Oxali-palladium nanoparticle synthesis, characterization, protein binding, and apoptosis induction in colorectal cancer cells.

This paper focuses on the synthesis of nano-oxali-palladium coated with turmeric extract (PdNPs) using a green chemistry technique based on the reduction in the Pd (II) complex by phytochemicals inherent in turmeric extract. PdNPs were examined and characterized using Field Emission Scanning Electron Microscopy (FESEM), Dynamic Light Scattering (DLS), Fourier Transform Infrared (FTIR), and Atomic Force Microscopy (AFM). Using different spectroscopic and molecular dynamics simulations, a protein-binding analysis of the produced nanoparticle was conducted by observing its interaction with human serum albumin (HSA). Lastly, the cytotoxic effects and apoptotic processes of PdNPs were studied against the HCT116 human colorectal cell line using the MTT assay and flow cytometry tests. According to the findings, PdNPs with spherical and homogenous morphology and a size smaller than 100 nm were generated. In addition, they can induce apoptosis in colorectal cancer cells in a dose-dependent manner with a lower Cc50 (78 µL) than cisplatin and free oxali-palladium against HCT116 cells. The thermodynamic characteristics of protein binding of nanoparticles with HSA demonstrated that PdNPs had a great capacity for quenching and interacting with HSA through hydrophobic forces. In addition, molecular dynamics simulations revealed that free oxali-palladium and PdNP attach to the same area of HSA via non-covalent interactions. It is conceivable to indicate that the synthesized PdNPs are a potential candidate for the construction of novel, nature-based anticancer treatments with fewer side effects and a high level of eco-friendliness.

In-vitro cytotoxicity and in-vivo antitumor activity of two platinum complexes with 1,3-dimethyl pentyl glycine ligand against breast cancer.

Platinum (Pt) derivatives are good candidates for discovering new anti-tumor agents. The present research aims to explore the in-vivo and in-vitro anticancer activity of two platinum complexes with 1,3-dimethyl pentyl glycine ligand (DMPG), [Pt(bpy)(13DMPG)]NO3 and [Pt(dach)(13DMPG)]NO3, against breast cancer cells. The present study was conducted to investigate the cytotoxic potential of these compounds (2-400 µM) compared to standard drugs (cisplatin, oxaliplatin, and carboplatin) on SKBR3 cells using the methyl thiazol-tetrazolium (MTT) assay. Furthermore, the gene expression changes of Bak, Bim, Bcl-2, Caspase-3, and Caspase-9 were carried out by real-time polymerase chain reaction (PCR), and flow cytometric analysis was performed to confirm the cell apoptosis in the presence of the compounds. For more validation, in-vivo anticancer activities of both compounds were investigated against breast transplanted tumors in the BALB/c mice model. The cytotoxic studies by MTT assay revealed the anti-proliferative potential of both derivatives. [Pt(dach)(13DMPG)]NO3 with an IC50 value of 15 µM, exhibited higher cytotoxicity against SKBR3 cells as compared to [Pt(bpy)(13DMPG)]NO3, oxaliplatin, and carboplatin. Based on the flow cytometry analysis, both derivatives demonstrated apoptotic effects. Also, real-time PCR analysis revealed an up-regulation of Bak, Bim, Bax, Caspases-3, and Caspase-9 genes and a significant reduction in Bcl-2 gene expression in treated cells with both compounds compared to the control group. In-vivo results validated in-vitro analysis and showed the anticancer activity of compounds against breast transplanted tumors in the BALB/c mice model. According to the results, [Pt(dach)(13DMPG)]NO3 displayed a significant anticancer activity.

How can the cisplatin analogs with different amine act on DNA during cancer treatment theoretically?

Cisplatin is a widely used anti-cancer drug which inhibits the replication and polymerization of DNA molecule while showing some side effects and drug resistance. For this reason, to enhance its therapeutic index, researchers have synthesized several thousand analogs and tested their properties. In this project, several cisplatin analogs were designed to theoretically study the biological activity and lipophilicity effects on amine changes. The amines of the cisplatin molecule were substituted with aliphatic amines in different analogs. Computational methods such as molecular dynamics simulation, molecular docking, and molecular mechanics Poisson-Boltzmann surface area analysis were performed to investigate the binding of six cisplatin derivatives with DNA. The binding affinity and potential interactions of these drugs with double-strand DNA were analyzed. The stability effect of these drugs was investigated via root-mean-square deviation and root-mean-square fluctuation analysis, which showed that some analogs can break base-pair interaction at the end of DNA and reduced the stability of DNA. Also, the results revealed that the hydrogen bond is one of the most important factors in the binding of cisplatin's adduct to DNA. Molecular mechanics Poisson-Boltzmann surface area analysis indicated that electrostatic and van der Waals interactions are the most important deriving forces to the binding of cisplatin's drug to DNA. Finally, data revealed that cisplatin and the cis-dichloro-dimethylamine-platin tendency for binding to DNA are greater than that of other analogs.

Kinetic and Thermodynamic Investigation of Human Serum Albumin Interaction with Anticancer Glycine Derivative of Platinum Complex by Using Spectroscopic Methods and Molecular Docking.

In this paper, a new anticancer Pt (II) complex, cis-[Pt (NH3)2(tertpentylgly)]NO3, was synthesized with glycine-derivative ligand and characterized. Cytotoxicity of this water-soluble Pt complex was studied against human cancer breast cell line of MCF-7. The interaction of human serum albumin (HSA) with Pt complex was studied by using UV-Vis, fluorescence spectroscopy methods, and molecular docking at 27 and 37 °C in the physiological situation (I = 10 mM, pH = 7.4). The negative [Formula: see text] and positive [Formula: see text] indicated that electrostatic force may be a major mode in the binding between Pt complex and HSA. Binding constant values were obtained through UV-Vis and fluorescence spectroscopy that reveal strong interaction. The negative Gibbs free energy that was obtained by using the UV-Vis method offers spontaneous interaction. Fluorescence quenching the intensity of HSA by adding Pt complex confirms the static mode of interaction is effective for this binding process. Hill coefficients, nH, Hill constant, kH, complex aggregation number around HSA, , number of binding sites, g, HSA melting temperature, Tm, and Stern-Volmer constant, kSV, were also obtained. The kinetics of the interaction was studied, which showed a second-order kinetic. The results of molecular docking demonstrate the position of binding of Pt complex on HSA is the site I in the subdomain IIA.

Anticancer, antibacterial and antifungal activity of new ni (ii) and cu (ii) complexes of imidazole-phenanthroline derivatives.

Two new nickel(II) and copper(II) complexes of 2-(Furan-2-yl)-1H-Imidazo[4,5-f][1,10]Phenanthroline (FIP) and 2-(thiophen-2-yl)-1H-imidazo[4,5-f][1,10]phenanthroline (TIP), imidazophen derivatives were synthesized. The structures of the compounds were determined by UV-visible and FT-IR spectroscopic methods and elemental analysis. The biological activities of Ni and Cu complexes, as anticancer agents, were tested against chronic myelogenous leukemia cell line, K562, at micromolar concentration. The MTT studies showed Cc50 values are 21 and 160 µM for Cu and Ni(II) complexes, respectively; suggesting that Ni (II) complex has Cc50 almost seven times of that obtained for cisplatin. Biological activity of the Ni(II) and Cu(II) complexes were also assayed against selective microorganisms by disc diffusion method. These results showed that the Cu(II) complex is antifungal agent but Ni(II) complex has antibacterial activity.

DNA as a Target for Anticancer Phen-Imidazole Pd(II) Complexes.

Imidazole ring is a known structure in many natural or synthetic drug molecules and its metal complexes can interact with DNA and do the cleavage. Hence, to study the influence of the structure and size of the ligand on biological behavior of metal complexes, two water-soluble Pd(II) complexes of phen and FIP ligands (where phen is 1,10-phenanthroline and FIP is 2-(Furan-2-yl)-1H-Imidazo[4,5-f][1, 10]phenanthroline) with the formula of [Pd(phen)(FIP)](NO3)2 and [Pd(FIP)2]Cl2, that were activated against chronic myelogenous leukemia cell line, K562, were selected. Also, the interaction of these anticancer Pd(II) complexes with highly polymerized calf thymus DNA was extensively studied by means of electronic absorption, fluorescence, and circular dichroism in Tris-buffer. The results showed that the binding was positive cooperation and [Pd(phen)(FIP)](NO3)2 (K f = 127 M-1 G = 1.2) exhibited higher binding constant and number of binding sites than [Pd(FIP)2]Cl2 (K f = 13 M-1 G = 1.03) upon binding to DNA. The fluorescence data indicates that quenching effect for [Pd(phen)(FIP)](NO3)2 (K SV = 58 mM-1) was higher than [Pd(FIP)2]Cl2 (K SV = 12 mM-1). Also, [Pd(FIP)2]Cl2 interacts with ethidium bromide-DNA, as non-competitive inhibition, and can bind to DNA via groove binding and [Pd(phen)(FIP)](NO3)2 can intercalate in DNA. These results were confirmed by circular dichroism spectra. Docking data revealed that longer complexes have higher interaction energy and bind to DNA via groove binding. Graphical Abstract Two anticancer Pd(II) complexes of imidazole derivative have been synthesized and interacted with calf thymus DNA. Modes of binding have been studied by electronic absorption, fluorescence, and CD measurements. [Pd(FIP)2]Cl2 can bind to DNA via groove binding while intercalation mode of binding is observed for [Pd(phen)(FIP)](NO3)2.

Molecular dynamic simulation and spectroscopic investigation of some cytotoxic palladium(II) complexes interaction with human serum albumin.

Studies on the interactions between metallodrugs and human serum albumin (HSA), as carrier for drugs and biological molecules, are extremely important to design and discover new drugs. The interaction of three novel synthesized complexes of [Pd(phen)(R-gly)]NO3, where R-gly is methyl-, propyl-, and amyl-glycine and phen is 1,10- phenanthroline, with HSA were investigated using spectroscopic studies in combination with a molecular dynamic simulation. These water soluble complexes can denature HSA at ~50 µM. According to the results obtained for the isothermal titration at 27 and 37°C, it was found that there are 10, 8, and 6 binding sites (g) for methyl-, propyl-, and amyl-glycine complexes on the HSA with positive cooperativity in binding, respectively. Also, the binding and thermodynamic parameters were analyzed. We found a good consistency between secondary structure and simulation data with spectroscopic studies, and the experimental data are confirmed by molecular simulation results. In addition, the results related to helix, beta sheets, and coil percentages revealed that all complexes decrease the helix structure and increase the beta structure; and that the amyl derivative is more effective in denaturing the HSA structure.