Cytotoxic activities of new iron(III) and nickel(II) chelates of some S-methyl-thiosemicarbazones on K562 and ECV304 cells

The S-methyl-thiosemicarbazones of the 2- hydroxy-R-benzaldehyde (R= H, 3-OH 3-OCH3 or 4-OCH3) reacted with the corresponding aldehydes in the presence of FeCl3 and NiCl2. New ONNO chelates of iron(III) and nickel (II) with hydroxy- or methoxy-substitued N1,N4-diarylidene-Smethyl- thiosemicarbazones were characterized by means of elemental analysis, conductivity and magnetic measurements, UV-Vis, IR and 1H-NMR spectroscopies. Cytotoxic activities of the compounds were determined using K562 chronic myeloid leukemia and ECV304 human endothelial cell lines by MTT assay. It was determined that monochloro N1-4- methoxysalicylidene-N4-4-methoxysalicylidene-S-methylthiosemicarbazidato- iron(III) complex showed selective anti-leukemic effects in K562 cells while has no effect in ECV304 cells in the 0.53 μg/ml (IC50) concentrations. Also, some methoxy-substitued nickel(II) chelates exhibit high cytotoxic activitiy against both of these cell lines in low concentrations. Cytotoxicity data were evaluated depending on cell lines origin and position of the substituents on aromatic rings

Nickel(II)-PPh3 complexes with ONS and ONN chelating thiosemicarbazones: synthesis and inhibition potential on influenza A viruses

Tetra-coordinated nickel(II) complexes of two ONS (1, 2) and seven ONN (3a-3g) chelating 2-hydroxy-3-methoxy-benzaldehyde thiosemicarbazones were synthesized. The dibasic ligands and complexes bearing PPh3 as a coligand were characterized by means of analytical and spectroscopic data. Cytotoxic activities of the ligands and nickel(II) complexes were determined using the MTT assay in vitro against MDCK cells, and then all the compounds were tested on influenza virus replication by plaque assays. The compounds showed GI(50) values varying from concentrations of 15.9 up to 161.8 mu g/mL for MDCK cells. The plaque assays indicated that one ONS (1) and two ONN (3c and 3d) chelate structures have considerable antiviral effects on influenza A viruses at lower concentrations than the GI(50) values for MDCK cells. The ligands and other complexes did not show any inhibitory effects on influenza virus plaque formation. The effects of the compounds on the influenza virus and structure-antiviral activity relationships were discussed based on the donor atoms and S-alkyl substituents

Nickel(II)-PPh<inf>3</inf> complexes with ONS and ONN chelating thiosemicarbazones: synthesis and inhibition potential on influenza A viruses

Tetra-coordinated nickel(II) complexes of two ONS (1, 2) and seven ONN (3a-3g) chelating 2-hydroxy-3-methoxy-benzaldehyde thiosemicarbazones were synthesized. The dibasic ligands and complexes bearing PPh3 as a coligand were characterized by means of analytical and spectroscopic data. Cytotoxic activities of the ligands and nickel(II) complexes were determined using the MTT assay in vitro against MDCK cells, and then all the compounds were tested on influenza virus replication by plaque assays. The compounds showed GI(50) values varying from concentrations of 15.9 up to 161.8 mu g/mL for MDCK cells. The plaque assays indicated that one ONS (1) and two ONN (3c and 3d) chelate structures have considerable antiviral effects on influenza A viruses at lower concentrations than the GI(50) values for MDCK cells. The ligands and other complexes did not show any inhibitory effects on influenza virus plaque formation. The effects of the compounds on the influenza virus and structure-antiviral activity relationships were discussed based on the donor atoms and S-alkyl substituents

Synthesis, molecular modelling, FT-IR, Raman and NMR characterization, molecular docking and ADMET study of new nickel(II) complex with an N4-tetradentate thiosemicarbazone

© 2020, © 2020 Informa UK Limited, trading as Taylor & Francis Group.A new nickel(II) complex was synthesized by using S-propyl-thiosemicarbazide and 2-amino-3,5-dibromobenzaldehyde. The complex, obtained by the template effect of nickel ions, was structurally analysed by experimental and theoretical vibrational spectroscopy, NMR and density functional theory (DFT) calculations. By using DFT/B3LYP method with 6-311++G(d, p) basis set, the most stable molecular structure of the title molecule was calculated. The fundamental vibrational wavenumbers, IR and Raman intensities for the optimized structure of the molecule under investigation were determined and compared with the experimental vibrational spectra. The vibrational assignment was achieved using the calculated potential energy distributions of the vibrational modes. Moreover, the molecular electrostatic potential (MEP), the highest occupied molecular orbital (HOMO) and the lowest occupied molecular orbital (LUMO) energies were calculated, Molecular docking of the molecule was carried out against DNA in order to identify the potential inhibitory action of the title compound. The findings suggested that the aforementioned compound has a strong binding affinity to interact with DNA residues DT8, DC9, DG12, DG16, DA17, and DA18 through the intermolecular hydrogen bonds. Also the performed in silico ADMET analysis was the prediction of the synthesized molecule’s pharmacokinetic and toxicity profile expressing good oral drug like actions and non-toxic nature. The complex has been shown to have the possibility to become a model molecule for drug development processes. Communicated by Ramaswamy H. Sarma

Iron(III) and nickel(ii) complexes as potential anticancer agents: Synthesis, physicochemical and structural properties, cytotoxic activity and DNA interactions

Template reactions of 2-hydroxy-R-benzaldehyde-S-methylisothiosemicarbazones (R = 3-methoxy or 4-hydroxy) with the corresponding aldehydes in the presence of FeCl3 and NiCl2 yielded N1,N4-disalicylidene chelate complexes. The compounds were characterized by means of elemental and spectroscopic methods. The structure of complex 1 was determined by X-ray single crystal diffraction. Crystal data (Mo K?; 296 K) are as follows: monoclinic space group P21/c, a = 12.9857(8) Å, b = 7.8019(4) Å, c = 19.1976(12) Å, ß = 101.655(5)°, Z = 4. Cytotoxic effects of the compounds were evaluated by the MTT assay in K562 leukemia, ECV304 endothelial and normal mononuclear cells, and DNA fragmentation analysis using the diphenylamine reaction was performed. The DNA binding capacity of thiosemicarbazones at IC50 and different concentrations was investigated. The DNA fragmentation percentage of compound treated cells was higher than that of non-treated control cells but was higher for compound 3 (84%) compared to the others. The interaction of compounds 1-4 and DNA was investigated voltammetrically by using nucleic acid modified electrodes after the double stranded fish sperm DNA (fsDNA), or poly(dA)·poly(dT), was immobilized onto the surface of pencil graphite electrodes (PGEs). Accordingly, the oxidation signals of DNA bases, guanine and adenine, were measured by using differential pulse voltammetry (DPV). The changes in the signals of guanine and adenine were evaluated before and after the interaction process. The results indicated that compound 3 was cytotoxic at very low concentrations in K562 leukemia cells unlike other cells and that could damage the DNA double stranded form, specifically the adenine base. Therefore, it may have a selective antileukemic effect and drug potential. © The Royal Society of Chemistry and the Centre National de la Recherche Scientifique 2015