Structural Characterization, Antimicrobial Activity and BSA/DNA Binding Affinity of New Silver(I) Complexes with Thianthrene and 1,8-Naphthyridine.

Three new silver(I) complexes [Ag(NO3)(tia)(H2O)]n (Ag1), [Ag(CF3SO3)(1,8-naph)]n (Ag2) and [Ag2(1,8-naph)2(H2O)1.2](PF6)2 (Ag3), where tia is thianthrene and 1,8-naph is 1,8-naphthyridine, were synthesized and structurally characterized by different spectroscopic and electrochemical methods and their crystal structures were determined by single-crystal X-ray diffraction analysis. Their antimicrobial potential was evaluated against four bacterial and three Candida species, and the obtained results revealed that these complexes showed significant activity toward the Gram-positive Staphylococcus aureus, Gram-negative Pseudomonas aeruginosa and the investigated Candida species with minimal inhibitory concentration (MIC) values in the range 1.56-7.81 µg/mL. On the other hand, tia and 1,8-naph ligands were not active against the investigated strains, suggesting that their complexation with Ag(I) ion results in the formation of antimicrobial compounds. Moreover, low toxicity of the complexes was detected by in vivo model Caenorhabditis elegans. The interaction of the complexes with calf thymus DNA (ct-DNA) and bovine serum albumin (BSA) was studied to evaluate their binding affinity towards these biomolecules for possible insights into the mode of antimicrobial activity. The binding affinity of Ag1-3 to BSA was higher than that for DNA, indicating that proteins could be more favorable binding sites for these complexes in comparison to the nucleic acids.

Three water-soluble acylhydrazone tetranuclear transition metal complexes: Crystal structures, DNA/BSA interactions and cytotoxicity studies.

2-acetylpyridine-4-chloropyridine-2­carbonyl hydrazone (C13H11ClN4O, HL) and its three water-soluble tetranuclear complexes [Cu4(NO3)2(L)4]·(NO3)2 (1), [Co4(NO3)2(H2O)(C2H5OH)(L)4]·(NO3)2 (2) and [Zn4(NO3)2(H2O)(C2H5OH)(L)4]·(NO3)2 (3) were synthesized and characterized showing that 1-3 were all tetranuclear complexes. The interactions of HL, 1-3 with calf thymus DNA (CT-DNA) and bovine serum albumin (BSA) were explored using ultraviolet-visible (UV-Vis) titration, fluorescence spectroscopy, microcalorimetry and molecular docking techniques. The UV-Vis spectroscopy measurements showed that complexes 1-3 could strongly bind to CT-DNA by the intercalation mode, while HL interacted with CT-DNA through groove binding. From the fluorescence spectroscopy results, the interaction between HL, 1-3 and BSA was a static quenching procedure, in which complexes 1-3 had two binding sites near Trp residues of BSA while HL only had one. The microcalorimetric studies revealed that the interactions of HL and 1-3 to CT-DNA/BSA were all endothermic and the duration of each interaction was all less than 30 min. The in silico molecular docking illustrated intermolecular interactions of 1-3 binding with DNA/BSA included hydrogen bond, halogen bond, hydrophobic and electrostatic interactions. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay indicated that complex 1 possessed better cytotoxicity against HeLa, A549, MCF7 and HCT-116 than cisplatin and could be used as an alternative anticancer drug.

Synthesis, DNA/BSA binding studies and in vitro biological assay of nickel(II) complexes incorporating tridentate aroylhydrazone and triphenylphosphine ligands.

Two new nickel (II) triphenylphosphine complexes derived from tridentate aroylhydrazone ligands [H2L1 = 2-hydroxy-3-methoxybenzylidene)benzohydrazone and H2L2 = N'-(2-hydroxy-3-methoxybenzylidene)-2-hydroxybenzoylhydrazone] and triphenylphosphine were prepared and their molecular structures were determined by single crystal X-ray diffraction analysis. Both nickel(II) complexes showed slightly distorted square planar geometry with one tridentate aroylhydrazone ligand coordinated through ONO donor atoms and one triphenylphosphine ligand coordinated to the nickel center through the phosphorus atom. DNA interaction studies indicated that both complexes possessed higher affinity to herring sperm DNA (HS-DNA) than the corresponding free aroylhydrazone ligand. Molecular docking investigations showed that both complexes could bind to DNA through intercalation of the phenyl rings between adjacent base pairs in the double helix. Meanwhile, bovine serum albumin (BSA) binding studies revealed the complexes could effectively interact with BSA and change the secondary structure of BSA. Further pharmacological evaluations of the synthesized complexes by in vitro antioxidant assays demonstrated high antioxidant activity against NO· and O2˙- radicals. The anticancer activity of each complex was assessed through in vitro cytotoxicity assays (CCK-8 kit) toward A549 and MCF-7 cancer cell and normal L-02 cell lines. Significantly, the Ni(II) complex derived from H2L1 ligand was found to be more effective cytotoxic toward MCF-7cancerous cell with the IC50 value equaled 9.7 µM, which showed potent cytotoxic activity over standard drug cisplatin. AbbreviationsA549human lung carcinoma cellBSAbovine serum albuminCCK-8Cell Counting Kit-8DFTdensity functional theoryDNAdeoxyribonucleic acidDPPH˙2,2-diphenyl-1-picrylhydrazylH2L12-hydroxy-3-methoxybenzylidene)benzohydrazone N'-(2-hydroxy-3-methoxybenzylidene)-2-hydroxybenzoylhydrazoneH2L2N'-(2-hydroxy-3-methoxybenzylidene)-2-hydroxybenzoylhydrazoneHOMOhighest occupied molecular orbitalIC50the 50% activityL-02human normal liver cellLOMOlowest unoccupied molecular orbital (LUMO)MCF-7human breast carcinoma cellNO˙nitric oxideO2˙-superoxide anionSODsuperoxide dismutaseCommunicated by Ramaswamy H. Sarma.