A new mononuclear zinc(II) complex: Crystal structure, DNA- and BSA-binding, and molecular modeling; in vitro cytotoxicity of the Zn(II) complex and its nanocomplex.

A new mononuclear Zn(II) complex, [Zn(Me2bpy)3](PF6)2·DMF (Me2bpy = 4,4'-dimethyl-2,2'-bipyridine), has been synthesized and fully characterized. Binding studies of the Zn(II) complex with fish sperm DNA (FS-DNA) and bovine serum albumine (BSA) were investigated using cyclic voltammetry, UV-Vis and fluorescence spectroscopies. The results showed that the majority of the interaction modes between the Zn(II) complex and DNA is a combination of the electrostatic and minor groove bindings, and the microenvironment of three aromatic amino acids residues is changed due to the interaction of the Zn(II) complex with BSA. In vitro cytotoxicity studies of the Zn(II) complex and its nanocomplex against three human carcinoma cell lines (MCF-7, A-549, and HT-29) using an MTT assay indicated that the cytotoxicity of both compounds against HT-29 and MCF-7 is higher than A-549. Moreover, the results clearly demonstrated that the aqueous colloid of the Zn(II) nanocomplex is more effective than the complex solution against HT-29 and MCF-7 cells under the same experimental conditions. The microscopic analyses of the cancer cells showed that the Zn(II) complex apparently induces the cell apoptosis. The interactions of the Zn(II) complex with DNA and BSA were also modeled using molecular docking. The results are in good agreement with the experimental findings.

Spectroscopic, biological, and molecular modeling studies on the interactions of [Fe(III)-meloxicam] with G-quadruplex DNA and investigation of its release from bovine serum albumin (BSA) nanoparticles.

The guanine-rich sequence, specifically in DNA, telomeric DNA, is a potential target of anticancer drugs. In this work, a mononuclear Fe(III) complex containing two meloxicam ligands was synthesized as a G-quadruplex stabilizer. The interaction between the Fe(III) complex and G-quadruplex with sequence of 5'-G3(T2AG3)3-3' (HTG21) was investigated using spectroscopic methods, molecular modeling, and polymerase chain reaction (PCR) assays. The spectroscopic methods of UV-vis, fluorescence, and circular dichroism showed that the metal complex can effectively induce and stabilize G-quadruplex structure in the G-rich 21-mer sequence. Also, the binding constant between the Fe(III) complex and G-quadruplex was measured by these methods and it was found to be 4.53(±0.30) × 10(5) M(-1)). The PCR stop assay indicated that the Fe(III) complex inhibits DNA amplification. The cell viability assay showed that the complex has significant antitumor activities against Hela cells. According to the UV-vis results, the interaction of the Fe(III) complex with duplex DNA is an order of magnitude lower than G-quadruplex. Furthermore, the release of the complex incorporated in bovine serum albumin nanoparticles was also investigated in physiological conditions. The release of the complex followed a bi-phasic release pattern with high and low releasing rates at the first and second phases, respectively. Also, in order to obtain the binding mode of the Fe(III) complex with G-quadruplex, molecular modeling was performed. The molecular docking results showed that the Fe(III) complex was docked to the end-stacked of the G-quadruplex with a π-π interaction, created between the meloxicam ligand and the guanine bases of the G-quadruplex.

A mononuclear zinc(II) complex with piroxicam: crystal structure, DNA- and BSA-binding studies; in vitro cell cytotoxicity and molecular modeling of oxicam complexes.

A new mononuclear Zn(II) complex, trans-[Zn(Pir)2(DMSO)2], where Pir(-) is 4-hydroxy-2-methyl-N-2-pyridyl-2H-1,2-benzothiazine-3-carboxamide-1,1-dioxide (piroxicam), has been synthesized and characterized. The crystal structure of the complex was obtained by the single crystal X-ray diffraction technique. The interaction of the complex with DNA and BSA was investigated. The complex interacts with FS-DNA by two binding modes, viz., electrostatic and groove binding (major and minor). The microenvironment and the secondary structure of BSA are changed in the presence of the complex. The anticancer effects of the seven complexes of oxicam family were also determined on the human K562 cell lines and the results showed reasonable cytotoxicities. The interactions of the oxicam complexes with BSA and DNA were modeled by molecular docking and molecular dynamic simulation methods.

Experimental and molecular modeling studies on the interaction of the Ru(II)-piroxicam with DNA and BSA.

A mononuclear Ru(II) complex containing two piroxicam (Pir(-)) ligands was synthesized and fully characterized. Interaction studies of the Pir(-) anion and the Ru(II) complex with DNA and BSA were carried out using spectroscopic techniques. The results suggested that the Pir(-) anion binds to DNA in a moderately strong fashion via intercalation between the base stacks of double-stranded DNA, while the Ru(II) complex is a groove binder and interacts with DNA with more affinity. Moreover, the results demonstrated that the microenvironment and the secondary structure of BSA were changed in the presence of Pir(‾) and Ru(II) complex. The free Pir(‾) ligand and the Ru(II) complex can lead to the photocleavage of DNA supercoiled pUC57. Finally, the binding of the Ru(II) complex to BSA and DNA was modeled by molecular docking and molecular dynamic simulation methods.