Novel Zn(II) complexes with non-steroidal anti-inflammatory ligand, flufenamic acid: Characterization, topoisomerase I inhibition activity, DNA and HSA binding studies.

A series of new Zn(II) complexes with flufenamic acid (flu) has been synthesized, namely [Zn3(dmso)2(flu)6] (1), [Zn3(flu)6(py)2] (2), [Zn(flu)2(tmen)] (3), [ZnCl(flu)(neo)] (4), and [Zn(cyclam)(flu)2] (5), where py=pyridine, tmen=N,N,N',N'-Tetramethylethylene diamine, neo=2,9-Dimethyl-1,10-phenanthroline and cyclam=1,4,8,11-Tetraazacyclotetradecane. These complexes have been characterized by infrared spectroscopy, single-crystal X-ray structure analysis, elemental and thermal analysis. All complexes contain deprotonated flufenamic acid coordinated via carboxylato group to zinc atoms, but their structures differ in the carboxylato binding mode, the coordination number of the central atom, the shape of the coordination polyhedra and the resultant supramolecular structures. Furthermore, an interaction of complexes with calf-thymus DNA (CT DNA) and human serum albumin (HSA) has been investigated by spectroscopic techniques. Moreover, the complexes 1 and 2 inhibit the catalytic activity of topoisomerase I at 60µM.

Interaction of a copper(II)-Schiff base complexes with calf thymus DNA and their antimicrobial activity.

The interaction of a copper complexes containing Schiff bases with calf thymus (CT) DNA was investigated by spectroscopic methods. UV-vis, fluorescence and CD spectroscopies were conducted to assess their binding ability with CT DNA. The binding constants K have been estimated from 0.8 to 9.1×10(4) M(-1). The percentage of hypochromism is found to be over 70% (from spectral titrations). The results showed that the copper(II) complexes could bind to DNA with an intercalative mode. Synergic action of Cu(II) complexes with ascorbic acid against Candida albicans induced the generation of free radicals and increased (more than 60 times) antimicrobial effect of these complexes.

Comparison of inhibition of murine leukaemia cell growth by 9-isothiocyanatoacridine and its cytosine adduct: involvement of thiols.

Cytotoxicity of two fluorescent acridine derivatives - 9-isothiocyanatoacridine (AcITC) and N-(9-acridinylthiocarbamoyl) cytosine (AcTCC) - a novel acridine compound, were investigated. Both substances have cytotoxic activity against the L1210 cellular line, IC50 values were in the micromolar range. Despite the high reactivity of AcITC towards thiols, its effects on leukemia cells were similar to naturally occurring isothiocyanates. AcITC changed the intracellular level of glutathione (GSH), and induced apoptosis. Arrest of cell cycle (G2/M-phase) was also observed. AcITC primarily reacted with -SH groups on cellular surface, and the study of the interaction of the isotiocyanate with human erythrocyte ghosts confirmed that the plasma membrane was the first place where AcITC bound. AcTCC does not react with cellular thiols; images obtained with fluorescent microscopy confirmed interaction of AcTCC with chromatine. Although AcTCC induced cellular arrest in the G2/M phase, apoptosis was not confirmed.

DNA binding properties and evaluation of cytotoxic activity of 9,10-bis-N-substituted (aminomethyl)anthracenes.

The results of DNA binding properties for four selected N-substituted 9,10-bis(aminomethyl)anthracenes are presented. DNA binding affinities were studied using UV-vis and fluorescence spectrophotometric titrations, CD spectroscopy, denaturation transition temperature (Tm) measurements and AM1 quantum chemical calculations. The results obtained indicate that the anthracene products intercalate into the stacked base pairs of DNA with binding constants, K, in the range 1.3-10.9 x 10(5)M(-1) and the binding site size in DNA-base pairs, n, extending over the range 2.4-4.6. Tm values increased in the presence of the anthryl probes, thereby reflecting an increased stability of the calf-thymus (CT) DNA double helix and rendering agreement with the spectrometric titration results. The synthesized compounds were tested against L1210 and HeLa tumor cell lines wherein the HeLa cells appeared to be more sensitive than the L1210 cells. 9,10-Bis{[2-(piperazin-1-yl)ethyl]aminomethyl}anthracene exhibited the highest activity of the tested compounds. Our findings were compared with those of a control drug bisantrene.

Determination of the binding affinities of plasmid DNA using fluorescent intercalators possessing an acridine skeleton.

Novel acridine derivatives, wherein the steric factor has been varied systematically through substitution at the 9 position of the acridine ring, were evaluated as convenient fluorescent probes for nucleic acid detection. The binding affinities of N-(9-acridinylthiocarbamoyl)amino acids (ATA) with plasmid DNA (pUC 19) were investigated using UV-vis spectrophotometry, fluorometric titration and quantum chemical calculations (AM1). From spectrofluorometric analysis, the binding constants for the DNA-ATA complexes were determined. To elucidate its DNA intercalation, the most preferable tautomeric structure of ATA was established by means of AM1 calculations.