ABSTRACT
New copper(II) complexes of 2-alkylthio-5-arylmethylene-4H-imidazolin-4-ones: (5Z)-2-(methylsulfanyl)-3-(prop-2-en-1-yl)-5-(pyridin-2-ylmethylidene)-3,5-dihydro-4H-imidazol-4-one) (1a), (5Z,5'Z)-2,2'-(ethan-1,2-diyldisulfanyldiyl)bis(5-(2-pyridilmethylen)-3-allyl-3,5-dihydo-4Ð-imidazole-4-one) (2a) and (5Z,5'Z)-3,3'-hexan-1,6-diylbis[5-(2-pyridilmethylen)-2-methylthiotetrahydro-4Ð-imidazole-4-one)] (3a) were synthesized as possible anticancer drugs. Their structures were characterized by 1H NMR spectroscopy, elemental analysis, and X-ray crystallography. The composition of the complexes were found for 1a (Cu:L=1:1), 2a (Cu:L=2:1), and 3a (Cu:L=2:1). The chelation constants were found by competitive complexation with ethylenediamine tetraacetate: 1a (6.7±0.6)×1015M-1, 2a=(4.9±0.4)×1019M-2, and 3a (5.7±0.5)×1019M-2. Supramolecular binding with calf thymus DNA by competitive ethidium bromide quenching was made for complex 2a as the most promising anticancer model, the Stern-Volmer constants were found to be KSV=(8.0±0.4)×106M-1, Kq=(6.5±0.4)×105M-1. The binding of the complex 2a to BSA was made by the Scatchard method, the value of the constant is Kb=(1.9±0.2)×106M-1.
Subject(s)
Coordination Complexes/chemistry , Coordination Complexes/chemical synthesis , Copper/chemistry , DNA/chemistry , Serum Albumin, Bovine/chemistry , Thiohydantoins/chemistry , Animals , CattleABSTRACT
We have synthesized and characterized a panel of new binuclear mixed valence Cu(I,II) complexes containing substituted 2-alkylthio-5-arylmethylene-4H-imidazolin-4-ones with unusual structure. These complexes are shown to be cytotoxic for various cell lines. We have found that these compounds did not intercalate DNA, inhibited number of polymerases (telomerase predominantly), accumulated in the cell nucleus, and caused DNA degradation. Preliminary studies revealed that lead compound inhibited human breast adenocarcinoma growth in mice model.