{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,16]],"date-time":"2026-02-16T11:06:44Z","timestamp":1771240004629,"version":"3.50.1"},"reference-count":29,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2026,2,11]],"date-time":"2026-02-11T00:00:00Z","timestamp":1770768000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100006769","name":"Russian Science Foundation","doi-asserted-by":"publisher","award":["22-63-00016"],"award-info":[{"award-number":["22-63-00016"]}],"id":[{"id":"10.13039\/501100006769","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Platinum(II)-based drugs, such as cisplatin, are commonly used to treat various types of cancer. However, their clinical use is limited due to a number of side effects and the development of resistance. To overcome these limitations, researchers have explored the development of platinum(IV) complexes as potential prodrugs that can be selectively activated under physiological conditions. In this study, we have incorporated synthetic analogs of vitamin E into the structure of platinum(IV) complexes to further improve their safety profile. The antioxidant properties of the compounds were evaluated using DPPH and CUPRAC assays, as well as lipid peroxidation inhibition models, revealing that incorporation of phenolic ligands confers pronounced antioxidant activity. Cytotoxicity was assessed towards cancer cell lines using the MTT assay, where the novel complexes showed significantly increased cytotoxic activity compared to cisplatin, while also demonstrating less toxicity toward normal fibroblast cells under the same in vitro conditions. These results suggest that the conjugation of antioxidant ligands to platinum(IV) scaffolds can modulate both redox processes and the biological activity of the resulting complexes. This proposed design strategy has the potential to create more effective platinum-based cancer treatments with enhanced biological characteristics.<\/jats:p>","DOI":"10.3390\/ijms27041750","type":"journal-article","created":{"date-parts":[[2026,2,11]],"date-time":"2026-02-11T17:45:36Z","timestamp":1770831936000},"page":"1750","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Novel Cytotoxic Pt(IV) Compounds with Improved Safety Profiles"],"prefix":"10.3390","volume":"27","author":[{"given":"Anastasia A.","family":"Antonets","sequence":"first","affiliation":[{"name":"Department of Chemistry, M.V. Lomonosov Moscow State University, Leninskie Gory 1\/3, Moscow 119991, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ksenia M.","family":"Voroshilkina","sequence":"additional","affiliation":[{"name":"Department of Chemistry, M.V. Lomonosov Moscow State University, Leninskie Gory 1\/3, Moscow 119991, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0069-8747","authenticated-orcid":false,"given":"Ilya A.","family":"Shutkov","sequence":"additional","affiliation":[{"name":"Department of Chemistry, M.V. Lomonosov Moscow State University, Leninskie Gory 1\/3, Moscow 119991, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9780-1490","authenticated-orcid":false,"given":"Dmitrii M.","family":"Mazur","sequence":"additional","affiliation":[{"name":"Department of Chemistry, M.V. Lomonosov Moscow State University, Leninskie Gory 1\/3, Moscow 119991, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tatiana P.","family":"Serkova","sequence":"additional","affiliation":[{"name":"Institute of Physiologically Active Compounds, Federal Research Center of Problems of Chemical Physics and Medicinal Chemistry, Russian Academy of Sciences, Chernogolovka 142432, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2887-1185","authenticated-orcid":false,"given":"Elena F.","family":"Shevtsova","sequence":"additional","affiliation":[{"name":"Department of Chemistry, M.V. Lomonosov Moscow State University, Leninskie Gory 1\/3, Moscow 119991, Russia"},{"name":"Institute of Physiologically Active Compounds, Federal Research Center of Problems of Chemical Physics and Medicinal Chemistry, Russian Academy of Sciences, Chernogolovka 142432, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8980-6016","authenticated-orcid":false,"given":"Dmitrii S.","family":"Yakovlev","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Bioinformatics, Volgograd State Medical University, Pavshich Bortsov Sq. 1, Volgograd 400131, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2043-8283","authenticated-orcid":false,"given":"Mariya S.","family":"Pshenichnikova","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Bioinformatics, Volgograd State Medical University, Pavshich Bortsov Sq. 1, Volgograd 400131, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Umida M.","family":"Ibragimova","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Bioinformatics, Volgograd State Medical University, Pavshich Bortsov Sq. 1, Volgograd 400131, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0162-0653","authenticated-orcid":false,"given":"Roman A.","family":"Litvinov","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Bioinformatics, Volgograd State Medical University, Pavshich Bortsov Sq. 1, Volgograd 400131, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7185-4826","authenticated-orcid":false,"given":"Alexander A.","family":"Spasov","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Bioinformatics, Volgograd State Medical University, Pavshich Bortsov Sq. 1, Volgograd 400131, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elena R.","family":"Milaeva","sequence":"additional","affiliation":[{"name":"Department of Chemistry, M.V. Lomonosov Moscow State University, Leninskie Gory 1\/3, Moscow 119991, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5821-1658","authenticated-orcid":false,"given":"Alexey A.","family":"Nazarov","sequence":"additional","affiliation":[{"name":"Department of Chemistry, M.V. Lomonosov Moscow State University, Leninskie Gory 1\/3, Moscow 119991, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,2,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"102925","DOI":"10.1016\/j.bioorg.2019.102925","article-title":"Cisplatin: The first metal based anticancer drug","volume":"88","author":"Ghosh","year":"2019","journal-title":"Bioorg. 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