Synthesis, Crystal Structures, Molecular Docking and MAO-B Inhibitory Activity of Transition Metal Complexes Derived from 2-(4-(Pyridin-2-yl)piperazin-1-yl)acetic Acid.

Three new complexes derived from 2-(4-(pyridin-2-yl)piperazin-1-yl)acetic acid (HL), [M(L)2(H2O)2] where M = CuII (1), ZnII (2) and CdII (3), have been synthesized and characterized by IR spectroscopy, elemental analysis and X-ray crystallography. The inhibitory activity of these three complexes against MAO-B was tested in vitro, and the molecular docking experiments were also carried out to rationalize their binding models. Both the experimental and docking simulation results indicated that complex 1 has the best inhibitory activity with IC50 value being 6.5 ± 0.31 µM.

Synthesis, crystal structures, molecular docking, and in vitro biological activities of transition metals with 4-(2,3-dichlorophenyl)piperazine-1-carboxylic acid.

Four novel mononuclear complexes, [Cd(L)2·2H2O] (1), [Ni(L)2·2H2O] (2) [Cu(L)2·H2O] (3), and [Zn(L)2·2H2O] (4) (CCDC numbers: 1444630-1444633 for complexes 1-4) (HL=4-(2,3-dichlorophenyl)piperazine-1-carboxylic acid) were synthesized, and have been characterized by IR spectroscopy, elemental analysis, and X-ray crystallography. Molecular docking study preliminarily revealed that complex 1 had potential telomerase inhibitory activity. In accordance with the result of calculation, in vitro tests of the inhibitory activities of complex 1 against telomerase showed complex 1 (IC50=8.17±0.91µM) had better inhibitory activities, while complexes 2, 3 and 4 showed no inhibitory activities. Antiproliferative activity in human cancer cell line HepG2 was further determined by MTT assays. The IC50 value (6.5±0.2µM) for the complex 1 having good inhibitory activity against HepG2 was at the same micromolar concentrations with cis-platinum (2.2±1.2µM). While the IC50 value for the metal-free ligand, complex 2, 3 and 4 was more than 100µM. These results indicated that telomerase was potentially an anticancer drug target and showed that complex 1 was a potent inhibitor of human telomerase as well as an antiproliferative compound.

Synthesis, Structural Diversity and Mimic Superoxide Dismutase of Mn(II) Complexes Derived from N, O-donor Schiff bases.

Two new potentially tetradentate Schiff base ligands N'-(pyridin-2-ylmethylene)nicotinohydrazide (L1), and N'-(pyridin-2-ylmethylene)isonicotinohydrazide (L(2)) were synthesized. Reactions of hydrazone ligands L(1) and L(2) with Mn(NO(3))(2) afford two mononuclear Mn(II) complexes, [Mn(L(1))(NO(3))(H(2)O)(2)]•(NO(3)) (1) and [Mn(L(2))(2)(NO(3))(H(2)O)]•(NO(3)) (2). For complexes 1 and 2, L(1) and L(2) act as pincer-like tridentate or bidentate ligands, respectively. The Mn(II) ions in the two compounds are both in heptacoordinated environment, while the two molecules display diverse solid-state supramolecular structures because of the different orientation of Npyridine and hydrogen bonding patterns of nitrate anions. Complex 1 features 2D supramolecular sheet, while complex 2 is double-chain supramolecular structure. Both of the two complexes exhibit moderate superoxide dismutase (SOD) mimetic activity.

Synthesis, crystal structures, molecular docking, and urease inhibitory activity of transition metal complexes with 2-[4-(4-fluorophenyl)piperazin-1-yl]acetic acid.

Two novel mononuclear complexes, [Cu(L)(2)(H(2)O)]·(2)H(2)O (1) and [Ni(L)(2)(H(2)O)(2)] (2) (HL = 2-[4-(4-fluorophenyl)piperazin-1-yl]acetic acid) were synthesized and structurally determined by single-crystal X-ray diffraction. Their inhibitory activities were tested in vitro against jack bean urease. Molecular docking was investigated to determine the probable binding mode. The experimental values and docking simulation exhibited that complex 1 had better inhibitory activity than the positive reference aceto hydroxamic acid (AHA), showing IC(50) value of 0.15 ± 0.08 µM, while 2 showed no inhibitory activity.

Salvia miltiorrhiza: A source for anti-Alzheimer's disease drugs.

CONTEXT: Alzheimer's disease (AD) is a devastating neurodegenerative disorder that affects millions of elderly people worldwide. However, no efficient therapeutic method for AD has yet been developed. Recently, Salvia miltiorrhiza Bunge (Lamiaceae), a well-known traditional Chinese medicine which is widely used for treating cardio-cerebrovascular, exerts multiple neuroprotective effects and is attracting increased attention for the treatment of AD. OBJECTIVE: The objective of this study is to discuss the neuroprotective effects and neurogenesis-inducing activities of S. miltiorrhiza components. METHODS: A detailed search using major electronic search engines (such as Pubmed, ScienceDirect, and Google Scholar) was undertaken with the search terms: Salvia miltiorrhiza, the components of S. miltiorrhiza such as salvianolic acid B, salvianolic acid A, danshensu, tanshinone I, tanshinone IIA, cryptotanshinone, dihydrotanshinone, and neuroprotection. RESULTS: Salvia miltiorrhiza components exert multiple neuroprotective potentials relevant to AD, such as anti-amyloid-ß, antioxidant, anti-apoptosis, acetylcholinesterase inhibition, and anti-inflammation. Moreover, S. miltiorrhiza promotes neurogenesis of neural progenitor cells/stem cells in vitro and in vivo. CONCLUSIONS: The properties of S. miltiorrhiza indicate their therapeutic potential in AD via multiple mechanisms. In addition, S. miltiorrhiza provides lead compounds for developing new drugs against AD.

Discovery of phenylpiperazine derivatives as IGF-1R inhibitor with potent antiproliferative properties in vitro.

A series of phenylpiperazine derivatives (3a-3q) were designed and synthesized. In vitro assays indicated that several phenylpiperazine derivatives had excellent antiproliferative properties against four cancer cell lines including multidrug-resistant cancer cell lines, with IC50 values in the low micromolar range. The average IC50 of the most active compound 3b is 0.024µM to the MCF-7 cell line. In addition, the mechanism of action of these new analogues was investigated by molecular docking studies, insulin-like growth factor 1-receptor (IGF-1R) kinase assay and apoptosis induced assay. These studies confirmed that these new phenylpiperazine derivatives maintain their mechanisms of action by disrupting IGF-1R kinase.

Synthesis and antifungal activity of 1,2,3-triazole phenylhydrazone derivatives.

A series of 1,2,3-triazole phenylhydrazone derivatives were designed and synthesized as antifungal agents. Their structures were determined based on (1)H-NMR spectroscopy, MS, elemental analysis and X-ray single-crystal diffraction. The antifungal activities were evaluated against four phytopathogenic fungi including Rhizoctonia solani, Sclerotinia sclerotiorum, Fusarium graminearum and Phytophthora capsici, by the mycelium growth inhibition method in vitro. Compound 5p exhibited significant anti-phytopathogenic activity, with the EC50 values of 0.18, 2.28, 1.01, and 1.85 µg mL(-1), respectively. In vivo testing demonstrated that 5p was effective in the control of rice sheath blight, rape sclerotinia rot and fusarium head blight. A 3D-QSAR model was built for a systematic SAR profile to explore more potent 1,2,3-triazole phenylhydrazone analogs as novel fungicides.

Synthesis and Crystal Structures of Benzohydroxamate-Coordinated Vanadium(V) Oxo Complexes with Aroylhydrazone Ligands.

Reaction of [VO(acac)(2)] (where acac = acetylacetonate), benzohydroxamic acid (Hbha), and two similar aroylhydrazone ligands in methanol produced two benzohydroxamate-coordinated mononuclear vanadium(V) oxo complexes with general formula [VOL(bha)], where L = L(1) = N'-(5-bromo-2-hydroxybenzylidene)-2-fluorobenzohydrazide (H(2)L(1)), and L = L(2) = N'-(3-bromo-2-hydroxybenzylidene)-2-fluorobenzohydrazide (H(2)L(2)). Crystal and molecular structures of the complexes were determined by single crystal X-ray diffraction method. All of the investigated compounds were further characterized by elemental analysis, and FT-IR and UV-Vis spectra. Single crystal X-ray structural studies indicate that the benzohydrazone ligands coordinate to the VOcores through phenolate O, imino N, and enolate O atoms, and the benzohydroxamate ligands coordinate to the VO cores through deprotonated hydroxyl O and carbonyl O atoms. The V atoms in both complexes are in octahedral coordination. Thermal stability of the complexes was studied.

Synthesis and antitumor activity of 1,3,4-oxadiazole possessing 1,4-benzodioxan moiety as a novel class of potent methionine aminopeptidase type II inhibitors.

A series of 1,3,4-oxadiazole derivatives containing 1,4-benzodioxan moiety (7a-7q) have been designed, synthesized and evaluated for their antitumor activity. Most of the synthesized compounds were proved to have potent antitumor activity and low toxicity. Among them, compound 7a showed the most potent biological activity against Human Umbilical Vein Endothelial cells, which was comparable to the positive control. The results of apoptosis and flow cytometry (FCM) demonstrated that compound 7a induce cell apoptosis by the inhibition of MetAP2 pathway. Molecular docking was performed to position compound 7a into MetAP2 binding site in order to explore the potential target.

Binuclear and chain-structure zinc(II) complexes constructed from 3,4-dimethoxy-trans-cinnamic acid and N-donor coligands 4-(1H-pyrazol-3-yl)pyridine and 4,4'-bipyridine.

3,4-Dimethoxy-trans-cinnamic acid (Dmca) reacts with zinc sulfate in the presence of 4-(1H-pyrazol-3-yl)pyridine (L1) or 4,4'-bipyridine (L2) under hydrothermal conditions to afford two mixed-ligand coordination complexes, namely tetrakis(µ-3,4-dimethoxy-trans-cinnamato-κ(2)O:O')bis[[4-(1H-pyrazol-3-yl)pyridine]zinc(II)] heptahydrate, [Zn2(C11H11O4)4(C8H7N3)2]·7H2O or [Zn2(Dmca)4(L1)2]·7H2O, (I), and catena-poly[[bis(3,4-dimethoxy-trans-cinnamato-κO)zinc(II)]-µ-4,4'-bipyridine-κ(2)N:N'], [Zn(C11H11O4)2(C10H8N2)]n or [Zn(Dmca)2(L2)]n, (II). The Zn(II) centres in the two compounds display different coordination polyhedra. In complex (I), the Zn(II) cation is five-coordinated with a pseudo-square-pyramidal geometry, while in complex (II) the Zn(II) cation sits on a twofold axis and adopts a distorted tetrahedral coordination environment. Complex (I) features a centrosymmetric binuclear paddle-wheel-like structure, while complex (II) shows a chain structure. This study emphasizes the significant effect of the coordination mode of both carboxylate-group and N-donor coligands on the formation of complex structures.

Synthesis and crystal structures of ethanol-coordinated molybdenum(VI) oxo complexes with tridentate hydrazone ligands.

Reaction of [MoO2(acac)2] (where acac = acetylacetonate) with two similar hydrazone ligands in ethanol yielded two ethanol-coordinated mononuclear molybdenum(VI) oxo complexes with general formula [MoO2L(EtOH)], where L = L1 = (N'-(3,5-dibromo-2-hydroxybenzylidene)-4-nitrobenzohydrazide (H2L1), and L = L2 = (N'-(3,5-dibromo-2-hydroxybenzylidene)-2-fluorobenzohydrazide (H2L2). Crystal and molecular structures of the complexes were determined by single crystal X-ray diffraction method. All of the investigated compounds were further characterized by elemental analysis and FT-IR spectra. Single crystal X-ray structural studies indicate that the hydrazone ligands coordinate to the MoO2 cores through enolate oxygen, phenolate oxygen and azomethine nitrogen. The Mo atoms in both complexes are in octahedral coordination. Thermal stability of the complexes has also been studied.

(E)-4-Chloro-N-[4-(methyl-sulfon-yl)benzyl-idene]aniline.

In the crystal structure of the title compound, C(14)H(12)ClNO(2)S, the mol-ecules display a trans conformation with respect to the C=N double bond. The dihedral angle between the methyl-sulfonyl benzene and chloro-benzene rings is 59.59 (8)°. The crystal packing is stabilized by weak C-H⋯O inter-actions and by π-π stacking inter-actions between inversion-related methyl-sulfonyl benzene rings [centroid-centroid distance = 3.8579 (11) Å].

2,3-Dibromo-6-meth-oxy-4-[(phenethyl-amino)-methyl-idene]cyclo-hexa-2,5-dien-1-one methanol monosolvate.

In the title compound, C(16)H(15)Br(2)NO(2)·CH(4)O, the mean planes of the substituted cyclo-hexa-2,5-dien-1-one and phenyl rings are almost parallel [dihedral angle = 7.84 (4)°]. The crystal packing is stabilized by N-H⋯O hydrogen bonds generating infinite [101] chains. The methanol solvent mol-ecules are connected with the main species by O-H⋯O inter-actions.

5-Bromo-2-meth-oxy-4-{[(4-meth-oxy-phen-yl)imino]-meth-yl}phenol monohydrate.

The crystal structure of the title compound, C(15)H(14)BrNO(3)·H(2)O, has a trans configuration about the central C=N double bond. An intra-molecular O-H⋯O hydrogen bond occurs in the main mol-ecule. The crystal packing is stabilized by strong O-H⋯O and O-H⋯N hydrogen bonds.

4-[(E)-(3-Chloro-4-methyl-phen-yl)imino-meth-yl]-2-methoxy-3-nitro-phenyl acetate.

The title compound, C(17)H(15)ClN(2)O(5), displays a trans-configuration with respect to the C=N double bond. The mol-ecule is twisted, the dihedral angle between the mean planes of the two benzene rings being 18.70 (12)°. The nitro, meth-oxy and acetyl groups are oriented at 80.70 (11), 35.2 (2) and 72.35 (10)°, respectively, to the benzene ring to which they are bonded. The crystal structure is stabilized by weak C-H⋯O hydrogen-bonding contacts.

rac-Ethyl 2-amino-3-hy-droxy-3-[4-(methyl-sulfon-yl)phen-yl]propano-ate.

In the title compound, C(12)H(17)NO(5)S, the orientations of the 2-ethyl-2-amino-3-hy-droxy-propano-ate group and the 4-methyl-sulfonyl moiety towards the aromatic ring are periplanar and (-)-anti-clinal, respectively. In the crystal packing, the dominant inter-action is O-H⋯N hydrogen bonding, which generates a chain running along [100]. N-H⋯O and C-H⋯O interactions are also observed.

N-[(E)-4-(Methyl-sulfon-yl)benzyl-idene]-3-nitro-aniline.

In the title compound, C(14)H(12)N(2)O(4)S, the dihedral angle between the two aromatic rings is 35.65 (12)°. The crystal packing is stabilized by weak C-H⋯O hydrogen bonds and aromatic π-π ring stacking inter-actions [minimum ring centroid separation = 3.697 (3) Å].

2-Aza-niumyl-4-(ethyl-carbamo-yl)butano-ate: the zwitterionic form of the amino acid theanine.

In the title zwitterion, C(7)H(14)N(2)O(3), the ethyl-amino and the 5-oxo groups are positionally disordered with occupancy ratios of 0.50:0.50 and 0.70:0.30, respectively. The terminal ethyl -CH(3) group undergoes considerable thermal motion. In the crystal, mol-ecules are linked via N-H⋯O hydrogen bonds, forming a two-dimensional arrangement propagating in the bc plane.

(E)-N-[4-(Methyl-sulfon-yl)benzyl-idene]aniline.

The mol-ecule of the title compound, C(14)H(13)NO(2)S, displays a trans configuration with respect to the C=N double bond. The dihedral angle between the two aromatic ring planes is 62.07 (18)°.

4-(Methyl-sulfon-yl)benzaldehyde.

In the crystal of the title compound, C(8)H(8)O(3)S, the mol-ecules are linked into a three-dimensional array by inter-molecular C-H⋯O hydrogen bonds.