title: In vitro effects of a new fused azaisocytosine-like congener on relative cell proliferation, necrosis and cell cycle in cancer and normal cell cultures.
abstract: The study was aimed at describing the mode of action of an innovative drug-like congener of fused azaisocytosine-EIMTC (ethyl 8-(4-methoxyphenyl)-4-oxo-6,7-dihydroimidazo[2,1-c][1,2,4]triazine-3-carboxylate)-on cancer cells in early in vitro oncology-related bioassays. Micromolar concentrations of EIMTC were effective at inhibiting the growth of two types of malignant multiple myeloma cells (including cells resistant to thalidomide) while having less cytotoxic effect on normal HSF cells. Furthermore, EIMTC was disclosed as capable of producing the statistically significant decrease in the number of cells in the S phase (in HeLa, TOV112D, T47D and Vero cells) and in the G2/M phase (in TOV112D cells) as well as evoking the distinctly higher necrosis rates in malignant than normal cells of the same epithelial origin. These results are promising in the sense that the bicyclic nucleobase-like structure related to azaisocytosine may target epithelial cancer cells and inhibit their growth while having less effect on normal cells. This may be due to induction of necrosis.
authors.affiliation: Chair and Department of Medical Chemistry, Medical University, 4A Chodźki Street, 20-093, Lublin, Poland. malgorzata.sztanke@umlub.pl.
authors.forename: Małgorzata
authors.identifier: http://orcid.org/0000-0003-1576-097X
authors.initials: M
authors.lastname: Sztanke
authors.affiliation: Department of Biology and Genetics, Medical University, 4A Chodźki Street, 20-093, Lublin, Poland.
authors.forename: Jolanta
authors.initials: J
authors.lastname: Rzymowska
authors.affiliation: Laboratory of Bioorganic Synthesis and Analysis, Chair and Department of Medical Chemistry, Medical University, 4A Chodźki Street, 20-093, Lublin, Poland.
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Sztanke
mesh_terms: D002455:Cell Division / Q000187:drug effects*; D003596:Cytosine / Q000031:analogs & derivatives* / Q000494:pharmacology; D016195:G2 Phase / Q000187:drug effects*; D006367:HeLa Cells; D006801:Humans; D009101:Multiple Myeloma / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology
chemical_list: C093270:isocytosine; D003596:Cytosine
keywords: Anti-multiple myeloma activity; Cell cycle arrest; Cell death mode; Cytotoxicity; EIMTC-mediated necrosis