Synthesis and Physico-Chemical Characterizations of Novel Hydrazone Ligands and Their Metal Complexes against Hormone-Dependent and Independent Cancers

This work deals with the synthesis and physicochemical characterizations of a new group of novel retinoidal ligands and their metal complexes. Their in vitro anti-proliferative activities have shown that ligand L1 is effective against human breast cancer BT-20 and MCF-7 cell lines. At the same time, compound L2 exerts its effect on human prostate cancer PC-3 and human breast cancer MDA-MB-231 and MCF-7 cell lines respectively. The retinoid ligands exert their pleiotropic action toward retinoic acid receptors (RARs) than their metal complexes but all compounds exhibit concentration-dependent.

Enhanced effect of dimension of receptor-ligand complex and depletion effect on receptor-mediated endocytosis of nanoparticles

We present an extended analytical model including the depletion effect and the dimension of ligand-receptor complex, aiming to elucidate their influences on endocytosis of spherocylindrical nanoparticles （NPs）. It is found that the dimension of ligand-receptor complex （δ） and the depletion effect interrelatedly govern the optimal conditions of NP endocytosis. The endocytosis phase diagram constructed in the space of NP radius and relative aspect ratio indicates that the endocytosis of NP is enhanced evidently by reducing the optimal radius and the threshold radius of endocytosed NP. Meanwhile, through thermodynamic and kinetic analysis of the diffusion of receptors, the dependence of diffusion length on depletion effect and the dimension of ligand-receptor complex can be identified in great detail. For small aspect ratio, diffusion length decreases with increasing concentration c of small bioparticles in cellular environment. Endocytosis speed corresponding to large radius R and high concentration c of small bioparticles strongly depends on the increasing （2r-δ）. These results may show some highlights into the conscious design of NPs for diagnostic agents and therapeutic drug delivery applications.

Design of N-11-Azaartemisinins Potentially Active against Plasmodium falciparum by Combined Molecular Electrostatic Potential, Ligand-Receptor Interaction and Models Built with Supervised Machine Learning Methods

N-11-azaartemisinins potentially active against Plasmodium falciparum are designed by combining molecular electrostatic potential (MEP), ligand-receptor interaction, and models built with supervised machine learning methods (PCA, HCA, KNN, SIMCA, and SDA). The optimization of molecular structures was performed using the B3LYP/6-31G* approach. MEP maps and ligand-receptor interactions were used to investigate key structural features required for biological activities and likely interactions between N-11-azaartemisinins and heme, respectively. The supervised machine learning methods allowed the separation of the investigated compounds into two classes: cha and cla, with the properties εLUMO+1 (one level above lowest unoccupied molecular orbital energy), d(C6-C5) (distance between C6 and C5 atoms in ligands), and TSA (total surface area) responsible for the classification. The insights extracted from the investigation developed and the chemical intuition enabled the design of sixteen new N-11-azaartemisinins (prediction set), moreover, models built with supervised machine learning methods were applied to this prediction set. The result of this application showed twelve new promising N-11-azaartemisinins for synthesis and biological evaluation.

Role of osteoprotegerin/receptor activator of nuclear factor kappa B/receptor activator of nuclear factor kappa B ligand axis in nonalcoholic fatty liver disease

Concomitantly with the increase in the prevalences of overweight/obesity, nonalcoholic fatty liver disease(NAFLD) has worldwide become the main cause of chronic liver disease in both adults and children. Patients with fatty liver display features of metabolic syndrome(Met S), like insulin resistance(IR), glucose intolerance, hypertension and dyslipidemia. Recently, epidemiological studies have linked obesity, Met S, and NAFLD to decreased bone mineral density and osteoporosis, highlighting an intricate interplay among bone, adipose tissue, and liver. Osteoprotegerin(OPG), an important symbol of the receptor activator of nuclear factor-B ligand/receptor activator of nuclear factor kappa B/OPG system activation, typically considered for its role in bone metabolism, may also play critical roles in the initiation and perpetuation of obesityrelated comorbidities. Clinical data have indicated that OPG concentrations are associated with hypertension, left ventricular hypertrophy, vascular calcification, endothelial dysfunction, and severity of liver damage in chronic hepatitis C. Nonetheless, the relationship between circulating OPG and IR as a key feature of Met S as well as between OPG and NAFLD remains uncertain. Thus, the aims of the present review are to provide the existent knowledge on these associations and to discuss briefly the underlying mechanisms linking OPG and NAFLD.

Synthesis and Characterization of Chiral Organogallium and Indium Complexes with Salen Ligands

Several new chiral organogallium and indium complexes with chiral Salen (1 and 2) as anxciliary ligands have been synthesized and characterized by elemental analysis, IR, 1H NMR and Mass spectroscopy. For the gallium, mono and bimetallic complexes were obtained, whereas ring closure complexes of indium were obtained.

Increased Expression of Receptor Activator of Nuclear Factor-κB Ligand in Osteoblasts from Adolescent Idiopathic Scoliosis Patients with Low Bone Mineral Density

Persistent generalized low bone mineral density (BMD) has been reported in patients with adolescent idiopathic scoliosis (AIS).However,the exact mechanisms and causes of the low BMD in AIS patients are largely unknown.The purpose of this study was to examine the relationship between the receptor activator of NF-κB ligand (RANKL)/osteoprotegerin (OPG) levels in osteoblasts (OBs) from AIS patients with low BMD and with comparison made between the patients and controls.Twenty AIS patients and eight age-matched controls were included in the present study.The BMD of lumbar spine and proximal femur was measured in all subjects.OBs from the cancellous bone of each subject was harvested and primarily cultured.The mRNA and protein expression of RANKL and OPG in OBs was detected by RT-PCR and Western blotting.The results showed BMD was lower in AIS patients than in controls.A significantly higher mRNA and protein expression of RANKL was observed in OBs from AIS patients,while no significant difference was found in the expression of OPG between AIS patients and controls.As a result,RANKL/OPG ratio in patients with AIS was remarkably higher than controls.Our study preliminarily demonstrated expression of RANKL was higher in OBs from AIS patients with low BMD as compared with controls,suggesting the unbalanced RANKL/OPG ratio caused by an over-expression of RANKL in OBs may be responsible for the low BMD in AIS patients.

Intercalation Assembly, Characterization and Luminescent Properties of Novel Supramolecular Composite Materials, Tb(Ⅲ) Complex with Tetrapodal Ligand-Montmorillonite

Two kinds of Tb（ Ⅲ ） complexes with tetrapodal ligand, [TbL（NO3）]^3＋ and [TbL]^3＋ （L： 1,1, 1＇, 1＇-tera （ 2-pyridinecarboxylester ）-di （ trimethylpropane）） were intercalated into the interlayer space of montmorillonite （MT） by ion exchange and coordination reaction of L with the Tb^3＋ ion existing in the interlayer space of Tb-MT respectively. The obtained luminescent supramolecular composite materials, [ TbL （NO3） ]^2＋-MT and [TbL]^3＋-MT were characterized by elemental analysis, XRD, FT-IR, UV-vis and thermal analysis. At the same time, the luminescent properties of the materials were also studied. The results show that the intercalated materials with regular layered structure, good thermal stability and the interlayer spacing （d001） approximates to the size of the complex ions which are located in the interlayer space of MT in the form of a monolayer.

Synthesis of Eu(Ⅲ) and Tb(Ⅲ) Complexes with New Aryl Amide Type Tetrapodal Ligand and Their Luminescence Properties

A new aryl amide type tetrapodal ligand L (1, 1, 1, 1 tetrakis-{[(2 benzylaminoformyl) phenoxyl]methyl}methane) and its europium and terbium nitrate complexes were synthesized. The luminescence properties of these complexes were also studied.

Mechanism of cleaving DNA through hydrolysis of a novel complex of Mg containing dien ligand

A series of metal complexes were designed and synthesized and a novel binuclear magnesium complex has been selected, namely [Mg-2(dien)Cl(OH2)(2)]Cl-2 . H2O (dien=diethylene-triamine), which can cleave the plasmid pBR322 DNA effectively in close to physiological condition without adding any external materials. Through biological and chemical methods, especially the comparative experiments, we find the interaction between the complex and DNA belongs to hydrolytic mechanism.

Neuroprotective effects of receptor imidazoline 2 and its endogenous ligand agmatine

Receptor imidazoline 2 (I2) is one of the imidazoline receptors with high affinity for 3H-idazoxan. Receptor I2,being classified into I2A and I2B subtypes,is mainly localized to the outer membrane of mitochondria in liver,kidney and brain. Receptor I2,displaying high similarity of sequence with monoamine oxidase-B (MAO-B),is structurally related to MAO-B,but the I2 imidazoline binding site (I2BS) with ligand is distinct from the catalytic site of MAO-B. Agmatine is the endogenous ligand of receptor I2. Accumulating evidence have revealed that the activation of receptors I2 may produce neuroprotective effects by increasing expression of glial fibrillary acidic protein (GFAP) in astrocytes,inhibiting activity of MAO,reducing calcium overload in cells. Agmatine exerts neuroprotection against ischemia-hypoxia,injury,glutamate-induced neurotoxicity by activating imidazoline receptors,blocking N-methyl-D-aspartate (NMDA) receptor,inhibiting all isoforms of nitric oxide synthase (NOS),and selectively blocking the voltage-gated calcium channels (VGCC). It would be expected that agmatine is one of the potential neuroprotective agents.

Two Zinc Complexes Supported by in situ Formed Etheric Ligands

Two zinc complexes, [Zn(MPIP)Cl2](1) and [Zn(EPIP)Cl2](2), where MPIP = 1-(methoxymethyl)-3-(pyridin-2-yl)imidazo[1,5-a]pyridine and EPIP = 1-(ethoxymethyl)-3-(pyridin-2-yl)imidazo[1,5-a]pyridine, were synthesized under solvothermal conditions. The etheric ligand MPIP was formed in situ via metal ligand reaction between(3-(pyridin-2-yl)imidazo[1,5-a]pyridin-1-yl)methanol(HPIPM) and methanol solvent. Similarly, the ligand EPIP was generated in situ from the reaction of HPIPM with ethanol solvent. The structures of 1 and 2 were characterized by X-ray single-crystal diffraction analysis. They are four-coordinated mononuclear complexes, and the ZnII ion of 1 and 2 displays distorted tetrahedral geometry. The photoluminescent properties of 1 and 2 were investigated. Strong emissions were observed for both 1 and 2, which were ascribed as the intraligand(π-π*) fluorescent transitions. This paper provides a simple and efficient method for the synthesis of etheric compounds.

Expression of N-methyl-D-aspartic acid 2A-B and 2B receptors in anterior thalamic nucleus and subiculum complex of rats

BACKGROUND：Glutamate acid ionotropic receptor N-methyl-D-aspartic acid （NMDA） takes part in long-term potentiation, thereby influencing the process of learning and memory. OBJECTIVE： To verify expression of NMDA 2A/B and 2B receptors in the anterior thalamic nucleus and subiculum complex of rats. DESIGN, TIME AND SETTING： A single-sample observation was performed at Department of Anatomy in Dalian Medical University （Dalian, Liaoning, China） from April to September in 2007. MATERIALS： Ten adult Wistar rats were used for this study, as well as rabbit anti-NMDA 2A/B and 2B antibodies. METHODS： The rats were anesthetized and perfused, followed by brain resection and coronal sectioning of the brain tissue. A 1：3 series was selected for immunohistochemistry, using antibodies specific to NMDA 2A/B and 2B receptors. Photos were taken using the Nikon image analysis system. MAIN OUTCOME MEASURES： Expression and distribution of immunohistochemistry staining of NMDA 2A/B and 2B receptor subunits. RESULTS： There were a large number of NMDA 2A/B and 2B receptor-positive neurons distributed throughout the anterior dorsal thalamic nucleus. In the anterior ventral thalamic nucleus, distribution of positive neurons was rare, staining intensity was lighter, and cell bodies were smaller compared with the anterior dorsal thalamic nucleus. In the subiculum complex, staining intensity of NMDA 2A/B and 2B-positive neurons was weakest in the molecular layer and stronger in the pyramidal layer, in particular the region with large cell bodies adjacent to the molecular layer. In the multiform layer, more positive neurons of various sizes were detected. CONCLUSION： NMDA 2A/B and 2B receptor subunits were richly distributed in the anterior thalamic nucleus, with a small difference existing between the anterior dorsal nucleus and anterior ventral nucleus. These neurons were also differentially distributed within the three layers of the subiculum complex.

Synthesis and thermal studies of mixed ligand complexes of Cu(II), Co(II), Ni(II) and Cd(II) with mercaptotriazoles and dehydroacetic acid

A series of new mixed ligand complexes of cobalt(II), nickel(II), copper(II) and cadmium(II) have been synthesized with 3benzyl1H4[(2 methoxybenzylidine) amino]1, 2, 4triazole5 thione (MBT), 3bezyl1H4[(4chlorobenzylidine) amino]1, 2, 4triazole5thione (CBT), 3benzyl 1H4[(4nitrobenzylidine)amino]1, 2, 4triazole 5thione (NBT) and dehydroacetic acid sodium salt (Nadha). The mixed ligand complexes have been characterized by elemental analysis, spec troscopic spectral measurements (IR, UVVis.), molar conductance, magnetic measurements and thermal studies. The stoichiometry of these com plexes is M:L1:L2 = 1:1:1, 1:2:1 or 1:1:2 where L1 = NBT, CBT and MBT and L2 = Nadha. Tetrahedral structure was proposed for all Cd(II) mixed ligand complexes while the square planar geometry was proposed for Cu(II) mixed ligand complex with NBT. Octahedral structure was proposed for Ni(II), Co(II) mixed ligand complexes and Cu(II) mixed ligand complexes with CBT and MBT ligands. The thermal decomposition study of the prepared complexes was monitored by TG, DTG and DTA analysis in dynamic nitrogen atmosphere. TG, DTG and DTA studies confirmed the chemical formulations of theses complexes. The kinetic parameters were determined from the the thermal decomposition data using the graphical methods of CoatsRedfern and HorwitzMetzger. Thermodynamic parameters were calculated using standard relations.

Syntheses and Crystal Structures of Mono-and Binuclear Copper(Ⅱ) Mixed-ligand Complexes Involving Schiff Base

The mononuclear copper（Ⅱ） complex [Cu（L）（2-AP）] 1 and binuclear copper（Ⅱ） complex [Cu（L）（py）]2 2 （L = C10H11O5NS, taurine o-vanillin, py = prydine, 2-AP = 2-aminopyridine） with mixed ligand have been synthesized and characterized by X-ray diffraction method. Crystal data for 1： orthorhombic, space group Pbca with a = 11.921（4）, b = 15.816（6）, c = 17.076（6） A, V= 3219.7（19） A^3, C15H17CuN3O5S, Z = 8, Mr = 414.92, De = 1.712 g/cm^3,μ（MoKα） = 1.520 mm^-1, F（000） = 1704, the final R = 0.0300 and wR = 0.0705 for 2840 observed reflections with I 〉 2σ（I）; and crystal data for 2： monoclinic, space group P21/c with a = 7.929（3）, b = 17.038（5）, c = 11.734（4） A, β = 98.162（6）°, V = 1569.1（9） A^3, C15H16CuN2O5S, Z = 4, Mr = 399.90, Dc = 1.693 g/cm^3, F（000） = 820,μ（MoKα） = 1.554 mm^-1, the final R = 0.0351 and wR = 0.0848 for 2767 observed reflections （I 〉 2σ（I））. The molecular structure of complex 1 consists of one tetra-coordinated Cu（Ⅱ） atom generating a slightly distorted square plane, and a one-dimensional chain structure is formed by intermolecular hydrogen bonds. Complex 2 consists of a diphenolic hydroxyl O-bridged binuclear copper（Ⅱ） structure. The crystal structures of complexes 1 and 2 reveal that the coordinate copper centers are bound to both nitrogen and oxygen atom donors. The usual N,O-trans arrangement of ligands is observed in both cases.

Effect of Triptolide on Expression of Receptor Activator of Nuclear Factor-κB Ligand in Rat Adjuvant Induced Arthritis

The effect of triptolide （TP） on the expression of receptor activator of nuclear factor-κB ligand （RANKL） and osteoprotegerin （OPG） was explored in rat adjuvant induced arthritis （AA）. AA was induced in Wistar rats. Arthritis rats were treated with TP and methotrexate （MTX） at the onset （day 9） of arthritis. On the peak of arthritis （day 24）, the expression of RANKL and OPG protein in the joints and RANKL mRNA in peripheral blood mononuclear cells （PBMC） was detected. TNF-α and IL-1β levels in peripheral blood were determined. Bone erosion scores were also evaluated. The results showed that bone erosion scores in TP and MTX groups were lower than in AA group （.P〈0.01） ; The expression levels of RANKL in the synovium （P〈0.01） and bone （P〈0.05）, and OPG level in synovium （P〈0.05） were lower in TP group than in AA group （P〈0.05）. In TP group, the expression levels of RANKL mRNA and TNF-α, IL-1β in PBMC were lower than in AA group （all P〈0.01）. It was concluded that TP could inhibit rat adjuvant arthritis bone erosion by suppressing the expression of RANKL.

Synthesis and Thermal Decomposition Kinetics of La(Ⅲ) Complex with Unsymmetrical Schiff Base Zwitterion Ligand

A new unsymmetrical solid Schiff base (LLi) was synthesized using L-lysine, o-vanillin and 2-hydroxy-l-naphthaldehyde. Solid La(Ⅲ) complex of this ligand [LaL(NO3)](NO3)·2H2O was prepared and characterized by elemental analyses, IR, UV and molar conductance. The thermal decomposition kinetics of the complex for the second stage were studied under non-isothermal condition by TG and DTG methods. The kinetic equation may be expressed as: dα/dt=A·e-E/RT·(1-α)2. The kinetic parameters(E, A), activation entropy S≠ and activation free-energy G≠ were also gained.

Syntheses and Crystal Structures of Silver(I) Complexes by Depolymerizing [Ag(C≡CPh)]_n with a NP_3 Ligand

Two silver(I) complexes were prepared by the reaction of [Ag(C≡CPh)]n with NP3 [NP3 = N(CH2CH2PPh2)3] or with NP3 and [Cu(CH3CN)4]ClO4. Complex 1 [(Ag2Cl(NP3)2)(Ag5- (C≡CPh)6)] contains both NP3 and PhC≡C- ligands. The complex cation is (Ag2Cl(NP3)2)+, in which two Ag(NP3)+ cations were bridged by a Cl- donor. The anion is (Ag5(C≡CPh)6)-, where five Ag+ ions are linked by six C≡CPh- to form a pentanuclear cluster. Complex 2 only contains NP3 ligand, where the silver center adopts a trigonal-bipyramidal geometry. Crystal data for 1: C133H116Ag7Cl3- N2P6, Mr = 2789.54, triclinic, space group P1, a = 13.0780(2), b = 15.3678(2), c = 31.2041(3) ?, α = 91.3928(7), β = 90.9328(8), γ = 96.0244(4)o, V = 6233.8(1) ?3, T = 293(2) K, Z = 2, Dc = 1.486 g/cm3, F(000) = 2796, μ = 1.266 mm-1, the final R = 0.0746 and wR = 0.1953 for 16475 observed reflections with I > 2σ(I). Crystal data for 2: C42H42AgClNO4P3, Mr = 861.00, trigonal, space group R3, a = 17.451(1), b = 17.451(1), c = 11.3985(7) ?, V = 3006.0(3) ?3, T = 293(2) K, Z = 3, Dc = 1.427 g/cm3, F(000) = 1326, μ = 0.731 mm-1, the final R = 0.0251 and wR = 0.0663 for 1499 observed reflections with I > 2σ(I).

Synthesis, Characterization and Antibacterial Activity of New Ln(Ⅲ) Complex with Unsymmetrical Schiff Base Ligand

A new unsymmetrical Schiff base ligand (H_2LLi) was synthesized using L-lysine, o-vanillin and salicylaladyde. Three solid metal complexes of this ligand [Ln(H_2L)(NO_3)] NO_3·2H_2O (Ln=Sm, Ho, Tm) were prepared and characterized by elemental analyses, IR spectra, UV spectra, TG-DTG and molar conductance. The ligand synthesized are chelating agent. The nitrogen atoms of Schiff base, oxygen atoms of hydroxybenzene, methoxide and carboxyl are all coordinated to the metal ions. Carboxyl and the nitrate ion within the coordination sphere are coordinated to the metal ion in a mondentate or bidentate fashion. Water molecules are lied in crystal substances. The antibacterial activity of the ligand and its complexes was also studied. The antibacterial experiments indicate that they have antibacterial activity to E. coli, S. aureus, B. subtilis and the complexes have higher activity than the ligand.

Expression of CC Chemokine Ligand 20 and CC Chemokine Receptor 6 mRNA in Patients with Psoriasis Vulgaris

Summary: In order to explore the possible role of CC chemokine ligand 20 (CCL20) and its receptor CC chemokine receptor 6 (CCR6) in the pathogenesis of psoriasis, the expression levels of mRNA of them in psoriatic lesions were investigated. The skin biopsies were collected from skin lesions in 35 cases of psoriasis vulgaris and 18 normal controls. RT-PCR was used to semi-quantitatively analyze the mRNA expression of CCL20 and CCR6 in the psoriatic lesions and the normal skin tissues. The results showed that the mRNA of CCL20 and CCR6 was present in every specimen. The expression levels of CCL20 mRNA in skin lesions were 1.1397±0.0521, which were greatly higher than those in normal controls (0.8681±0.0308) (P<0.001). The expression levels of CCR6 mRNA in skin lesions were 1.1103±0.0538, significantly higher than in the controls (0.9131±0.0433, P<0.001). These findings indicate that up-regulated expression of CCL20 and CCR6 mRNA might be related to the pathogenesis of psoriasis.