Effect of geometric isomerism on the anticancer property of new platinum complexes with glycine derivatives as asymmetric N, O donate ligands against human cancer.

In this project, to fallow the anticancer ability of new Pt drugs, several new Pt complexes were synthesized with the asymmetric bidentate glycine derivatives, as named propyl- and hexyl glycine (L), in the general formula: [Pt(NH3)2(L)]NO3, and cis- and trans-[Pt(L)2]. The structure of two cis- and trans-[Pt(propylgly)2] complexes was proved by single crystallography analysis. However, all complex structures were characterized by various methods of 1H NMR, 13C NMR, 195Pt NMR, FTIR, LC-Mass, and Raman spectroscopy. To study the passage of water-soluble complexes of [Pt(NH3)2(L)]NO3 via cell membrane, their solubility, and lipophilicity were analyzed. In addition, the cytotoxic properties of these complexes were evaluated against normal and malignant cell lines (skin, breast, and lung cancer cells). The results indicated that they were either comparable to cisplatin or less damaging than carboplatin and oxaliplatin. It was expected that due to less steric effect, and the presence of length aliphatic hydrocarbon chain in the complex structure, trans-[Pt(hexylgly)2] is more toxic on cancerous cell lines than trans-[Pt(propylgly)2]. Cellular accumulation of all complexes was evaluated on A549 and MCF7 cell lines, and the amount of platinum metal (ng) was measured by the ICP method. Results showed that trans-[Pt(hexylgly)2] complex has the highest accumulation inside both mentioned cell lines and [Pt(NH3)2(L)]NO3 complexes behave like clinical Pt-drugs. Ultimately, the interaction patterns of DNA were examined using spectroscopic methods and molecular docking simulations for all substances.

Structure-bioactivity relationship study on anticancer Pd and Pt complexes with aliphatic glycine derivative ligands.

To investigate the structure and bioactivity relationship, six Pd(II)/Pt(II) complexes with N-isobutylglycine (L1) and cyclohexylglycine (L2) as N^O amino acid bidentate ligands, 1,10'-phenanthroline (phen) and 2,2'-bipyridine (bipy) as N^N donor ligands, and [Pd(L1)(bipy)]NO3 (1), [Pd(L2)(bipy)]NO3 (2), [Pd(L1)(phen)]NO3 (3), [Pd(L2)(phen)]NO3·2H2O (4), [Pt(L1)(phen)]NO3 (5), along with [Pt(L2)(phen)]NO3 (6) were prepared and then characterized. The geometry of each compound was validated by doing a DFT calculation. Furthermore, tests were conducted on the complexes' water solubilities and lipophilicity. All bipy complexes had superior aqueous solubility and less lipophilicity in comparison with phen complexes, as well as complexes containing cyclohexyl-glycine compared to isobutyl-glycine complexes, probably because of the steric effects and polarity of cyclohexylglycine. The in-vitro anticancer activities of these compounds were examined against HCT116, A549, and MCF7 cancerous cell lines. Data revealed that all Pd/Pt complexes demonstrate higher anticancer activity than carboplatin, and complexes 3 and 4 are more cytotoxic than cisplatin against the HCT116 cell line, particularly against MCF7 cancerous cells. In addition, among all compounds, complex 4 has more anticancer ability than oxaliplatin. Due to different solubility and lipophilicity behavior, the accumulation of Pt complexes and clinical Pt drugs in each cancerous cell was investigated. The binding capabilities of these complexes to DNA, as the main target in chemotherapy, occur through minor grooves and intercalate into DNA, which was done using absorption, fluorescence, and circular dichroism spectroscopy. Finally, the docking simulation study showed the mode of DNA bindings is in good agreement with the spectral binding data.

Unraveling the binding interactions between two Pt(II) complexes of aliphatic glycine derivatives with human serum albumin: A comprehensive computational and multi-spectral investigation.

This article delves into the interaction between HSA protein and synthesized platinum complexes, with formula: [Pt(Propyl-NH2)2(Propylglycine)]NO3 and [Pt(Tertpentyl-NH2)2(Tertpentylglycine)]NO3, through a range of methods, including spectroscopic (UV-visible, fluorescence, synchronous fluorescence and CD) analysis and computational modeling (molecular docking and MD simulation). The binding constants, the number of binding sites, and thermodynamic parameters were obtained at 25 to 37 °C. The study found that both complexes could bind with HSA (moderate affinity for Tertpentyl and strong affinity for Propyl derivatives) and occupied one binding site in HSA (validated with, Stern-Volmer, Job-plots, and molecular docking investigations) located in subdomain IIA. The binding mechanisms of both mentioned Pt(II) agents were different, with the Propyl derivative predominantly using van der Waals forces and hydrogen bond interactions with a static quenching mechanism and the Tertpentyl derivative mainly utilizing hydrophobic force with a dynamic quenching mechanism. However, the two ligands affected protein differently; the Tertpentyl complex did not significantly alter the protein structure upon binding, as evidenced by synchronous fluorescence spectroscopy (SFS), CD spectroscopy, and MD analysis. The outcome helps in understanding the binding mechanisms and structural modifications induced by the ligands, which could aid in the innovation of more effective and stable Pt(II)-based drugs.

Spectroscopic study and molecular simulation: Bovine serum albumin binding with anticancer Pt complex of amyl dithiocarbamate ligand.

Until now, many methods have been proposed to treat cancer, such as radiation therapy and drug therapy, but none of them have caused a complete cure for cancer. Heavy metal complexes such as cisplatin are among the compounds used as drugs in chemotherapy against cancer cells. These compounds cause cell death and have anti-cancer properties, but they have side effects. The biochemical mechanism of cisplatin is related to its interaction with DNA through covalent binding. To reduce the toxicity of metallodrugs, new complexes can be designed containing S, S- bidentate ligands such as diethyldithiocarbamate. Moreover, anti-cancer compounds probably interact with proteins, such as HSA, before passing the cancerous cell membrane and DNA as a target. So, the function of proteins and their stabilities are expected to change. In this research, the mode of binding of [Pt (bpy) (amyl.dtc)]NO3 complex with BSA was evaluated by various thermodynamic methods. Negative binding enthalpy and entropy changes amounts show that the connection between the Platinum compound and BSA occurs via the van Der Waals type of hydrogen bond. The negative Gibbs free energy change was obtained through isothermal titration, which showed interaction proceeds spontaneously. Moreover, the emission titration data showed that protein fluorescence quenching by platinum agent titration is static. Binding, quenching constants, and binding site number were obtained by the Stern-Volmer equation, and only one binding site was determined for this interaction. A Scatchard plot with a positive slope shows the Pt agent-BSA formation is proceeding positively cooperative. The kinetic study displayed that the absorption monitoring followed the second-order model. Finally, molecular docking simulation showed that the position of the Pt agent on protein is placed I under region II.

Green Synthesis and Bioactivity of Aliphatic N-Substituted Glycine Derivatives.

Standard amino acids have an asymmetric α-carbon atom to which -COOH, -NH2, -H, and -R groups are bonded. Among them, glycine is the simplest (R = -H) with no asymmetric carbon, and other natural amino acids are C-substituted of glycine. Here, we have designed and made a green synthesis of some new N-substituted glycine derivatives with R-(NH)CH2-COOH formula, where R is flexible and hydrophobic with different chain lengths and benches of the type propyl, butyl, sec-butyl, tert-butyl, pentyl, isopentyl, tert-pentyl, hexyl, 2-aminoheptyl, and octyl. These glycine derivatives were characterized by recording their melting points and FT-IR, mass, 1H NMR, and 13C NMR spectra. DFT studies revealed that 2-aminoheptyl glycine had the highest electronegativity value and can thus act as a good bidentate ligand for the metal centers. ADME comparative results and bioavailability radars indicated that both octyl- and 2-aminoheptyl glycine had the most lipophilicity, making them good agents in cell passing. Furthermore, lipophilicity determination showed that octyl glycine was the best and propylgly was more soluble than others. Based on solubility, lipophilicity, and dipole moment values, propyl- and 2-aminoheptyl-glycine were considered for bio-macromolecular interaction studies. Thus, the interaction of these two agents with DNA and HSA was studied using absorption spectroscopy and circular dichroism techniques. Due to the presence of the R-amine group, they can interact with the DNA by H-binding and hydrophobicity, while electrostatic mode could not be ruled out. Meanwhile, molecular docking studies revealed that octyl- and 2-aminoheptyl glycine had the highest negative docking energy, which reflects their higher tendency to interact with DNA. The DNA binding affinity of two candidate AAs was determined by viscosity measurement and fluorescence emission recording, which confirms that groove binding occurs. Also, the toxicity of these synthesized amino acid derivates was tested against the human foreskin fibroblast (HFF) cell line. They showed IC50 values within the range of 127-344 µM after 48 h with the highest toxicity for 2-aminoheptyl glycine.

Platinum (II) complex of isopentyl glycine ligand: DNA binding, molecular dynamic, and anticancer activity against breast cancer.

In this paper, we performed thorough experimental and theoretical calculations to examine the interaction between Pt derivative, as an anticancer, and ct-DNA. The mode of DNA binding with [Pt(NH3)2(Isopentylgly)]NO3, where Isopentylgly is Isopentyl glycine, was evaluated by various spectroscopic methods, docking, and molecular dynamics simulation studies. UV-Vis and fluorescence spectroscopic titration results and CD spectra of DNA-drug showed this interaction is via groove binding. Also, thermal stability studies or DNA melting temperature changes (ΔTm), as well as the quenching emissions monitoring proved it. Also, the thermodynamic parameter and binding constant displayed that complex-DNA formation is a spontaneous process, and H-binding and also groove binding were found to be the main forces. Theoretical studies stated [Pt(NH3)2(Isopentylgly)]NO3-DNA formation occurs on C-G center on DNA, along with rising DNA-compound stability. IC50 value against the human breast cell line probably is due to the Isopentyl glycine ligand in the structure of the Pt compound, and it was obtained more than cisplatin and less than carboplatin against the MCF7 cell.Communicated by Ramaswamy H. Sarma.

Biological interaction of Pt complex with imidazole derivative as an anticancer compound with DNA: Experimental and theoretical studies.

This investigation is applied to find out interesting information on DNA binding mode with Pt(II) derivative of two N, N bidentate ligands in treating cancer. Thus, one new water-soluble platinum complex with FIP and phen with a new formula of [Pt(phen)(FIP)](NO3)2 was prepared and specified. DFT data can be used to evaluate geometry parameters. Based on the ADMET prediction, this complex can be considered a drug-like agent. Cytotoxicity property was evaluated against some human cancerous MCF7, A549, and HCT116 cell lines. Accumulation of Pt complex, cisplatin, and oxaliplatin in each cancerous cell was determined, which is probably related to their lipophilicity and solubility properties. The binding mode of the complex to ct-DNA was investigated by fluorescence spectroscopy, circular dichroism, and molecular docking simulation. The viscosity of DNA by different concentrations of EB and Pt complex titration shows Pt complex interacts with DNA via groove binding like the spectroscopic binding result. In the MD study, DNA helix, RMSD, and RMSF analysis showed that DNA stability decreased and that the majority of residues left the initial state. DNA increased residual deviations and flexibility are linked to an increase in its gyratory radius, which is consistent with the findings of the experiments.

New platinum (II) complexes based on schiff bases: synthesis, specification, X-ray structure, ADMET, DFT, molecular docking, and anticancer activity against breast cancer.

Acylpyrazolone-based Schiff base ligands (HLn) and their corresponding Pt(II) complexes with the general formula [Pt(Ln)(Cl)] (n = 1-3) were synthesized and characterized by different spectroscopic techniques including 1H-NMR, 195Pt-NMR, LC-Mass, FT-IR, and UV-Vis spectroscopy, as well as elemental analysis. The crystal structure of one of the Schiff base ligands was also obtained. Based on the ADMET comparative results and the bioavailability radar charts, the complexes are completely drug-like. The Schiff base complexes with a structural difference of one methyl group in ligand were used as anticancer agents against human breast cancer cell lines SKBR3 and MDA-MB-231. The IC50 values after treatment by [Pt(L1)Cl] and [Pt(L2)Cl] were obtained more than cisplatin and less than carboplatin on cancer cells MDA-MB-231 and SKBR3, while the IC50 value of [Pt(L3)Cl] was more than both other complexes and clinical Pt drugs. Molecular docking data showed that the groove binding is the main interaction with DNA double strands with a minor contribution from electrostatic interactions. To investigate the structure-activity relationship, DFT computational was done. All quantum chemical parameters display the drug approaching biomacromolecule and more biological activity of [Pt(L1)Cl] > [Pt(L2)Cl] > [Pt(L3)Cl]. So, three Schiff base platinum complexes can be suitable candidates as anticancer drugs. Schiff-base ligands (HLn) and their Pt(II) complexes ([Pt(Ln)(Cl)], n=1-3) were obtained. To investigate their biological property and main interactions with DNA, ADMET, and cytotoxicity against MDA-MB-231 and SKBR3, DFT, and Molecular docking were done.

High cancer selectivity and improving drug release from mesoporous silica nanoparticles in the presence of human serum albumin in cisplatin, carboplatin, oxaliplatin, and oxalipalladium treatment.

In this project, drug release was examined based on the adsorption of cisplatin, carboplatin, oxaliplatin, and oxalipalladium on aminated mesoporous silica nanoparticles (N-HMSNs) and human serum albumin (HSA). These compounds were characterized by different techniques where three clinical Pt-drugs, cisplatin, carboplatin, oxaliplatin, plus oxalipalladium were loaded and investigated for release. Based on loading analysis, the loading ability of the mentioned metallodrug on N-HMSNs was dependent on the nature of the drug structure as well as hydrophobic or hydrophilic interactions. Different adsorption and release profiles were observed for all mentioned compounds via dialysis and ICP method analysis. Although the maximum to minimum loading occurred for oxalipalladium, cisplatin, and oxaliplatin to carboplatin, respectively, release from a surface with greater control belonged to carboplatin to cisplatin systems in the absence and presence of HSA to 48 h due to weak interaction for carboplatin drug. The quick release of all mentioned compounds from the protein level at high doses of the drug during chemotherapy occurred very fast within the first 6 h. In addition, the cytotoxic activity of both free drugs and drug-loaded@N-HMSNs samples on cancerous MCF-7, HCT116, A549, and normal HFF cell lines was evaluated by MTT assay. It was found that free metallodrugs exhibited more active cytotoxic behavior on both cancerous and normal cell lines than drug-loaded@N-HMSNs. Data demonstrated that the Cisplatin@N-HMSNs with SI=6.0 and 6.6 for MCF7 and HCT116 cell lines, respectively, and Oxaliplatin@N-HMSNs with SI=7.4 for HCT116 cell line can be good candidates as an anticancer drug with minimal side effects by protecting cytotoxic drugs as well as controlled release and high selectivity.

Spectroscopy and molecular dynamic study of the interaction of calf thymus DNA by anticancer Pt complex with butyl glycine ligand.

Despite the past few decades since the discovery of anticancer drugs, there is still no definitive treatment for its treatment. Cisplatin is a chemotherapy medication used to treat some cancers. In this research, the DNA binding affinity of Pt complex with butyl glycine ligand was studied by various spectroscopy methods and simulation studies. Fluorescence and UV-Vis spectroscopic data showed groove binding in ct-DNA-[Pt(NH3)2(butylgly)]NO3 complex formation by the spontaneous process. The results were also confirmed by small changes in CD spectra and thermal study (Tm), as well as the quenching emission of [Pt(NH3)2(butylgly)]NO3 complex on DNA. Finally, thermodynamic and binding parameters displayed that hydrophobic forces are the main forces. Based on docking simulation, [Pt(NH3)2(butylgly)]NO3 could bind to DNA and via minor groove binding on C-G center on DNA, formed a stable DNA complex.

Biological Activity of Two Anticancer Pt Complexes with a Cyclohexylglycine Ligand against a Colon Cancer Cell Line: Theoretical and Experimental Study.

Because of their extraordinary ability to disrupt the natural structure of nucleic acids, metal complexes could be used in cancer therapy. In this study, cyclohexylglycine (HL) as a ligand and two new Pt complexes, [Pt(NH3)2(L)]NO3 (1) and [Pt(bipy)(L)]NO3 (2), were synthesized and characterized by elemental analysis, LC-MS, UV-vis spectrometry, FT-IR, 1H NMR spectroscopy, 13C NMR spectroscopy, 195Pt NMR spectroscopy, HPLC analysis, and single-crystal X-ray diffraction. Complex 2 crystallized in the orthorhombic Pbca space group, and density functional theory (DFT) was used to describe its structural parameters were described in detail. These complexes can be classified as oral medications and drug-like molecules based on a comparison of their absorption, distribution, metabolism, and excretion assessment. Quantum chemical descriptors (QCDs) were determined using DFT calculations to predict the tendency of DNA to approach these complexes. During the determination of the function of the metallodrug in DNA binding, the fluorescence data indicated that static quenching took place for all ligands and complexes with higher DNA binding affinity. CD and isothermal absorption studies indicate the presence of electrostatic and groove binding for the amine derivative and that DNA binds with the bipy moiety via groove binding. Furthermore, the interaction modes were determined using molecular docking to investigate the binding of these compounds with the target DNA molecule. According to docking investigations, binding energies of -5.7, -11.56, and -10.00 kcal/mol for HL and complexes 1 and 2, respectively, indicate partially electrostatic and groove binding. The anticancer activities of the Pt(II) complexes were tested against the HCT116 human colon cancer cell line, with IC50 values of 35.51 and 51.33 µM for 1 and 2, respectively, after 72 h. These values show that the inhibitory effect of complex 1 was better than those of 2 and carboplatin (IC50 = 51.94 µM).

Property evaluation of two anticancer candidate platinum complexes with N-isobutyl glycine ligand against human colon cancer.

Small molecules have potential usage in cancer therapy due to their remarkable potency of disarranging the natural structure of nucleic acids. In this study, two complexes [Pt(NH3)2(IBgly)]NO3 (1) and [Pt(bipy)(IBgly)]NO3 (2) based on Pt(II), N-isobutylglycine (IBgly), 2,2'-bipyridine, and ammonia were prepared and characterized by spectroscopic methods. Pharmacokinetic ADME data, absorption, distribution, metabolism, excretion, and bioavailability radar showed two complexes can be introduced for Pt-based anti-cancer drugs. Mechanism of tumor inhibition and DNA interaction of these compounds was studied by UV-Vis, fluorescence, and CD spectroscopies. Also, thermodynamic parameters and the binding constants were calculated through absorption measurements. The fluorescence data showed that a static quenching mechanism occurred for both complexes with a binding constant and binding affinity towards DNA (Kb ≈ 3500 M-1 and kq ≈ 2.1 × 1011 M-1 s-1). The thermodynamic parameters indicated electrostatic approaching and groove binding were more feasible than intercalation mode between Pt(II) complexes and DNA. CD spectra indicated the increasing intensity of the positive band and the negative band decreasing. Density functional theory calculations confirmed the experimental data and determined the quantum chemical descriptors including total energy, hardness, chemical potential, electrophilicity, electronegativity, etc. According to this, the binding tendency of these compounds with DNA could be predicted. Further, molecular docking studies were also performed. Docking studies revealed that the desolvation, hydrogen, and electrostatic binding were effective for the interaction between complexes and DNA with binding energy (- 10.44 and - 9.57 kcal/mol) for complexes 1 and 2, respectively, which is mainly of partially electrostatic and groove binding type. The cytotoxic activity of Pt complexes was examined against human colon cancer cell line which indicated good activity with IC50 values of (41.66 and 47.30 µM) for both complexes after 72 h, respectively. Also, they demonstrated more inhibitory effects compared to carboplatin.

New anticancer Pd and Pt complexes of tertamyl dithiocarbamate and DACH ligands against HT29 and Panc1 cell lines.

To investigate the reduction of side effects of commercial antitumor drugs such as cisplatin, two new platinum and palladium complexes with a formula of [M(DACH)(tertamyl.dtc)]NO3 were synthesized (DACH is 1R, 2R-diaminocyclohexane, tertamyl-dtc is tertpentyl dithiocarbamate, and M is palladium or platin ionic metals) and characterized by spectroscopic methods. The in vitro cytotoxicity of these compounds against HT29 and Panc1 cell lines showed that the IC50 values against Panc1 cell line of [Pt(DACH)(tertamyl.dtc)]NO3 and [Pd(DACH)(tertamyl.dtc)]NO3 were 263.1 and 198.7 µM, and also against HT29 cell line were 241.9 and 258.2 µM, respectively. They were similar to the value obtained for oxaliplatin and lower than cisplatin value. Thermal stability and circular dichroism results demonstrated that both metal complexes could bind to DNA via electrostatic bonds. Due to electrostatic interaction, the configuration of B-DNA to C-DNA changed, though the possibility of groove interaction may be strengthened. Furthermore, molecular docking simulation showed higher negative docking energy for [Pd(DACH)(tertamyl.dtc)]NO3 complex with a higher tendency for DNA interaction. In vitro cytotoxicity of two new Pt and Pd compounds have been studied against two cell lines (HT29 and Panc 1), which are almost equal to the value obtained for oxaliplatin and they are lower than cisplatin value. Thermal stability studies and CD results demonstrated that both complexes bind to DNA via electrostatic bonds. Further, molecular docking showed higher negative docking energy for [Pd(DACH)(tertamyl.dtc)]NO3 complex with a higher tendency for interaction.Communicated by Ramaswamy H. Sarma.

Investigating the anticancer properties of the two new platinum complexes with iso- and tert-pentylglycine by the DFT, molecular docking, and ADMET assessment and experimental confirmations.

In this study, two new anticancer platinum complexes formulated as [Pt(bpy)(L)]NO3 were synthesized using the iso and tert-pentylglycine ligands, two structural isomer ligands, to investigate side branches effect on the complex-DNA interaction. According to the comparative results of the ADMET assessment, these compounds can be considered as the drug-like molecules and oral medication. Mechanism of tumor inhibition and DNA binding parameters indicated the higher ability of the tert-isomer and also, both complexes acted through the disruption of the base pairs and stacks of helicity by the endothermic process. Fluorescence spectroscopy showed that the quenching mechanism is static for both drugs with large binding constant and high binding affinity towards the DNA. Also, the amount of binding constant of the tert -isomer was about 14 times of another structural isomerous complex. CD spectra indicated the conversion of the B-DNA into A-DNA form via electrostatic interaction for positively charged complexes. The cytotoxic data showed that both compounds have antiproliferative effects against the MCF-7 cell line and the inhibitory effect of the iso-derivative was better than the tert-one. Docking studies showed that the desolvation energy and hydrogen bond are more effective between the other interactions. The torsional free energy for both complexes mainly provided the groove binding along with partially electrostatic and intercalate binding. According to the density-functional theory data and because of positive electron density on the surface of complexes and facilitating of the metal drug to DNA phosphate groups approaching, both complexes may be good candidates for the anticancer drugs. Two new anticancer Pt(II) complexes were synthesized with glycine derivatives. In vitro cytotoxicity effects were tested against the human breast cancer cell line of MCF-7. Moreover, the modes of DNA binding with synthesized compounds were investigated using ADME prediction, DFT, molecular docking and spectroscopic methods.

Spectroscopic and docking molecular study of new anticancer Pt complex binding with human serum albumin.

After synthesizing and identifying the nature of the new complex based on platinum metal, [Pt(NH3)2(butylgly)]NO3, the interaction of this complex with human serum albumin (HSA) was performed by spectroscopy and molecular docking methods at two temperatures of 27 and 37 °C and under physiological conditions of the body. The toxicity test of this complex was performed on the MCF-7 cell line (IC50 = 300 µM). Enthalpy, entropy, Gibbs free energy, binding constant, number of complex binding sites on the HSA, Scatchard diagrams, Hill coefficient, and Hill constant were calculated and then plotted via UV/Vis. According to the Gibbs free energy obtained at two temperatures of 27 and 37 °C (-20.6, -21.2 kJ mol-1), the interaction was done spontaneously. Moreover, the melting temperature of human serum albumin with this complex; and the kinetics of this interaction (the second-order) were calculated. Using fluorescence at three temperatures of 25, 27, and 37 °C, the binding constant (2.9 × 104, 1.0 × 104, and 5.7 × 103 M-1), the quenching constant, average aggregation number of HSA, and the number of binding sites of the complex on the protein were obtained. As well, the static quenching mechanism was also observed. Molecular docking results showed that the site of binding of this complex to the HSA, is the site II subdomain IIIA, and the hydrogen and hydrophobic bonds are superior.

Two new oral candidates as anticancer platinum complexes of 1,3-dimethyl pentyl glycine ligand as doping agents against breast cancer.

1,3-Dimethylpentylamine (Geranamine) with a similar structure to amphetamine has been used as an athletic performance promoter (doping agent) and also as an indirect sympathomimetic drug to synthesize of 1,3-dimethyl pentyl glycine (13DMPG). Thereafter, two new anticancer platinum complexes as [Pt(DACH)(13DMPG)]NO3 and [Pt(bpy)(13DMPG)]NO3 were synthesized using this ligand and then characterized by spectroscopic methods. ADMET comparative results indicated that they are entirely in the pink area of the Bioavailability Radar, so they can be considered as drug-like and oral medications. Mechanism of tumor inhibition and DNA binding parameters were investigated and the results indicated the higher ability of [Pt(bpy)(13DMPG)]NO3 with the endothermic process for both systems compared with [Pt(DACH)(13DMPG)]NO3. Fluorescence study showed that the quenching mechanism is static for both drugs with large binding constant and high binding (Kb ≈ 8000 M-1 and kq ≈ 5.3 × 1011 M-1 s-1) affinity towards DNA. CD spectra showed the increased intensity of the positive band and the decreased negative band, meaning B-DNA converting to A-DNA form via electrostatic interaction for positively charged complexes. The cytotoxic effect analyzed by MTT assay showed that both compounds have effective antiproliferative on MCF-7 cell line. In addition, the inhibition effect of [Pt(DACH)(13DMPG)]NO3 (IC50 = 17 µM) was shown to be better than [Pt(bpy)(13DMPG)]NO3 (IC50 = 45 µM). According to DFT results, anticancer properties of [Pt(bpy)(13DMPG)]NO3 mainly is more than cisplatin and [Pt(DACH)(13DMPG)]NO3. Docking studies showed that the desolvation energy and hydrogen bond are more effective compared to the other interactions. The torsional free energy, about +1.19 kcal/mol, for both complexes mainly provides groove binding with partially electrostatic and intercalate bindings.

New Bi2MoO6 nano-shapes toward ultrasensitive enzymeless glucose tracing: Synergetic effect of the Bi-Mo association.

In a novel approach, an efficient non-enzymatic glucose sensor based on pure phase of aurivillius bismuth molybdate (BM or γ-Bi2MoO6) mixed metal oxides is reported. Three BM samples were synthesized, with/without l-cysteine (Cys) and dodecylamine (DDA) as additives, leading to different shapes: bullet (BM-C), confetti (BM-2Cys) and candy (BM-2DDA). The morphology and purity of the structures were confirmed by FE-SEM images and XRD. In order to investigate the sensor application, the samples were integrated on reduced graphene oxide and incorporated into simple and inexpensive glassy carbon electrode (GCE) without using any polyvinylpyrrolidone (PVP) or Nafion. To perform cyclic voltammetry experiments, all three biosensors were measured in PBS solution (pH = 7) in ±1.5 voltage range and 50 mV s-1 scan rate. Glucose identification by the synthesized composites is an obvious sign of their high efficiency. According to chronoamperomograms, the best sensitivity of 3050 µA L mmol-1 cm-2 with linear range of 0.02-0.14 mmol L-1, low detection limit (LOD) of 0.004 mmol L-1 and the signal/noise equal to 3 was achieved by BM-2DDA/rGO/GCE biosensor and its speedy amperometric response is less than 5 s. This biosensor showed impressive selectivity, repeatability and reproducibility results besides it maintains its stability considerably in great percentage of 98.5% after eight weeks. Also it showed prolonged stability after 50 min.

Some new anticancer platinum complexes of dithiocarbamate derivatives against human colorectal and pancreatic cell lines.

Cisplatin, carboplatin and oxaliplatin and their analogs are effective anticancer agents, but their clinical using is limited by some serious side effects. S,S donor ligands such as dithiocarbamates can be used to reduce some side effects. In this study, some novel water soluble complexes with formula of [Pt(bpy)(R.dtc)]NO3, where bpy is bipyridine and R.dtc is amyl-, isopentyl- or tertamyl-dtc (n-pentyl-, 3-metyl-butyl- and 2-methylbutan-dithiocarbamate, respectively) have been synthesized and characterized by elemental analysis, conductivity measurements and chemical analysis. The cytotoxic activities of synthesized complexes were investigated against human adenocarcinoma colorectal cell line (HT29) and human pancreatic cell line (Panc1), and compared with cisplatin and oxaliplatin, which display more anticancer activity for [Pt(bpy)(isopentyl.dtc)]NO3. The experimental fluorescence and circular dichroism results illustrated partially groove binding of [Pt(bpy)(amyl.dtc)]NO3 and [Pt(bpy)isopentyl.dtc)]NO3 on DNA, while [Pt(bpy)(tertamyl.dtc)]NO3 complex, can bind to DNA via intercalation. Finally, molecular docking simulation data of DNA interaction with three synthesized complexes showed [Pt(bpy)(amyl.dtc)]NO3 complex has the highest tendency and negative docking energy in structural change of DNA.Communicated by Ramaswamy H. Sarma.

Biological evaluations of newly-designed Pt(II) and Pd(II) complexes using spectroscopic and molecular docking approaches.

To perform biological evaluations of newly-designed Pt(II) and Pd(II) complexes, the present study was conducted with targeted protein human serum albumin (HSA) and HCT116 cell line as model of human colorectal carcinoma. The binding of Pt(II) and Pd(II) complexes to HSA was analyzed using fluorescence spectroscopy and molecular docking. The thermal stability and alterations in the secondary structure of HSA in the presence of Pt(II) and Pd(II) complexes were investigated using the thermal denaturation method and circular dichroism (CD) spectroscopy. The cytotoxicity of the Pt(II) and Pd(II) complexes was studied against the HCT116 cell line using MTT assay. The binding analysis revealed that the fluorescence findings were well in agreement with docking results such that there is only one binding site for each complex on HSA. Binding constants of 8.7 × 103 M-1, 2.65 × 103 M-1, 0.3 × 103 M-1, and 4.4 × 103 M-1 were determined for Pd(II) and Pt(II) complexes (I-IV) at temperature of 25 °C, respectively. Also, binding constants of 1.9 × 103 M-1, 15.17 × 103 M-1, 1.9 × 103 M-1, and 13.1 × 103 M-1 were determined for Pd(II) and Pt(II) complexes (I-IV) at temperature of 37 °C, respectively. The results of CD and thermal denaturation showed that the molecular structure of HSA affected by interaction with Pt(II) and Pd(II) complexes is stable. Cytotoxicity studies represented the growth suppression effect of the Pt(II) and Pd(II) complexes toward the human colorectal carcinoma cell line. Therefore, the results suggest that the new designed Pt(II) and Pd(II) complexes are well promising candidates for use in cancer treatment, particularly for human colorectal cancer. Communicated by Ramaswamy H. Sarma.

Biological effect and molecular docking of anticancer palladium and platinum complexes with morpholine dithiocarbamate on human serum albumin as a blood carrier protein.

The aim of this study was to examine the interaction of [Pd(2,2'-bipyridine) (morpholinedithiocarbamate)]NO3 and [Pt (2,2'-bipyridine)(morpholinedithiocarbamate)]NO3 with human serum albumin under physiological conditions by using fluorescence, absorption, and circular dichroism spectroscopic techniques. Spectroscopic analysis of the emission quenching at different temperatures demonstrated that the quenching mechanism was static quenching. From the circular dichroism results, thermal stability study, it was found that the interaction of the complexes with human serum albumin caused a conformational change of the protein reversibly. These 2 anticancer Pd and Pt complexes were activated against chronic myelogenous leukemia cell line K562, so that 50% cytotoxic concentration values of 16 and 26 µM for Pd and Pt complexes, respectively, were observed, which were much lower than that of cisplatin (154 µM). Biological activities of both Pd and Pt complexes were also assayed against selective microorganisms by the disc diffusion method. These results showed that the Pd(II) complex is antifungal agent but Pt(II) complex has antibacterial activity. Also, the interaction of both metal derivative complexes was studied by molecular docking. Complementary molecular docking results may be useful to determine the binding mechanism of human serum albumin in pharmaceutical and biophysical studies providing new insight in the novel pharmacology.