u2014\u2018Excellence Initiative\u2014Research University\u2019 program","award":["POWR.03.02.00-00-I026\/17-00"],"award-info":[{"award-number":["POWR.03.02.00-00-I026\/17-00"]}]},{"name":"SILICIUM SUPPORTING CORE R&amp;D FACILITIES\u2014\u2018Excellence Initiative\u2014Research University\u2019 program","award":["DEC--2\/2021\/IDUB\/V.6\/Si"],"award-info":[{"award-number":["DEC--2\/2021\/IDUB\/V.6\/Si"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>In the search for new compounds with antitumor activity, new potential anticancer agents were designed as molecular hybrids containing the structures of a triazine ring and a sulfonamide fragment. Applying the synthesis in solution, a base of new sulfonamide derivatives 20\u2013162 was obtained by the reaction of the corresponding esters 11\u201319 with appropriate biguanide hydrochlorides. The structures of the compounds were confirmed by spectroscopy (IR, NMR), mass spectrometry (HRMS or MALDI-TOF\/TOF), elemental analysis (C,H,N) and X-ray crystallography. The cytotoxic activity of the obtained compounds toward three tumor cell lines, HCT-116, MCF-7 and HeLa, was examined. The results showed that some of the most active compounds belonged to the R1 = 4-trifluoromethylbenzyl and R1 = 3,5-bis(trifluoromethyl)benzyl series and exhibited IC50 values ranging from 3.6 \u00b5M to 11.0 \u00b5M. The SAR relationships were described, indicating the key role of the R2 = 4-phenylpiperazin-1-yl substituent for the cytotoxic activity against the HCT-116 and MCF-7 lines. The studies regarding the mechanism of action of the active compounds included the assessment of the inhibition of MDM2-p53 interactions, cell cycle analysis and apoptosis induction examination. The results indicated that the studied compounds did not inhibit MDM2-p53 interactions but induced G0\/G1 and G2\/M cell cycle arrest in a p53-independent manner. Furthermore, the active compounds induced apoptosis in cells harboring wild-type and mutant p53. The compound design was conducted step by step and assisted by QSAR models that correlated the activity of the compounds against the HCT-116 cell line with molecular descriptors.<\/jats:p>","DOI":"10.3390\/ijms23137178","type":"journal-article","created":{"date-parts":[[2022,6,28]],"date-time":"2022-06-28T23:59:22Z","timestamp":1656460762000},"page":"7178","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["New 2-[(4-Amino-6-N-substituted-1,3,5-triazin-2-yl)methylthio]-N-(imidazolidin-2-ylidene)-4-chloro-5-methylbenzenesulfonamide Derivatives, Design, Synthesis and Anticancer Evaluation"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3080-0602","authenticated-orcid":false,"given":"\u0141ukasz","family":"Tomorowicz","sequence":"first","affiliation":[{"name":"Department of Organic Chemistry, Faculty of Pharmacy, Medical University of Gda\u0144sk, Al. Gen. J. Hallera 107, 80-416 Gda\u0144sk, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2007-5168","authenticated-orcid":false,"given":"Beata","family":"\u017bo\u0142nowska","sequence":"additional","affiliation":[{"name":"Department of Organic Chemistry, Faculty of Pharmacy, Medical University of Gda\u0144sk, Al. Gen. J. Hallera 107, 80-416 Gda\u0144sk, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8347-9659","authenticated-orcid":false,"given":"Krzysztof","family":"Szafra\u0144ski","sequence":"additional","affiliation":[{"name":"Department of Organic Chemistry, Faculty of Pharmacy, Medical University of Gda\u0144sk, Al. Gen. J. Hallera 107, 80-416 Gda\u0144sk, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2453-8214","authenticated-orcid":false,"given":"Jaros\u0142aw","family":"Chojnacki","sequence":"additional","affiliation":[{"name":"Department of Inorganic Chemistry, Faculty of Chemistry, Gda\u0144sk University of Technology, G. Narutowicza 11\/12, 80-233 Gda\u0144sk, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7269-2403","authenticated-orcid":false,"given":"Ryszard","family":"Konopi\u0144ski","sequence":"additional","affiliation":[{"name":"Maria Sk\u0142odowska-Curie National Research Institute of Oncology, ul. Roentgena 5, 02-781 Warszawa, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ewa A.","family":"Grzybowska","sequence":"additional","affiliation":[{"name":"Maria Sk\u0142odowska-Curie National Research Institute of Oncology, ul. Roentgena 5, 02-781 Warszawa, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2794-5031","authenticated-orcid":false,"given":"Jaros\u0142aw","family":"S\u0142awi\u0144ski","sequence":"additional","affiliation":[{"name":"Department of Organic Chemistry, Faculty of Pharmacy, Medical University of Gda\u0144sk, Al. Gen. J. Hallera 107, 80-416 Gda\u0144sk, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8105-2555","authenticated-orcid":false,"given":"Anna","family":"Kawiak","sequence":"additional","affiliation":[{"name":"Department of Biotechnology, Intercollegiate Faculty of Biotechnology, University of Gda\u0144sk and Medical University of Gda\u0144sk, ul. Abrahama 58, 80-307 Gda\u0144sk, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,6,28]]},"reference":[{"key":"ref_1","unstructured":"World Health Organization (WHO) (2022, February 03). Fact Sheet: Cancer. Available online: https:\/\/www.who.int\/news-room\/fact-sheets\/detail\/cancer."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"3279","DOI":"10.3390\/cancers3033279","article-title":"Assessment of the evolution of cancer treatment therapies","volume":"3","author":"Arruebo","year":"2011","journal-title":"Cancers"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.drup.2018.11.001","article-title":"Modulating ROS to overcome multidrug resistance in cancer","volume":"41","author":"Cui","year":"2018","journal-title":"Drug Resist. 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