{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T14:18:02Z","timestamp":1785421082828,"version":"3.56.0"},"reference-count":58,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2026,7,23]],"date-time":"2026-07-23T00:00:00Z","timestamp":1784764800000},"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":["Pharmaceuticals"],"abstract":"<jats:p>Background\/Objectives: Colorectal cancer is one of the most common malignancies worldwide and is frequently associated with dysregulation of apoptosis, oxidative stress, and the p53 regulatory axis. The development of novel compounds capable of modulating these pathways remains an important challenge in anticancer drug discovery. This study aimed to evaluate the biological activity of newly synthesized triazole\u2013diquinothiazine derivatives in colorectal cancer cells and to identify the most promising lead compound for further development. Methods: The synthesized derivatives were evaluated in HCT116 colorectal cancer cells harboring wild-type TP53 and in normal BEAS-2B cells. Cytotoxicity, apoptosis, cell cycle distribution, intracellular reactive oxygen species (ROS) generation, and the expression of genes associated with apoptosis, oxidative stress, and inflammatory response were analyzed. Results: The investigated compounds exhibited diverse biological effects, including modulation of apoptosis, cell cycle progression, and oxidative stress. Among the tested derivatives, compound B5 demonstrated the most favorable biological profile, characterized by a more pronounced biological response in HCT116 cells than in BEAS-2B cells, increased ROS generation, reduced MDM2 expression, and a marked induction of early apoptosis. Conclusions: The obtained results indicate that triazole\u2013diquinothiazine derivatives represent promising lead structures for further optimization. In particular, compound B5 warrants additional mechanistic and preclinical studies to evaluate its potential as a candidate for colorectal cancer therapy.<\/jats:p>","DOI":"10.3390\/ph19081133","type":"journal-article","created":{"date-parts":[[2026,7,23]],"date-time":"2026-07-23T09:11:26Z","timestamp":1784797886000},"page":"1133","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Novel Triazole\u2013Diquinothiazine Hybrids Modulating Apoptosis and Stress Pathways in Colorectal Cancer Cells"],"prefix":"10.3390","volume":"19","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":[[2026,7,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Ebenezer, O., Jordaan, M.A., Carena, G., Bono, T., Shapi, M., and Tuszynski, J.A. 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