Synthesis and cytotoxicity studies of bifunctional hybrids of nitrogen mustards with potential enzymes inhibitors based on melamine framework

J Enzyme Inhib Med Chem. 2012 Oct;27(5):619-27. doi: 10.3109/14756366.2011.604482. Epub 2011 Sep 8.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Proliferation / drug effects
  • Enzyme Inhibitors / chemistry*
  • Humans
  • Inhibitory Concentration 50
  • MCF-7 Cells
  • Magnetic Resonance Spectroscopy
  • Mechlorethamine / chemical synthesis*
  • Mechlorethamine / toxicity*
  • Triazines / chemistry*

Substances

  • Enzyme Inhibitors
  • Triazines
  • Mechlorethamine
  • melamine