title: Cytotoxic/antiproliferative effects of new [1,2,4]triazolo[4,3-c] quinazolines in tumor cell lines HeLa and B16.
abstract: Quinazolines - 1,3-benzodiazines are biological active compounds, and some of them act as anticancer drugs. We evaluated cytotoxic/antiproliferative activity of new synthetically prepared [1,2,4]triazolo[4,3-c]quinazolines using tumor cell lines HeLa and B16. The in vitro cytotoxic studies of the most active derivative 3-(5-nitro-2-thienyl)-9-chloro-5-morpholin- 4-yl[1,2,4]triazolo[4,3-c]quinazoline (NTCHMTQ) were complemented by cell cycle analysis, and determination of apoptotic DNA fragmentation. Possible direct interaction of NTCHMTQ with calf thymus DNA was tested by the DNA-modified screen-printed electrode. Five quinazoline derivatives tested acted cytotoxically on both tumor cell lines. The melanoma cells B16 were more sensitive to quinazolines treatment than HeLa cells. The most effective derivative was NTCHMTQ which manifested significant in vitro cytotoxic/antiproliferative effect. NTCHMTQ at micromolar concentrations induced morphological changes and necrosis of B16 cells. NTCHMTQ at concentrations tested did not cause changes in cell cycle, did not induce apoptotic cell death in the B16 cells and did not even behave as a typical intercalating agent.
authors.affiliation: Institute of Biochemistry Nutrition and Health Protection, Faculty of Chemical and Food Technology, Slovak University of Technology, SK-81237 Bratislava, Slovak Republic. sona.jantova@stuba.sk
authors.forename: S
authors.initials: S
authors.lastname: Jantová
authors.forename: S
authors.initials: S
authors.lastname: Letasiová
authors.forename: R
authors.initials: R
authors.lastname: Ovádeková
authors.forename: M
authors.initials: M
authors.lastname: Múcková
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D016923:Cell Death / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D004249:DNA Damage; D004354:Drug Screening Assays, Antitumor; D006367:HeLa Cells; D006801:Humans; D020128:Inhibitory Concentration 50; D008546:Melanoma, Experimental / Q000188:drug therapy* / Q000473:pathology; D051379:Mice; D011799:Quinazolines / Q000494:pharmacology*; D014230:Triazoles / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D011799:Quinazolines; D014230:Triazoles