ABSTRACT
In this study we have investigated, for the first time to our knowledge, the antineoplastic activity of a planar pentadentate ligand (H2L.2H2O = 2', 2'''-(2,6-pyridindiyldiethylidyne)dioxamohydrazide dihydrate) and some of its metal coordination complexes [Cu(L)(H2O)].H2O, [Cu(HL)(H2O)]Cl04, [Co(L)(H20)2] 6H20, [Co(H2L)(H2O)(MeOH)](ClO4)2 and [Fe(L)(H2O)2]ClO4-3H2O, as well as of inorganic salts CuCl2 2H20, CoCl2 6H2O and FeCl3.6H2O of corresponding metal ions. The antiproliferative activity of these compounds was examined in a human melanoma cell line FemX with exposure time of 48 hours by performing two cytotoxicity tests: 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and sulforhodamine B (SRB) assay. Among these substances, the ligand H2L.2H2O expressed the greatest antineoplastic activity IC50 = 45.40 microM, while the IC50 of others could not be determined by SRB assay in the examined range of concentrations due to their low activity. FeCl3.6H2O showed stimulatory activity. We have found remarkable discrepancies between the results obtained by MTT assay and SRB assay that influence IC50 value as well as other measures of cytotoxicity, which led to the conlusion of uncertainty of using the MTT assay in evaluation of antineoplastic activity of organometalic complexes and inorganic metal salts.
Subject(s)
Cobalt/chemistry , Copper/chemistry , Formazans , Hydrazines/chemistry , Hydrazines/toxicity , Iron/chemistry , Pyridines/chemistry , Pyridines/toxicity , Tetrazolium Salts , Cell Line, Tumor , Cell Survival/drug effects , Humans , Inhibitory Concentration 50 , Ligands , Molecular Structure , Tetrazolium Salts/pharmacology , Thiazoles/pharmacologyABSTRACT
Protolytic equilibria in homogeneous and heterogeneous systems of lorazepam and oxazepam, which are sparingly soluble ampholytes from the class of 1,4-benzodiazepines, were studied at 25 degrees C and ionic strength of 0.1 M. Acidity constants and equilibrium constants in a heterogeneous system were determined. On the basis of the analysis of the corresponding 13C- and 1H-NMR spectra, deprotonation site in the molecules of the investigated compounds was predicted. Finally, the correlation between chemical shifts in the 1H-NMR spectra and the acidity of the amide proton of 1,4-benzodiazepines was established.
