{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T19:41:56Z","timestamp":1792611716399,"version":"4.5.0"},"reference-count":56,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2025,1,10]],"date-time":"2025-01-10T00:00:00Z","timestamp":1736467200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The biological and thermal properties of a class of synthetic dihydroimidazotriazinones were disclosed in this article for the first time. Molecules 1\u20136\u2014as potential innovative antimetabolites mimicking bicyclic aza-analogues of isocytosine\u2014were evaluated for their in vitro anticancer activity. Moreover, in vivo, in vitro, and ex vivo toxicity profiles of all the compounds were established in zebrafish, non-tumour cell, and erythrocyte models, respectively. Their antihaemolytic activity was also evaluated. Additionally, the thermal decomposition mechanism, path, and key thermal properties of heterocycles 1\u20136 were analysed. It was found that all the studied compounds revealed significant antiproliferative activities against tumour cells of the lung, cervix, ovary, and breast, as well as acute promyelocytic leukaemia cells, superior or comparable to that of an anticancer agent gemcitabine. Most of them were less toxic to non-tumour cells than this standard drug, and none had a haemolytic effect on red blood cells. All the tested heterocycles proved to be safer for zebrafish than a standard drug pemetrexed. Some exhibited the ability to inhibit oxidative haemolysis, suggesting their protective action on erythrocytes. The differential scanning calorimetry (DSC) analyses confirmed that all molecules melted within one narrow temperature range, proving their purity. The melting points depended solely on the type of substituent and increased as follows: 4 (R = 3-ClPh) &lt; 2 (R = 4-CH3Ph) = 3 (R = 4-OCH3Ph) &lt; 5 (R = 4-ClPh) = 1 (R = Ph) &lt; 6 (R = 3,4-Cl2Ph). The thermogravimetry\/differential thermogravimetry (TG\/DTG) studies confirmed high thermal stability of all the investigated heterocycles in inert (&gt;230 \u00b0C) and oxidising (&gt;260 \u00b0C) atmospheres, which depended directly on the R. The pyrolysis process included one main decomposition stage and was connected with the emission of NH3, HCN, CH3CN, HNCO, alkane, alkene, aromatic fragments, CO2 (for all the compounds), and HCl (for the molecule with 3,4-Cl2Ph), which was confirmed by FTIR and QMS analyses. In turn, the oxidative decomposition process of the tested polyazaheterocycles took place in two main stages connected with the formation of the same volatiles as those observed in an inert atmosphere and additionally with the release of N2, NO, CO, and H2O. These results proved that the pyrolysis and oxidative decomposition run through the radical mechanism connected with the additional reactions between radicals and oxygen in synthetic air. The favourable biological and thermal properties of this class of dihydroimidazotriazinones imply their usefulness as potential pharmaceutics.<\/jats:p>","DOI":"10.3390\/ijms26020541","type":"journal-article","created":{"date-parts":[[2025,1,10]],"date-time":"2025-01-10T03:48:11Z","timestamp":1736480891000},"page":"541","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["In Vitro, In Vivo, Ex Vivo Characterisation of Dihydroimidazotriazinones and Their Thermal Decomposition Course Studied by Coupled and Simultaneous Thermal Analysis Methods"],"prefix":"10.3390","volume":"26","author":[{"given":"Marta","family":"Worzakowska","sequence":"first","affiliation":[{"name":"Department of Polymer Chemistry, Institute of Chemical Sciences, Faculty of Chemistry, Maria Curie-Sk\u0142odowska University in Lublin, 33 Gliniana Street, 20-614 Lublin, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1576-097X","authenticated-orcid":false,"given":"Ma\u0142gorzata","family":"Sztanke","sequence":"additional","affiliation":[{"name":"Department of Medical Chemistry, Medical University of Lublin, 4A Chod\u017aki Street, 20-093 Lublin, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7628-313X","authenticated-orcid":false,"given":"Jolanta","family":"Rzymowska","sequence":"additional","affiliation":[{"name":"Department of Biology and Genetics, Medical University of Lublin, 4A Chod\u017aki Street, 20-093 Lublin, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1898-5245","authenticated-orcid":false,"given":"Krzysztof","family":"Sztanke","sequence":"additional","affiliation":[{"name":"Laboratory of Bioorganic Compounds Synthesis and Analysis, Medical University of Lublin, 4A Chod\u017aki Street, 20-093 Lublin, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,1,10]]},"reference":[{"key":"ref_1","first-page":"235","article-title":"Synthesis of new derivatives of 3-methyl-8-aryl-7,8-dihydro-6H-imidazo[2,1-c][1,2,4]triazin-4-one","volume":"59","author":"Sztanke","year":"2002","journal-title":"Acta Pol. 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