title: Synthesis and cytotoxicity studies of bifunctional hybrids of nitrogen mustards with potential enzymes inhibitors based on melamine framework.
abstract: The new class of hybrid anticancer drugs were obtained by selective functionalization of the triazine scaffold. These were prepared by rearrangement of mono-, bis- and/or tris-(1,3,5-triazin-2-yl)-1,4-diazabicyclo[2.2.2]octanium chlorides leading to formation of 2-chloroethylamino fragments attached to 1,3,5-triazine via one, two or three piperazine rings respectively. Their inhibitory effect was found strongly dependent on the structure of substituents in triazine ring. The anti-proliferative activity of the hybrids evaluated in vitro by using mammalian tumour cells estimated as IC(50) was in the range 0.62-139,78 µM. Both cytotoxicity and alkylating activity depended on the substituents of triazine ring, however, also the mono-functional analogues of nitrogen mustards, which are unable to form liaisons between two DNA strands, induced apoptosis and necrosis in the tested cells.
authors: Institute of Organic Chemistry, Technical University of Lodz, Poland.
authors: Beata
authors: B
authors: Kolesinska
authors: Konrad
authors: K
authors: Barszcz
authors: Zbigniew J
authors: ZJ
authors: Kaminski
authors: Danuta
authors: D
authors: Drozdowska
authors: Joanna
authors: J
authors: Wietrzyk
authors: Marta
authors: M
authors: Switalska
mesh_terms: D049109:Cell Proliferation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000737:chemistry*; D006801:Humans; D020128:Inhibitory Concentration 50; D061986:MCF-7 Cells; D009682:Magnetic Resonance Spectroscopy; D008466:Mechlorethamine / Q000138:chemical synthesis* / Q000633:toxicity*; D014227:Triazines / Q000737:chemistry*
chemical_list: D004791:Enzyme Inhibitors; D014227:Triazines; D008466:Mechlorethamine; C011907:melamine