Synthesis, molecular docking and evaluation of thiazolyl-pyrazoline derivatives containing benzodioxole as potential anticancer agents.

A series of novel thiazolyl-pyrazoline derivatives containing benzodioxole (C1-C20) have been designed and synthesized. Among of the synthesized compounds, 2-(5-(benzo[d][1,3]dioxol-5-yl)-3-(4-bromophenyl)-4,5-dihydro-1H-pyrazol-1-yl)-4-(4-bromophenyl)thiazole (C6) displayed the most potent inhibitory activity for HER-2 (IC(50) = 0.18 µM for HER-2). Antiproliferative assay results indicated that compound C6 owned high antiproliferative activity against MCF-7 and B16-F10 in vitro, with IC(50) value of 0.09 and 0.12 µM, respectively, being comparable with the positive control Erlotinib. Docking simulation was further performed to determine the probable binding model. Based on the preliminary results, compound C6 with potent inhibitory activity in tumor growth would be a potential anticancer agent.

Syntheses, Characterization, Crystal Structures and Antimicrobial Activity of Copper(II), Nickel(II) and Zinc(II) Complexes Derived from 5-Bromo-2-((cychlopentylimino)methyl)phenol.

Four new complexes of copper(II), nickel(II) and zinc(II), [CuL2] (1), [Ni3L2(4-BrSal)2(CH3COO)2(CH3OH)2]·2CH3OH (2), [ZnBr2(HL)2] (3) and [ZnL(dca)]n (4), where L is 5-bromo-2-((cychlopentylimino)methyl)phenolate, HL is the zwitterionic form of 5-bromo-2-((cychlopentylimino)methyl)phenol, 4-BrSal is the monoanionic form of 4-bromosalicylaldehyde, dca is dicyanamide anion, were synthesized and characterized by elemental analysis, IR and UV-Vis spectroscopy. The structures of the complexes were further confirmed by single crystal X-ray structure determination. Complex 1 is a mononuclear copper(II) compound, with a crystallographic two-fold rotation axis symmetry. The Cu atom is in distorted square planar coordination. Complex 2 is a trinuclear nickel(II) compound, with an inversion center symmetry. The Ni atoms are in octahedral coordination. Complex 3 is a mononuclear zinc(II) compound, while complex 4 is a dca bridged polymeric zinc(II) compound. The Zn atoms are in tetrahedral coordination. The compounds were assayed for their antimicrobial activities.

Syntheses, Structures and Insulin-Like Activity of Two Oxidovanadium(V) Complexes with Similar Nicotinohydrazone Ligands.

Two new oxidovanadium(V) complexes, [VOL1(HQ)] (1) and [VOL2(SAH)] (2), were prepared by the reaction of [VO(acac)2] (where acac = acetylacetonate) with N'-(3-ethoxy-2-hydroxybenzylidene)nicotinohydrazide (H2L1) and 8-hydroxyquinoline (HHQ), and N'-(2-hydroxy-4-methoxybenzylidene)nicotinohydrazide (H2L2) and salicylhydroxamic acid (HSAH), respectively, in methanol. Crystal and molecular structures of the complexes were determined by elemental analysis, infrared spectroscopy and single crystal X-ray diffraction. The V atoms in both complexes are in octahedral coordination. Thermal stability of the complexes was studied. Both complexes can decrease the blood glucose level in alloxan-diabetic mice, but the blood glucose level in the treated normal mice was not altered.

Syntheses, Characterization, Crystal Structures and Antimicrobial Activity of Schiff Base Copper(II) Complexes Derived from 2-Bromo-6-((2-(isopropylamino)ethylimino)methyl)phenol.

Three new copper(II) complexes, [Cu(LH)2]Br2 (1), [Cu(LH)2]NCS2 (2), and [Cu(LH)2](NO3)2 (3), where LH is the zwitterionic form of 2-bromo-6-((2-(isopropylamino)ethylimino)methyl)phenol (HL), were synthesized and characterized by elemental analysis, IR and UV-vis spectroscopy. The structures of the complexes were further confirmed by single crystal X-ray structure determination. All compounds are mononuclear copper(II) complexes. The Cu atoms in the complexes are coordinated by two imino N and two phenolate O atoms from two LH ligands, forming square planar coordination. The compounds were assayed for their antimicrobial activities.

Syntheses, Crystal Structures and Antimicrobial Property of Schiff Base Copper(II) Complexes.

Four new copper(II) complexes, [CuL1(?1,1-N3)]n (1), [CuL1(?1,3-NCS)]n (2), [Cu(HL2)2](SCN)2 (3) and [Cu(L2)2] (4), where L1 and L2 are 2-((2-(dimethylamino)ethylimino)methyl-4,6-difluorophenolate and 2,4-difluoro-6-((3-morpholinopropylimino) methyl)phenolate, respectively, and HL2 is 2-((2-(dimethylammonio)ethylimino)methyl-4,6-difluorophenolate, were synthesized and characterized by elemental analysis, IR and UV-vis spectroscopy. The structures for the complexes were further confirmed by single crystal X-ray structure determination. Complexes 1 and 2 are polymeric copper(II) complexes, with the Cu atoms in square pyramidal coordination. Complexes 3 and 4 are mononuclear copper(II) complexes, with the Cu atoms in square planar coordination. The complexes were assayed for their antimicrobial properties.

Single Heterocyclic Compounds as Monoamine Oxidase Inhibitors: From Past to Present.

Inhibitors of monoamine oxidase (MAO) have shown therapeutic values in a variety of neurodegenerative diseases such as depression, Parkinson's disease and Alzheimer's disease. Heterocyclic compounds exhibit a broad spectrum of biological activities and vital leading compounds for the development of chemical drugs. Herein, we focus on the synthesis and screening of novel single heterocyclic derivatives with MAO inhibitory activities during the past decade. This review covers recent pharmacological advancements of single heterocyclic moiety along with structure- activity relationship to provide better correlation among different structures and their receptor interactions.

Phenothiazine-based fluorescence probe for ratiometric imaging of hydrazine in living cells with remarkable Stokes shift.

By modifying the 10-butyl-2-methoxy-10H-phenothiazine-3-carbaldehyde with malonontrile group, a new fluorescent sensor PBM for selective detection of hydrazine in ratiometric mode has been developed. Probe PBM owned the advantages of quick response (10 min), remarkable Stokes shift (168 nm for PBM, 161 nm for PBM-NH2), excellent selectivity, high sensitivity (detection limit of 63.2 nM was obtained from in vitro experiment), profound ratiometric change (82-fold) and low cytotoxicity in response to hydrazine. Additionally, it could be utilized to monitor hydrazine in gas state with various concentrations through vivid color changes and imaged hydrazine in living MCF-7 cells with excellent performance.

Two Vanadium(V) Complexes Derived from Bromo and Chloro-Substituted Hydrazone Ligands: Syntheses, Crystal Structures and Antimicrobial Property.

Two vanadium(V) complexes derived from the bromo and chloro-substituted hydrazones N'-(4-bromo-2-hydroxybenzylidene)- 2-chlorobenzohydrazide (H2L1) and N'-(3-bromo-5-chloro-2-hydroxybenzylidene)-3-methylbenzohydrazide (H2L2) with the formula [VOL1(OCH3)(CH3OH)] (1) and [VOL2(OCH3)(CH3OH)] (2) were newly synthesized and characterized by IR, UV-Vis and 1H NMR spectroscopy. The structures of H2L1 and the complexes were further confirmed by single crystal X-ray diffraction. Both vanadium complexes are mononuclear, with the metal atoms coordinated by the hydrazone ligands, methanol ligands, and methanolate ligands, and the oxo groups, forming octahedral geometry. The hydrazones and the vanadium complexes were assayed for the antimicrobial activities on Bacillus subtilis, Staphylococcus aureus, Escherichia coli, and Pseudomonas fluorescence, and the fungi Candida albicans and Aspergillus niger. The existence of the bromo and chloro groups in the hydrazone ligands may improve the antimicrobial property.

N'-(5-Chloro-2-hydroxy-benzyl-idene)-4-hydroxy-benzohydrazide.

The title Schiff base compound, C(14)H(11)ClN(2)O(3), was prepared by the reaction of 5-chloro-salicylaldehyde and 4-hydroxy-benzohydrazide. The mol-ecule exists in a trans configuration with respect to the methyl-idene group. The dihedral angle between the two benzene rings is 40.1 (2)°. An intra-molecular O-H⋯N hydrogen bond helps to stabilize the mol-ecular conformation. In the crystal structure, mol-ecules are linked into a three-dimensional network by inter-molecular N-H⋯O and O-H⋯O hydrogen bonds.

Synthesis, Crystal Structure and Antimicrobial Activity of a Linear Trinuclear Nickel(II) Complex with Schiff Base Ligand.

A new linear trinuclear Schiff base nickel(II) complex, [NiNiL(α2-α1:α1-OAc)(OH2)2]·H2O, where L is the dianionic form of N,N'-bis(5-chloro-2-hydroxybenzylidene)-1,3-propanediamine (H2L), was synthesized and characterized by elemental analyses, IR spectroscopy, and X-ray single-crystal determination. There are three bridges across the Ni-Ni atom pairs, involving two phenolate O atoms of a Schiff base ligand, and an O-C-O moiety of a α2-α1:α1-OAc group. The Ni atoms have octahedral coordination. The acetate bridges linking the central and terminal nickel atoms are mutually trans. The adjacent NiαααNi distances are 3.047(1) α. The complex was evaluated for its antibacterial (Bacillus subtilis, Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa) and antifungal (Candida albicans and Aspergillus niger) activities by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) method.

Synthesis, Characterization and Crystal Structures of Cobalt(II), Zinc(II) and Cadmium(II) Complexes Derived from 2-Hydroxy-N'-(pyridin-2-ylmethylene)benzohydrazide with Antimicrobial Activity.

Three new cobalt(II), zinc(II) and cadmium(II) complexes, [CoL2]·2CH3OH·H2O (1), [ZnL2] (2) and [Cd(HL)2(NO3)]N3 (3), were prepared from 2-hydroxy-N'-(pyridin-2-ylmethylene)benzohydrazide (HL). The complexes have been characterized by IR, UV-Vis and single-crystal X-ray diffraction techniques. X-ray analysis indicates that the complexes are mononuclear species, with the metal atoms in octahedral coordination. The hydrazone compound and its complexes were evaluated for their antibacterial (Bacillus subtilis, Staphylococcus aureus, Escherichia coli, and Pseudomonas fluorescence) and antifungal (Candida albicans and Aspergillus niger) activities. The complexes have effective activities against the bacteria.

Vanadium(V) Complexes with Bromo-Substituted Hydrazones: Synthesis, Characterization, X-ray Crystal Structures and Antimicrobial Activity.

Two new VV complexes with the bromo-substituted hydrazones N'-(3-bromo-2-hydroxybenzylidene)-3-hydroxy-4-methoxybenzohydrazide (H2L1), N'-(3-bromo-2-hydroxybenzylidene)-3,5-dimethoxybenzohydrazide (H2L2), [VOL1(OCH3)(CH3OH)] (1) and [VOL2(OCH3)(CH3OH)] (2), were synthesized and structurally characterized by IR, UV-Vis and 1H NMR spectroscopy, as well as single-crystal X-ray determination. The V atom in the mononuclear complexes are six-coordinated in octahedral geometry. The free hydrazones and the complexes were studied on their antibacterial activity on S. aureus, B. subtilis, E. coli and P. fluorescence, and antifungal activity on C. albicans and A. niger. The bromo groups of the hydrazone ligands may increase their antibacterial activity.

2-Hydr-oxy-N'-(2-methoxy-naphthyl-idene)benzohydrazide.

The title Schiff base compound, C(19)H(16)N(2)O(3), prepared by the reaction of 2-meth-oxy-1-naphthyl-aldehyde and 2-hydroxy-benzohydrazide, crystallizes with two independent mol-ecules in the asymmetric unit. Each mol-ecule exists in a trans configuration with respect to the methyl-idene group. The naphthyl ring system make dihedral angles of 65.0 (2)° and 55.8 (2)° with the planes of the benzene rings. Intra-molecular N-H⋯O and O-H⋯O hydrogen bonds help to stabilize the mol-ecular conformations. In the crystal structure, mol-ecules are linked into one-dimensional chains parallel to the c axis by inter-molecular O-H⋯N and O-H⋯O hydrogen bonds.

4-Meth-oxy-N'-(2-methoxy-naphthyl-idene)benzohydrazide.

The mol-ecule of the title Schiff base compound, C(20)H(18)N(2)O(3), prepared by the reaction of 2-meth-oxy-1-naphthyl-aldehyde and 4-methoxy-benzohydrazide, exists in a trans configuration with respect to the imine group. The naphthyl ring system makes a dihedral angle of 71.4 (2)° with the mean plane of the benzene ring. In the crystal structure, mol-ecules are linked into one-dimensional chains parallel to the c axis by inter-molecular N-H⋯O hydrogen bonds.

Effect of superoxide dismutase and malondialdehyde metabolic changes on carcinogenesis of gastric carcinoma.

AIM: To investigate the relationship between the superoxide dismutase (SOD), malondialdehyde (MDA) metabolic changes and the gastric carcinogenesis. METHODS: The SOD activity and MDA content were measured in the gastric tissues from the focus center, peripheral and far-end areas of gastric carcinoma (n = 52) and gastric ulcer (n = 10). All the tissues were subjected to routine histological examinations and classifications. RESULTS: The SOD activity was greatly reduced but the MDA content was markedly increased in the center areas of the non-mucous gastric carcinoma (non-MGC); and the poorly differentiated gastric carcinoma varied. The SOD activity was gradually decreased and the MDA content was gradually increased in the tissues from the focus far-end, peripheral to center areas of non-MGC. Both of the SOD activity and the MDA content were significantly declined and were respectively at same low level in the tissues from the focus center, peripheral, and far-end area with the mucous gastric carcinoma (MGC). In contrast to the gastric ulcer and grade I or II of non-MGC, the same level of the SOD activity and the MDA content were found in the focus center areas. Between non-MGC (groups A-D) and gastric ulcer (group F), the differences of SOD activity and MDA content were very noticeable in the gastric tissues from the focus peripheral and far-end areas, in which the SOD activity showed noticeable increase and the MDA content showed noticeable decrease in the gastric ulcer. CONCLUSION: The active free radical reaction in the gastric tissues can induce the carcinogenesis of non-MGC. The utmost low ability of antioxidation in the gastric tissues can induce the carcinogenesis of MGC. The metabolic change of the free radicals centralized mostly in the center of ulcerated lesions only, which suggested the ability of antioxidation was declined only in these lesions. However, the metabolism of free radicals varied significantly and the ability of antioxidation declined not only in the local focus area but also in the abroad gastric tissues with gastric carcinoma.

Network Analyses of Gene Expression following Fascin Knockdown in Esophageal Squamous Cell Carcinoma Cells.

Fascin-1 (FSCN1) is an actin-bundling protein that induces cell membrane protrusions, increases cell motility, and is overexpressed in various human epithelial cancers, including esophageal squamous cell carcinoma (ESCC). We analyzed various protein-protein interactions (PPI) of differentially-expressed genes (DEGs), in fascin knockdown ESCC cells, to explore the role of fascin overexpression. The node-degree distributions indicated these PPI sub-networks to be characterized as scale-free. Subcellular localization analysis revealed DEGs to interact with other proteins directly or indirectly, distributed in multiple layers of extracellular membrane-cytoskeleton/ cytoplasm-nucleus. The functional annotation map revealed hundreds of significant gene ontology (GO) terms, especially those associated with cytoskeleton organization of FSCN1. The Random Walk with Restart algorithm was applied to identify the prioritizations of these DEGs when considering their relationship with FSCN1. These analyses based on PPI network have greatly expanded our comprehension of the mRNA expression profile following fascin knockdown to future examine the roles and mechanisms of fascin action.

A systematic analysis of human lipocalin family and its expression in esophageal carcinoma.

The lipocalin proteins (lipocalins) are a large family of small proteins characterized by low sequence similarity and highly conserved crystal structures. Lipocalins have been found to play important roles in many human diseases. For this reason, a systemic analysis of the molecular properties of human lipocalins is essential. In this study, human lipocalins were found to contain four structurally conserved regions (SCRs) and could be divided into two subgroups. A human lipocalin protein-protein interaction network (PPIN) was constructed and integrated with their expression data in esophageal carcinoma. Many lipocalins showed obvious co-expression patterns in esophageal carcinoma. Their subcellular distributions also suggested these lipocalins may transfer signals from the extracellular space to the nucleus using the pathway-like paths. These analyses also expanded our knowledge about this human ancient protein family in the background of esophageal carcinoma.

Shortest path analyses in the protein-protein interaction network of NGAL (neutrophil gelatinase-associated lipocalin) overexpression in esophageal squamous cell carcinoma.

NGAL (neutrophil gelatinase-associated lipocalin) is a novel cancer-related protein involves multiple functions in many cancers and other diseases. We previously overexpressed NGAL to analyze its role in esophageal squamous cell carcinoma (ESCC). In this study, a protein-protein interaction (PPI) was constructed and the shortest paths from NGAL to transcription factors in the network were analyzed. We found 28 shortest paths from NGAL to RELA, most of them obeying the principle of extracellular to cytoplasm, then nucleus. These shortest paths were also prioritized according to their normalized intensity from the microarray by the order of interaction cascades. A systems approach was developed in this study by linking differentially expressed genes with publicly available PPI data, Gene Ontology and subcellular localizaton for the integrated analyses. These shortest paths from NGAL to DEG transcription factors or other transcription factors in the PPI network provide important clues for future experimental identification of new pathways.

Bis(micro-4-chlorobenzoato-kappa(2)O:O)bis[(2-aminopyridine-kappaN)silver(I)].

The title compound, [Ag(2)(C(7)H(4)ClO(2))(2)(C(5)H(6)N(2))(2)], lies about an inversion centre and the Ag atom is three-coordinated by two O atoms and one N atom from three different ligands. The 4-chlorobenzoate anion acts as a monodonor ligand, bridging two inversion-related Ag atoms of the compound into a dimer. There are weak intermolecular N-H.O hydrogen bonds in the structure.