Tumor selective Ru(III) Schiff bases complexes with strong in vitro activity toward cisplatin-resistant MDA-MB-231 breast cancer cells.

Novel ruthenium(III) complexes of general formula Na[RuCl2(L1-3-N,O)2] where L(1-3) denote deprotonated Schiff bases (HL1-HL3) derived from 5-substituted salicyladehyde and alkylamine (propyl- or butylamine) were prepared and characterized based on elemental analysis, mass spectra, infrared, electron spin/paramagnetic resonance (ESR/EPR) spectroscopy, and cyclovoltammetric study. Optimization of five isomers of complex C1 was done by DFT calculation. The interaction of C1-C3 complexes with DNA (Deoxyribonucleic acid) and BSA (Bovine serum albumin) was investigated by electron spectroscopy and fluorescence quenching. The cytotoxic activity of C1-C3 was investigated in a panel of four human cancer cell lines (K562, A549, EA.hy926, MDA-MB-231) and one human non-tumor cell line (MRC-5). Complexes displayed an apparent cytoselective profile, with IC50 values in the low micromolar range from 1.6 ± 0.3 to 23.0 ± 0.1 µM. Cisplatin-resistant triple-negative breast cancer cells MDA-MB-231 displayed the highest sensitivity to complexes, with Ru(III) compound containing two chlorides and two deprotonated N-propyl-5-chloro-salicylidenimine (hereinafter C1) as the most potent (IC50 = 1.6 µM), and approximately ten times more active than cisplatin (IC50 = 21.9 µM). MDA-MB-231 cells treated for 24 h with C1 presented with apoptotic morphology, as seen by acridine orange/ethidium bromide staining, while 48 h of treatment induced DNA fragmentation, and necrotic changes in cells, as seen by flow cytometry analysis. Drug-accumulation study by inductively coupled plasma mass spectrometry (ICP-MS) demonstrated markedly higher intracellular accumulation of C1 compared with cisplatin.

Vanadium(IV) complexes of salicylaldehyde-based furoic acid hydrazones: Synthesis, BSA binding and in vivo antidiabetic potential.

Solution synthesis afforded five novel neutral heteroleptic octahedral paramagnetic mononuclear oxidovanadium(IV) complexes of general composition [VO(bpy)L], where L is a dianionic tridentate ONO-donor hydrazone ligand derived from 2-furoic acid hydrazide and salicylaldehyde and its 5-substituted derivatives. Characterization was carried out by elemental analysis, mass spectrometry, infrared, electron, NMR, and EPR spectroscopy, cyclic voltammetry and conductometry. The molecular and crystal structure of the complex with 5-chloro-salicylaldehyde 2-furoic acid hydrazone (2) was determined. The quantum chemical properties of the vanadium complexes were studied at B3LYP and M062X levels with the lanl2dz basis set using Gaussian. Additionally, Swiss-ADME analysis was performed and complex (4), featuring a 5-nitro substituent on the hydrazone ligand, was selected for further investigation. The effects of the in vivo application of the complex on selected biochemical parameters in healthy and diabetic Wistar rats were investigated. Strong antidiabetic effect associated with moderate hypoalbuminemia was observed. Furthermore, the interaction of complexes with BSA was studied by spectrofluorimetry. A significant conformational change of BSA in the presence of vanadium complexes was found. Synchronous fluorescence spectra revealed significant changes in the tyrosine microenvironment of BSA. The FRET analysis was also used and the non-radiative process of energy transfer is elucidated. Thermodynamic data suggest van der Waals forces and hydrogen bonding as predominant binding modes of complexes to BSA.

Solvent effects on the crystallization and structure of ternary copper(ii) coordination compounds with l-threonine and 1,10-phenanthroline.

Solution-based and solid-state reactions of copper(ii) compounds, 1,10-phenanthroline and l-threonine were investigated. Eight new ternary coordination compounds were obtained: [Cu(l-Thr)(H2O)(phen)]2SO4∙10H2O (1a∙10H 2 O), [Cu(l-Thr)(H2O) (phen)]2SO4∙4.3H2O (1a∙4.3H 2 O), {[Cu(µ-l-Thr)(phen)]2SO4∙3.5H2O} n (1b∙3.5H 2 O), [Cu(l-Thr)(H2O)(phen)][Cu(l-Thr)(CH3OH)(phen)]SO4∙2H2O∙CH3OH (1c∙2H 2 O∙CH 3 OH), [Cu(l-Thr)(H2O)(phen)][Cu(l-Thr)(CH3OH)(phen)]SO4∙4H2O (1c∙4H 2 O), [Cu(l-Thr)(CH3OH)(phen)]2SO4∙H2O (1d∙H 2 O), [Cu(l-Thr)(H2O)(phen)][Cu(l-Thr)(CH3OH)(phen)][Cu(SO4)(l-Thr)(phen)]HSO4∙H2O∙3CH3OH (1e·H 2 O·3CH 3 OH), [Cu(l-Thr)(H2O)(phen)][Cu(l-Thr)(phen)(py)]SO4 (1f) (phen = 1,10-phenanthroline, l-Thr = l-threoninate, py = pyridine). X-ray crystal structure analysis of the prepared ternary coordination compounds revealed extensive hydrogen bonding and π-interactions that link complex species, anions and solvent molecules into 3D architectures. The water/methanol solvent molecules are found in pockets and/or channels in seven solvates. ESR spectra of different types of compounds were also investigated. In all measured compounds the unpaired electron of the copper(II) ion is located in the dx2-y2 orbital which is in agreement with elongated square-pyramidal geometry. Compound 1a∙10H 2 O showed substantial cytotoxic activity toward human hepatocellular carcinoma (HepG2) and acute monocytic leukaemia (THP-1) cell lines.