(Z)-3-[(2-Amino-benz-yl)amino]-1-phenyl-but-2-en-1-one.

In the title compound, C17H18N2O, the aromatic rings are almost normal to one another, making a dihedral angle of 89.00 (8)°. There is an intra-molecular N-H⋯O hydrogen bond in the mol-ecule enclosing an S(6) ring motif. In the crystal, mol-ecules are linked by N-H⋯O hydrogen bonds, forming chains along [010].

(Z)-3-(2-Amino-anilino)-1-phenyl-but-2-en-1-one.

In the title compound, C16H16N2O, the phenyl and 2-amino-phenyl rings are almost perpendicular to one another, with a dihedral angle of 82.77 (8)°. There is an intra-molecular N-H⋯O hydrogen bond in the mol-ecule. In the crystal, mol-ecules are linked via N-H⋯O hydrogen bonds forming chains along [001]. There are also C-H⋯π inter-actions present, linking the chains to form a three-dimensional structure.

Evaluation of antioxidant efficacy of vanadium-3-hydroxyflavone complex in streptozotocin-diabetic rats.

Since 1985, when Heyliger et al., first demonstrated that oral administration of sodium orthovanadate (0.8mg/ml) to STZ induced diabetic rats resulted in normoglycemia, numerous extensive studies have been reported on the antidiabetic actions of vanadium. The acceptance of vanadium compounds as promising therapeutic antidiabetic drugs has been slowed due to the concern for chronic toxicity associated with vanadium accumulation. In order to circumvent the toxic effects of vanadium, a combinational approach wherein a novel V3HF complex was synthesized, characterized and its toxic as well as antidiabetic potential were evaluated in STZ diabetic rats. Experimental and clinical studies suggest that hyperglycemia-induced oxidative stress primarily contributes to the pathogenesis and progression of both primary as well as secondary complications of diabetes. It is possible to reduce the risks caused by excessive generation of free radicals by either enhancing the body's natural antioxidant defenses or by supplementing with proven antioxidants. The present study was aimed to study the role of V3HF complex on hyperglycemia mediated oxidative stress in STZ-diabetic rats and the results indicate that the complex improves pancreatic beta cell function. Histological and ultrastructural studies also evidenced that the complex protect the beta cells from hyperglycemia-induced oxidative stress.

A novel insulin mimetic vanadium-flavonol complex: synthesis, characterization and in vivo evaluation in STZ-induced rats.

Since 1985, when Heyliger et al., first demonstrated a serendipitous discovery that oral administration of 0.8 mg/ml of sodium orthovanadate in drinking water to streptozotocin-induced diabetic rats resulted in normoglycemia, numerous extensive studies have been pursued on the anti-diabetic and insulinomimetic actions of vanadium. The acceptance of vanadium compounds as promising therapeutic antidiabetic agents has been slowed due to the concern for chronic toxicity associated with vanadium accumulation. In order to circumvent the toxic effects of vanadium, we have taken up a combinational approach wherein a novel vanadium-flavonol complex was synthesized, characterized and its toxic as well as insulin mimetic potential was evaluated in STZ-induced experimental diabetes in rats. The results indicate that the complex is non-toxic and possess anti-diabetic activity.

DNA targeting polyaza macrobicyclic dizinc(II) complexes promoting high in vitro caspase dependent anti-proliferative activity against human carcinoma cancer cells.

A series of macrobicyclic dizinc(II) complexes [Zn(2)L(1-2)B](ClO(4))(4) (1-6) have been synthesized and characterized (L(1-2) are polyaza macrobicyclic binucleating ligands, and B is the N,N-donor heterocyclic base (viz. 2,2'-bipyridine (bipy) and 1,10-phenanthroline (phen)). The DNA and protein binding, DNA hydrolysis and anticancer activity of these complexes were investigated. The interactions of complexes 1-6 with calf thymus DNA were studied by spectroscopic techniques, including absorption, fluorescence and CD spectroscopy. The DNA binding constant values of the complexes were found to range from 2.80 × 10(5) to 5.25 × 10(5) M(-1), and the binding affinities are in the following order: 3 > 6 > 2 > 5 > 1 > 4. All the dizinc(II) complexes 1-6 are found to effectively promote the hydrolytic cleavage of plasmid pBR322 DNA under anaerobic and aerobic conditions. Kinetic data for DNA hydrolysis promoted by 3 and 6 under physiological conditions give observed rate constants (k(obs)) of 5.56 ± 0.1 and 5.12 ± 0.2 h(-1), respectively, showing a 10(7)-fold rate acceleration over the uncatalyzed reaction of dsDNA. Remarkably, the macrobicyclic dizinc(II) complexes 1-6 bind and cleave bovine serum albumin (BSA), and effectively promote the caspase-3 and caspase-9 dependent deaths of HeLa and BeWo cancer cells. The cytotoxicity of the complexes was further confirmed by lactate dehydrogenase enzyme levels in cancer cell lysate and content media.

A series of oxyimine-based macrocyclic dinuclear zinc(II) complexes enhances phosphate ester hydrolysis, DNA binding, DNA hydrolysis, and lactate dehydrogenase inhibition and induces apoptosis.

A symmetrical macrocyclic dizinc(II) complex (1) has been synthesized by using the ligand (L(1)) [µ-11,24-dimethyl-4,7,16,19-tetraoxa-3,8,15,20-tetraazatricyclo-[20.3.1.1(10,13)] heptacosa-1(25),2,7,9,11,13(27),14,20,22(26),23-decaene-26,27-diol]. A series of unsymmetrical macrocyclic dizinc(II) complexes (2-6) has been synthesized by Schiff base condensation of bicompartmental mononuclear complex [ZnL] [µ-3,16-dimethyl-8,11-dioxa-7,12-diazadicyclo-[1.1(14,18)] heptacosa-1,3,5(20),6,12,14,16,18(19)-octacaene-19,20-diolato)zinc(II)] with various diamines like 1,2-diamino ethane (L(2)), 1,3-diamino propane (L(3)), 1,4-diamino butane (L(4)), 1,2-diamino benzene (L(5)), and 1,8-diamino naphthalene (L(6)). The ligand L(1) and all the zinc(II) complexes were structurally characterized. To corroborate the consequence of the aromatic moiety in comparison to the aliphatic moiety present in the macrocyclic ring on the phosphate ester hydrolysis, DNA binding and cleavage properties have been studied. The observed first order rate constant values for the hydrolysis of 4-nitrophenyl phosphate ester reaction are in the range from 2.73 × 10(-2) to 9.86 × 10(-2) s(-1).The interactions of complexes 1-6 with calf thymus DNA were studied by spectroscopic techniques, including absorption, fluorescence, and circular dichroism spectroscopy. The DNA binding constant values of the complexes were found in the range from 1.80 × 10(5) to 9.50 × 10(5) M(-1), and the binding affinities are in the following order: 6 > 5 > 1 > 2 > 3 > 4. All the dizinc(II) complexes 1-6 effectively promoted the hydrolytic cleavage of plasmid pBR322 DNA under anaerobic and aerobic conditions. Kinetic data for DNA hydrolysis promoted by 6 under physiological conditions give the observed rate constant (k(obs)) of 4.42 ± 0.2 h(-1), which shows a 10(8)-fold rate acceleration over the uncatalyzed reaction of ds-DNA. The comparison of the dizinc(II) complexes 1-6 with the monozinc(II) complex [ZnL] indicates that the DNA cleavage acceleration promoted by 1-6 are due to the efficient cooperative catalysis of the two close proximate zinc(II) cation centers. The ligand L(1), dizinc(II) complexes 1, 3, and 6 showed cytotoxicity in human hepatoma HepG2 cancer cells, giving IC(50) values of 117, 37.1, 16.5, and 8.32 µM, respectively. The results demonstrated that 6, a dizinc(II) complex with potent antiproliferative activity, is able to induce caspase-dependent apoptosis in human cancer cells. Cytotoxicity of the complexes was further confirmed by the lactate dehydrogenase enzyme level in HepG2 cell lysate and content media.

Phosphatase-like activity, DNA binding, DNA hydrolysis, anticancer and lactate dehydrogenase inhibition activity promoting by a new bis-phenanthroline dicopper(II) complex.

A new bis-phenanthroline dicopper(II) complex has been synthesized and characterized by elemental analysis and spectroscopic methods. The molecular structure of the dinuclear Cu(II) complex [Cu(2)(µ-CH(3)COO)(µ-H(2)O)(µ-OH)(phen)(2)](2+) (phen = 1,10-phenanthroline) (1) was determined by single crystal X-ray diffraction technique. The coordination environment around each Cu(II) ion in complex 1 can be described as slightly distorted square pyramidal geometry. The distance between the CuCu centers in the complex is found to be 2.987 Å. The electronic, redox, phosphate hydrolysis, DNA binding and DNA cleavage have been studied. The antiproliferative effect of complex 1 was confirmed by the lactate dehydrogenase (LDH) enzyme level in MCF-7 cancer cell lysate and content media. The dicopper(II) complex inhibited the LDH enzyme as well as the growth of the human breast cancer MCF7 cell line at an IC(50) value of 0.011 µg ml(-1). The results strongly suggest that complex 1 is a good cancer therapeutic agent. Electrochemical studies of complex 1 showed an irreversible, followed by a quasi-reversible, one electron reduction processes between -0.20 to -0.8 V. Michaelis-Menten kinetic parameters for the hydrolysis of 4-nitrophenyl phosphate by complex 1 are k(cat) = 3.56 × 10(-2) s(-1) and K(M) = 4.3 × 10(-2) M. Complex 1 shows good binding propensity to calf thymus DNA, with a binding constant value of 1.3 (±0.13) × 10(5) M(-1) (s = 2.1). The size of the binding site and viscosity data suggest a DNA intercalative binding nature of the complex. Complex 1 shows efficient hydrolytic cleavage of supercoiled pBR322-DNA in the dark and in the absence of any external reagents, as demonstrated by the T4 ligase experiment. The pseudo-Michaelis-Menten kinetic parameters for DNA hydrolysis by complex 1 are k(cat) = 1.27 ± 0.4 h(-1) and K(M) = 7.7 × 10(-2) M.

Structural, electrochemical, phosphate-hydrolysis, DNA binding and cleavage studies of new macrocyclic binuclear nickel(II) complexes.

New macrocyclic binuclear nickel(ii) complexes have been synthesized by using the bicompartmental mononuclear complex [NiL] [3,30-((1E,7E)-3,6-dioxa-2,7-diazaocta-1,7-diene-1,8-diyl)bis(3-formyl-5-methyl-2-diolato)nickel(II)] with various diamines like 1,2-bis(aminooxy)ethane (L(1)), 1,2-diamino ethane (L(2)), 1,3-diamino propane (L(3)), 1,4-diamino butane (L(4)), 1,2-diamino benzene (L(5)), and 1,8-diamino naphthalene (L(6)). The complexes were characterized by elemental analysis and spectroscopic methods. The molecular structures of the symmetrical binuclear complex [Ni(2)L(1)(H(2)O)(4)](ClO(4))(2) (1) and unsymmetrical binuclear complex [Ni(2)L(3)(H(2)O)(4)](ClO(4))(2).(H(2)O)(4) (3) were determined by single-crystal X-ray diffraction. The geometry around both the nickel(II) ions in each molecule is a slightly distorted octahedral. The distance between the Ni...Ni centers for complex 1 is 3.039 A and for complex 3 is 3.059 A. The influence of the coordination geometry and the ring size of the binucleating ligands on the electronic, redox, phosphate hydrolysis, DNA binding and cleavage properties have been studied. Electrochemical studies of the complexes show two quasi-reversible one electron reduction processes between -0.49 to -1.69 V. The reduction potential of the binuclear Ni(II) complexes shifts towards anodically upon increasing the macrocyclic ring size. The observed first order rate constant values for the hydrolysis of 4-nitrophenyl phosphate reaction are in the range from 8.69 x 10(-3) to 1.85 x 10(-2) s(-1). The complexes show good binding propensity to calf thymus DNA giving binding constant values in the range from 1.4 x 10(4) to 17.5 x 10(4) M(-1). The absorption, fluorescence and CD spectral data suggests that the complexes are strongly interacting with DNA. These complexes display hydrolytic cleavage of supercoiled pBR322DNA in the presence of H(2)O(2) at pH 7.2 and 37 degrees C. The hydrolytic cleavage of DNA by the complexes is supported by the evidence from free radical quenching and T4 ligase ligation. The pseudo-Michaelis-Menten kinetic parameters k(cat) = 1.27 +/- 0.4 h(-1) and K(M) = 7.7 x 10(-2) M for naphthalene diimine containing macrocyclic binuclear nickel(II) complex, (6) were obtained.

Protective effect of macrocyclic binuclear oxovanadium complex on oxidative stress in pancreas of streptozotocin induced diabetic rats.

Chronic hyperglycemia in diabetes is a major causative factor of free radical generation which further leads to many secondary diabetic complications via the damage to cellular proteins, membrane lipids, nucleic acids and eventually to cell death. Recently we have reported on the hypoglycemic efficacy of a new macrocyclic binuclear oxovanadium complex and its non-toxic nature. This study focuses on the effect of the above complex in ameliorating oxidative stress in the pancreas of diabetic rats. Streptozotocin induced diabetic rats were treated orally with the vanadium complex (5 mg/kg/body weight) for 30 days and the level of pancreatic antioxidants and lipid peroxides were determined. Treatment with the macrocyclic binuclear oxovanadium complex decreased the lipid peroxides and the antioxidant enzymes such as superoxide dismutase, catalase and glutathione peroxidase to near control levels. Histological examinations also revealed the protective effect of the complex on pancreatic beta cells. The results demonstrate the protective effect of the macrocyclic binuclear oxovanadium complex on the pancreatic antioxidant status.

Effect of macrocyclic binuclear oxovanadium complex on tissue defense system in streptozotocin-induced diabetic rats.

BACKGROUND: Oxidative stress plays an important role in chronic complications of diabetes mellitus and hence the regulation of free radicals is essential in the treatment of diabetes. The protective effect of a new macrocyclic binuclear oxovanadium complex on antioxidant defense systems of liver and kidney was examined in streptozotocin-induced experimental diabetes in rats. METHODS: The levels of lipid peroxides, glutathione and the activities of superoxide dismutase, catalase, glutathione peroxidase and glutathione-S-transferase were assayed according to standard procedures in the liver and kidney of control and experimental groups of rats. RESULTS: A significant decrease (p < 0.05) was observed in both the glutathione content and in the activities of antioxidant enzymes such as superoxide dismutase, catalase, glutathione peroxidase and a concomitant increase in the level of lipid peroxides in diabetic rats. The observed alterations in the antioxidant status of tissues reverted back to near normal levels after the oral administration of macrocyclic vanadium complex at a dose of 5 mg/kg body weight/rat/day for a period of 30 days. CONCLUSION: The normoglycemic efficacy of the vanadium complex alleviates oxidative stress in streptozotocin-induced diabetes in rats.