{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T17:45:29Z","timestamp":1785433529452,"version":"3.56.0"},"reference-count":104,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2026,6,19]],"date-time":"2026-06-19T00:00:00Z","timestamp":1781827200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Medical University of Silesia","award":["BNW-1-022\/K\/6\/F"],"award-info":[{"award-number":["BNW-1-022\/K\/6\/F"]}]},{"award":["BNW-1-022\/K\/6\/F"],"award-info":[{"award-number":["BNW-1-022\/K\/6\/F"]}],"id":[{"id":"https:\/\/ror.org\/005k7hp45","id-type":"ROR","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007835","name":"Silesian University of Technology","doi-asserted-by":"publisher","award":["02\/040\/BK_26\/1080"],"award-info":[{"award-number":["02\/040\/BK_26\/1080"]}],"id":[{"id":"10.13039\/501100007835","id-type":"DOI","asserted-by":"publisher"}]},{"award":["02\/040\/BK_26\/1080"],"award-info":[{"award-number":["02\/040\/BK_26\/1080"]}],"id":[{"id":"https:\/\/ror.org\/02dyjk442","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Colorectal cancer is the third most commonly diagnosed cancer worldwide and the second leading cause of cancer-related deaths, while its resistance to treatment continues to represent a major therapeutic challenge. In the present study, a series of phenothiazine derivatives, including hybrids containing a 1,2,3-triazole linker and the zidovudine (AZT) fragment, were synthesized and evaluated for their anticancer activity against colorectal cancer cell lines HCT116 and HT-29 as well as non-cancerous BEAS-2B cells. Cytotoxic activity was determined using the Alamar Blue assay, while the mechanisms of action were investigated by flow cytometric analysis of apoptosis, cell cycle progression, and reactive oxygen species (ROS) generation. Additionally, changes in the expression of genes associated with apoptosis, oxidative stress, and DNA damage response were analyzed by RT-qPCR. The obtained results demonstrated that AZT-containing derivatives exhibited stronger anticancer activity than non-conjugated phenothiazine analogs. Compounds A9\u2013A12 induced pronounced apoptosis and significant disturbances in cell cycle progression, particularly in HCT116 cells. Among the analyzed derivatives, compound A9 displayed the most favorable overall biological profile, combining strong proapoptotic and cytotoxic activity with relatively high selectivity toward cancer cells and moderate effects on non-cancerous cells. The results indicate that molecular hybridization of phenothiazine derivatives with the AZT scaffold represents a promising strategy for the development of novel anticancer agents targeting colorectal cancer.<\/jats:p>","DOI":"10.3390\/ijms27125562","type":"journal-article","created":{"date-parts":[[2026,6,19]],"date-time":"2026-06-19T14:37:42Z","timestamp":1781879862000},"page":"5562","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Quinobenzothiazine\u2013AZT Hybrids Linked via 1,2,3-Triazole: Rational Design, Synthesis, and Biological Evaluation as Anticancer Agents"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-9665-1065","authenticated-orcid":false,"given":"Klaudia","family":"Giercuszkiewicz-Ha\u015bnik","sequence":"first","affiliation":[{"name":"Department of Systems Biology and Engineering, Silesian University of Technology, Akademicka Street 16, 44-100 Gliwice, Poland"},{"name":"Centre of Biotechnology, Silesian University of Technology, Krzywoustego Street 8, 44-100 Gliwice, Poland"},{"name":"Faculty of Medical Sciences in Katowice, Medical University of Silesia, 40-752 Katowice, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6263-9585","authenticated-orcid":false,"given":"Magdalena","family":"Skonieczna","sequence":"additional","affiliation":[{"name":"Department of Systems Biology and Engineering, Silesian University of Technology, Akademicka Street 16, 44-100 Gliwice, Poland"},{"name":"Centre of Biotechnology, Silesian University of Technology, Krzywoustego Street 8, 44-100 Gliwice, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5389-1079","authenticated-orcid":false,"given":"Beata","family":"Morak-M\u0142odawska","sequence":"additional","affiliation":[{"name":"Department of Organic Chemistry, Faculty of Pharmaceutical Sciences in Sosnowiec, Medical University of Silesia in Katowice, Jagiello\u0144ska Street 4, 41-200 Sosnowiec, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4144-990X","authenticated-orcid":false,"given":"Ma\u0142gorzata","family":"Jele\u0144","sequence":"additional","affiliation":[{"name":"Department of Organic Chemistry, Faculty of Pharmaceutical Sciences in Sosnowiec, Medical University of Silesia in Katowice, Jagiello\u0144ska Street 4, 41-200 Sosnowiec, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,6,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e70196","DOI":"10.1002\/cbf.70196","article-title":"Comprehensive Overview of Therapeutic Strategies in Colon Cancer: Chemotherapy, Targeted Therapy, and Immunotherapy","volume":"44","author":"Sulaiman","year":"2026","journal-title":"Cell Biochem. 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