Mixed ligand complexes of platinum(II) and palladium(II) with cytokinin-derived compounds Bohemine and Olomoucine: X-ray structure of [Pt(BohH+-N7)Cl(3)].9/5H2O [Boh=6-(benzylamino)-2-[(3-(hydroxypropyl)-amino]-9-isopropylpurine,Bohemine

The new square-planar Pt(II) and Pd(II) complexes with cytokinin-derived compounds Bohemine and Olomoucine, having the formulae [Pt(BohH(+))Cl(3)].H(2)O (1), [Pt(Boh)(2)Cl(2)].3H(2)O (2), [Pt(Boh-H)Cl(H(2)O)(2)].H(2)O (3), [Pt(OloH(+))Cl(3)].H(2)O (4), [Pd(BohH(+))Cl(3)].H(2)O (5), [Pd(Boh)Cl(2)(H(2)O)] (6), [Pd(Boh-H)Cl(H(2)O)].EtOH (7) and [Pd(OloH(+))Cl(3)].H(2)O (8), where Boh=6-(benzylamino)-2-[(3-(hydroxypropyl)amino]-9-isopropylpurine and Olo=6-(benzylamino)-2-[(2-(hydroxyethyl)amino]-9-methylpurine, have been synthesized. The complexes have been characterized by elemental analyses, IR, FAB+ mass, 1H, 13C and 195Pt NMR spectra, and conductivity data. The molecular structure of the complex [Pt(BohH(+)-N7)Cl(3)].9/5H(2)O has been determined by an X-ray diffraction study. Results from physical studies show that both Bohemine and Olomoucine are coordinated to transition metals through the N(7) atom of purine ring in all the complexes. The prepared compounds have been tested in vitro for their possible cytotoxic activity against G-361 (human malignant melanoma), HOS (human osteogenic sarcoma), K-562 (human chronic myelogenous leukemia) and MCF-7 (human breast adenocarcinoma) cell lines and IC(50) values have been also determined for all the complexes. IC(50) values estimated for the Pt(II)-Bohemine complexes (2.1-16 microM) allow us to conclude that they could find utilization in antineoplastic therapy. Thus, from a pharmacological point of view, Pt(II) complexes of Bohemine may represent compounds for a new class of antitumor drugs.     

Synthesis, inhibitory activity and molecular docking studies of two Cu(II) complexes against Helicobacter pylori urease

Two mononuclear copper(II) complexes, [Cu(C(15)H(16)NO(2))(2)] (1) and [Cu(C(6)H(9)N(2)O(4))(2)·3H(2)O] (2·3H(2)O), were synthesised and structurally characterised by single-crystal X-ray analysis. The copper(II) atom adopts a square-planar environment in complex 1, while the geometry in 2·3H(2)O could be described as the distorted square pyramidal. Complexes 1 and 2·3H(2)O were evaluated for their inhibitory activities against Helicobacter pylori (H. pylori) urease in vitro. They both were found to have strong inhibitory activities against H. pylori urease comparable to that of acetohydroxamic acid (AHA). A docking simulation was performed to position 2 into the H. pylori urease active site to determine the probable binding conformation.     

Syntheses and spectroscopic characterization of some phosphoramidates as reversible inhibitors of human acetylcholinesterase and determination of their potency

The ability of phosphoramidates Me2NP(O)(Cl)(p-NHC6H4NO2) 1, Me2NP(O)(p-NHC6H4NO2)2 2, (CH3C6H4O-p)P(O)(p-NHC6H4NO2)2 3 and (CH3C6H40-p)2P(O)(p-NHC6H4NO2) 4 to inhibit human acetylcholinesterase (hAChE) has been evaluated by a modified Ellman's method and spectrophotometric measurements. Results showed that compounds 1 and 2 do not have any inhibitory potency, whereas compounds 3 and 4 were reversible mixed inhibitors. The IC50 values for inhibitors 3 and 4 were 0.143 and 0.581 mM, respectively. The previously unknown compounds 3 and 4 were synthesized and characterized by 1H, 13C, 31P NMR and IR spectroscopy and elemental analysis.     

Inhibitory effects of Mannich bases of heterocyclic chalcones on NO production by activated RAW 264.7 macrophages and superoxide anion generation and elastase release by activated human neutrophils

Some chalcones exert potent anti-inflammatory activities. Mannich bases of heterocyclic chalcones inhibited nitric oxide (NO) production in lipopolysaccharide and interferon-γ stimulated RAW 264.7 macrophages. Also Formyl-Met-Leu-Phe and cytochalasin B induced superoxide anion generation (O2·-) and elastase release in human neutrophils. Mannich bases of heterocyclic chalcone analogs exhibited potent inhibitory effects on NO production with IC(50) values ranges between 10.5 and 0.018 μM, O2·- generation (IC(50) 39.87-0.68 μM) and elastase release (IC(50) 39.74-0.95 μM). Compound 29 (IC(50) 0.055 μM) and 34 (IC(50) 0.018 μM) were showed excellent inhibition on NO production. On the other hand, compounds 2 and 8 showed potent inhibition on O2·- generation and elastase release. Therefore, these four compounds may be new leads for development of anti-inflammatory activities. The structure-activity relationships are also discussed.     

Antifungal activity of organobismuth compounds against the yeast Saccharomyces cerevisiae: structure-activity relationship

Antifungal activity of organobismuth(III) and (V) compounds 1-9 was examined against the yeast, Saccharomyces cerevisiae. A clear structure-activity relationship was observed in these compounds. Thus, triarylbismuth dichlorides 2 [(4-YC6H4)3BiCl2: Y=MeO, F, Cl, CF3, CN, NO2] and halobismuthanes 6 [2-(t)BuSO2C6H4(4-YC6H4)BiX: Y=MeO, Me, H, Cl; X=Cl, Br, I], 7 [Bi(X)(C6H4-2-SO2C6H4-1'-): X=Cl, Br, I], 8 [2-Me2NCH2C6H4(Ph)BiX: X=Cl, Br] and 9 [4-MeC6H4(8-Me2NC10H6-1-)BiCl] showed the growth inhibition effect, while triarylbismuth difluorides 3 [(4-YC6H4)3BiF2] and triarylbismuthanes 1 [(4-YC6H4)3Bi], 4 [2-(t)BuSO2C6H4(4-YC6H4)2Bi] and 5 [4-YC6H4Bi(C6H4-2-SO2C6H4-1'-)] were not active at all irrespective of the nature of the substituents. Generation of the inhibition effect is governed by the facility of nucleophilic reaction at the bismuth center and the Lewis acidic bismuth center is an active site. Of all the bismuth compounds attempted, halobismuthanes 7 derived from diphenyl sulfone exhibited the highest activities. An X-ray crystallographic study of 7a [Bi(Cl)(C6H4-2-SO2C6H4-1'-)] revealed that the bismuth center adopts a seven-coordinated geometry, which is unusual in organobismuth(III) compounds, through the intramolecular and intermolecular coordination between the bismuth and oxygen atoms. The marked inhibition effect of 7 may be attributed to such a highly coordinated geometry, which allows the bismuth center to bind tightly with some biomolecules playing important roles in the growth of S. cerevisiae.     

Coordination compounds derived from the interaction of streptomycin and cobalt, nickel, copper, and calcium salts characterized by 13C NMR and spectroscopic studies. Structure and bonding properties of the streptidine fraction

The coordination compounds of streptomycin (St), Co2(St)Cl4.13H2O (2), Co2(St)(NO3)4.7H2O (3), Ni2(St)Cl4.14H2O (4), Ni2(St)(NO3)4.14H2O (5), Cu2(St)Cl4.6H2O (6), and Ca(St)Cl2.8H2O (7) have been synthesized by the reaction of streptomycin sulfate (1) with three equivalents of the corresponding inorganic salt. The compounds (2)-(7) were characterized by electronic spectroscopy (in the solid state and in solution) by conductivity measurements and by 13C NMR in solution. The reaction of streptomycin with CuCl2 in water hydrolyzed the molecule giving the copper complex of the streptidine fraction (Std), Cu(Std)Cl.H2O (8). This compound was characterized by the same techniques. Detailed x-ray diffraction and 13C NMR studies of streptidine sulfate (9) were carried out.     

Structural models for the interaction of Cd(II) with DNA: trans-[Cd(9-RGH-N7)2(H2O)4]2+

Reactions of Cd(NO(3))(2) with the model nucleobases 9-alkylguanine in water at neutral pH, give the compounds trans-[Cd(9-RGH-N7)(2)(H(2)O)(4)](NO(3))(2)(R=Me, Et), with the 9-alkylguanine ligands bound to the metal cation at the N(7) position. The X-ray structures of both compounds are reported. The six-coordinate Cd(II) complexes consist of a highly regular octahedral geometry in which the two 9-alkylguanine ligands are in a trans position to each other and approximately collinear with the metal cation. In addition, the networks of both compounds show interesting features. Thus, intramolecular H-bonds between O(6) and a coordinated water molecule are present, and self-association of guanines via H-bonding of N(3)-H...N(2) take place, leading to a 1D supramolecular polymeric ribbon. Density functional theory calculations have been applied to both compounds in order to study the stability of N(7) metalated guanine-guanine associations by comparing experimental and theoretical results. The potential relevance with regard to possible Cd(II)-DNA cross-links is briefly discussed.     

Two new megastigmane glycosides, physanosides A and B, from Physalis alkekengi L. var. franchetii, and their effect on NO release in macrophages

Two new megastigmane glycosides, physanosides A and B (1 and 2, resp.), were isolated from Physalis alkekengi L. var. franchetii, together with four known compounds (6S,9R)-roseoside (3), (6S,9S)-roseoside (4), (6R,9S)-3-oxo-alpha-ionol beta-D-glucopyranoside (5), and citroside A (6). Their structures were elucidated on the basis of physicochemical evidence, in-depth NMR spectroscopic analysis, high-resolution mass spectrometry, and CD spectroscopy, and their inhibitory effect on NO production was also examined. Compounds 2 and 3 exhibited strong inhibition on lipopolysaccharide-induced NO release by macrophages with IC(50) values of 9.93 and 7.31 microM, respectively.     

Synthesis,structural characterization and antimicrobial activities of 12 zinc(II) complexes with four thiosemicarbazone and two semicarbazone ligands

Twelve zinc(II) complexes with thiosemicarbazone and semicarbazone ligands were prepared and characterized by elemental analysis, thermogravimetric and differential thermal analysis (TG/DTA), FT-IR and 1H and 13C NMR spectroscopy. Seven three-dimensional structures of zinc(II) complexes were determined by single-crystal X-ray analysis. Their antimicrobial activities were evaluated by MIC against four bacteria (B. subtilis, S. aureus, E. coli and P. aeruginosa), two yeasts (C. albicans and S. cerevisiae) and two molds (A. niger and P. citrinum). The 5- and 6-coordinate zinc(II) complexes with a tridentate thiosemicarbazone ligand (Hatsc), ([Zn(atsc)(OAc)](n) 1, [Zn(Hatsc)(2)](NO(3))(2).0.3H(2)O 2, [ZnCl(2)(Hatsc)] 3 and [Zn(SO(4))(Hatsc)(H(2)O)].H(2)O 4 [Hatsc=2-acetylpyridine(thiosemicarbazone)]), showed antimicrobial activities against test organisms, which were different from those of free ligands or the starting zinc(II) compounds. Especially, complex 2 showed effective activities against P. aeruginosa, C. albicans and moderate activities against S. cerevisiae and two molds. These facts are in contrast to the results that the 5- or 6-coordinate zinc(II) complexes with a tridentate 2-acetylpyridine-4N-morpholinethiosemicarbazone, ([Zn(mtsc)(2)].0.2EtOH 5, the previously reported catena-poly [Zn(mtsc)-mu-(OAc-O,O')](n) and [Zn(NO(3))(2)(Hmtsc)] [Hmtsc=2-acetylpyridine (4N-morpholyl thiosemicarbazone)]), showed no activities against the test microorganisms. The 5- and 6-coordinate zinc(II) complexes with a tridentate 2-acetylpyridinesemicarbazone, ([Zn(OAc)(2)(Hasc)] 6 and [Zn(Hasc)(2)](NO(3))(2) 7 [Hasc=2-acetylpyridine(semicarbazone)]), showed no antimicrobial activities against bacteria, yeasts and molds. Complex [ZnCl(2)(Hasc)] 8, which was isostructural to complex 3, showed modest activity against Gram-positive bacterium, B. subtilis. The 1:1 complexes of zinc(II) with pentadentate thiosemicarbazone ligands, ([Zn(dmtsc)](n) 9 and [Zn(datsc)](n) 10 [H(2)dmtsc=2,6-diacetylpyridine bis(4N-morpholyl thiosemicarbazone) and H(2)datsc=2,6-diacetylpyridine bis(thiosemicarbazone)]), did not inhibit the growth of the test organisms. On the contrary, 7-coordinate zinc(II) complexes with one pentadentate semicarbazone ligand and two water molecules, ([Zn(H(2)dasc)(H(2)O)(2)](OAc)(2).5.3H(2)O 11 and [Zn(H(2)dasc)(H(2)O)(2)](NO(3))(2).H(2)O 12 [H(2)dasc=2,6-diacetylpyridine bis(semicarbazone)]), showed modest to moderate activities against bacteria. Based on the X-ray structures, the structure-activity correlation for the antimicrobial activities was elucidated. The zinc(II) complexes with 4N-substituted ligands showed no antimicrobial activities. In contrast to the previously reported nickel(II) complexes, properties of the ligands such as the ability to form hydrogen bonding with a counter anion or hydrated water molecules or the less bulkiness of the 4N moiety would be a more important factor for antimicrobial activities than the coordination number of the metal ion for the zinc(II) complexes.     

Novel platinum(II) and palladium(II) complexes with cyclin-dependent kinase inhibitors: synthesis, characterization and antitumour activity

The Pt(II) and Pd(II) complexes of the types cis-[Pt(L(1))(2)Cl(2)].H(2)O (1), cis-[Pt(L(2))(2)Cl(2)].3H(2)O (2), trans-[Pd(L(1))(2)Cl(2)].H(2)O (3), trans-[Pd(L(2))(2)Cl(2)].H(2)O (4), trans-[Pd(L(3))(2)Cl(2)].2DMF (5) and trans-[Pd(L(4))(2)Cl(2)].2DMF (6) (L(1)-L(4)=cyclin-dependent kinase inhibitors derived from 6-benzylamino-9-isopropylpurine) have been prepared and characterized. The complexes have been studied by elemental analyses, conductivity measurements, ES+ MS, FT-IR, (1)H, (13)C and (195)Pt NMR spectra, differential scanning calorimetry and thermogravimetric analysis. The molecular structures of L(1), trans-[Pd(L(3))(2)Cl(2)].2DMF (5) and trans-[Pd(L(4))(2)Cl(2)].2DMF (6) have been determined by single crystal X-ray analysis. The complexes have been tested in vitro due to their presumable anticancer activity against the following human cancer cell lines: K-562, MCF7, G-361 and HOS. Satisfying results were obtained for the complex 1 with IC(50) values of 6 microM acquired against G-361 as well as against HOS cell lines. The lowest values of IC(50) were achieved for the complexes 3 and 4 against MCF 7 cell line with IC(50) 3 microM(for 3) and also 3 microM (for 4).     

培养基组分及培养条件对蜡梅花粉萌发及花粉管生长的影响

采用液体培养法研究不同培养基组分和培养条件对蜡梅花粉萌发和花粉管生长的影响。结果表明:(1)PEG-4000是蜡梅花粉离体培养所必需的培养基成分,当培养基中无PEG-4000时,花粉不能正常萌发。(2)培养基内低浓度蔗糖对花粉萌发和花粉管的生长无显著影响,但随着蔗糖浓度的升高,则对花粉萌发和花粉管生长表现出强烈的抑制作用,且浓度越高,抑制效应越强。(3)培养基内其它组分分别在一定浓度范围(0～250g/L PEG-4000、0～50mg/L硼酸、0～30mg/L硝酸钙)内对花粉萌发及花粉管生长有促进作用,但超过上述高限值时则起抑制作用。(4)培养基内镁和钾的浓度对花粉萌发及花粉管生长影响不显著。研究表明,蜡梅最适花粉液体培养基组分为250g/L PEG-4000+50mg/L H3BO3+30mg/L Ca(NO3)2.4H2O,且在pH 5.5、温度15℃和600lx的光照培养条件下蜡梅花粉萌发和花粉管生长最佳。     

Interactions between metal ions and carbohydrates. Syntheses and spectroscopic studies of several lanthanide nitrate-D-galactitol complexes

Two complexes of neutral D-galactitol (C(6)H(14)O(6), G) with terbium nitrate, TbGN(I) and TbGN(II), and one complex with samarium nitrate SmGN were synthesized and characterized. From IR, FIR, THz and luminescence spectra the possible coordinations were suggested, and the single-crystal X-ray diffraction results confirm the spectroscopic conclusions. In TbGN(I) (Tb(NO(3))(3)·C(6)H(14)O(6)·3H(2)O), the Tb(3+) is 9-coordinated with three water molecules and six OH groups from two D-galactitol molecules. Nitrate ions do not coordinate to metal ions, which is different from other reported lanthanide nitrate-D-galactitol complexes. In TbGN(II) and SmGN (Ln(NO(3))(3)·C(6)H(14)O(6)), Ln(3+) is 10-coordinated with six OH groups from two D-galactitol molecules and four oxygen from two bidentate nitrate ions, and one nitrate ion is hydrogen bonded. No water exists in the structures. D-Galactitol molecules provide their 1-, 2- and 3-hydroxyl groups to coordinate with one metal ion and their 4-, 5- and 6-hydroxyl groups to coordinate with another metal ion in the three structures. There is still a new topological structure that can be observed for lanthanide-d-galactitol complexes, which indicates that the coordinations between hydroxyl groups and metal ions are complicated.     

A Study on the Application of C17 Medium for Anther Culture

Media with varied levels of minor elements and KNO3, NH4NO3, KH2PO4, MgSO4·7H2O, CaCl2· 2H2O and Fe-Salts were screened to obtain high yield of callus from wheat anther by using orthogonal tests. Of all the seven minor elements treated, the one without NaMoO4·2H2O and with 11.2 mg/l MnS04·4H2O was found to be the most effective. Among the five kinds of organic materials tested, biotin appear- ed to have the highest influence on the induction frequency of anther callus and its opimum dosage was 1.5 mg/l. Based on these data, C17 medium was developed and its induction frequency of callus with good quality from wheat anther reached 12.19% in the Institute in 1980. The maximum diffrentiation freguency of anther callus obtained was 50% on C17 medium. C17, medium compositions are as follows (Mg/l): 1400 KNO3, 150 CaCl2-2H2O, 150 MgSO4·7H2O, 300 NH4NO3, 400 KH2PO4, 27.85 FeSO4·7H2O, 37,25 Na2-EDTA, 11.2 MnS04·4H2O, 8.6 ZnSO4·7H2O, 6.2 H3BO3, 0.83 KI, 0.025 CuSO4·5H2O, 0.025 CaCl2·: 6H2O, 8 glycine, 0.5 nicotinic acid, 0.5 thiamine hydrochloride and 1.5 biotin. The re- differentiation medium is supplemented with 2 2,4-D+0.5 KT+7000 agar+90000 sucrose, pH5.8. The dedifferentiation supplemented with 0.5 IBA+2 KT+7000 agar+ 30000 sucrose, pH 5.8.     

Protonated nucleobase ligands: synthesis, structure and characterization of 9-methyladeninium hexachloroplatinate and pentachloro(9-methyladeninium)platinum(IV)

Na(2)[PtCl(6)] was found to react with (9-MeAH)Cl(.)H(2)O (2) (9-MeA=9-methyladenine) in aqueous solution yielding (9-MeAH)(2)[PtCl(6)](.)2H(2)O (3). The same compound was obtained from hexachloroplatinic acid and 9-methyladenine. Performing this reaction at 60 degrees C, complex formation took place yielding the 9-methyladeninium complex [PtCl(5)(9-MeAH)](.)2H(2)O (4a). An analogous complex, [PtCl(5)(9-MeAH)](.)1/2(18C6)(.)H(2)O (4b, 18C6=crown ether 18-crown-6), was formed in the reaction of aquapentachloroplatinic acid (H(3)O)[PtCl(5)(H(2)O)](.)2(18C6)(.)6H(2)O (1) with 9-methyladenine in 1:1 ratio. All complexes were isolated in moderate to good yields as yellow powder (4b) and crystals (3, 4a), respectively. They were fully characterized by microanalysis, IR and NMR ((1)H, (13)C, (195)Pt) spectroscopies, and in part (2, 3, 4a) also by single-crystal X-ray diffraction analysis. Molecular structure of complex 4a exhibited that the 9-methyladeninium ligand is N1 protonated and coordinated through N7 to platinum(IV).     

Synthesis of N-substituted piperidine-4-(benzylidene-4-carboxylic acids) and evaluation as inhibitors of steroid-5alpha-reductase type 1 and 2

The synthesis of N-substituted piperidine-4-(benzylidene-4-carboxylic acids) is described [benzoyl (1), benzyl (2), adamantanoyl (3), cyclohexanoyl (4), cyclohexylacetyl (5), diphenylacetyl (6), dicyclohexylacetyl (7), 2-propylpentanoyl (8), diphenylcarbamoyl (9), trimethylacetyl (10), 3,3-dimethylacryloyl (11), dicyclohexylacetyl derivative of the benzyl compound (12)]. Compounds were tested for inhibitory activity toward 5alpha-reductase isozymes 1 and 2 in human and rat. The test compounds inhibited 5alpha-reductase, showing a broad range of inhibitory potencies. In rat, compounds 6 (IC50 = 3.44 and 0.37 microM for type 1 and 2, respectively) and 9 (IC50=0.54 and 0.69 microM for type 1 and 2, respectively) displayed the best inhibition toward both isozymes. Compound 7 showed a strong inhibition toward type 2 human and rat enzyme (IC50 = 60 and 80 nM) but only a moderate activity versus type 1 enzyme (IC50 approximately 10 microM for rat and human enzyme). In vivo, selected compounds reduced prostate weights in castrated testosterone treated rats.     

High conservation of the Set1/Rad6 axis of histone 3 lysine 4 methylation in budding and fission yeasts

Histone 3 lysine 4 (H3 Lys(4)) methylation in Saccharomyces cerevisiae is mediated by the Set1 complex (Set1C) and is dependent upon ubiquitinylation of H2B by Rad6. Mutually exclusive methylation of H3 at Lys(4) or Lys(9) is central to chromatin regulation; however, S. cerevisiae lacks Lys(9) methylation. Furthermore, a different H3 Lys(4) methylase, Set 7/9, has been identified in mammals, thereby questioning the relevance of the S. cerevisiae findings for eukaryotes in general. We report that the majority of Lys(4) methylation in Schizosaccharomyces pombe, like in S. cerevisiae, is mediated by Set1C and is Rad6-dependent. S. pombe Set1C mediates H3 Lys(4) methylation in vitro and contains the same eight subunits found in S. cerevisiae, including the homologue of the Drosophila trithorax Group protein, Ash2. Three additional features of S. pombe Set1C each involve PHD fingers. Notably, the Spp1 subunit is dispensable for H3 Lys(4) methylation in budding yeast but required in fission yeast, and Sp_Set1C has a novel proteomic hyperlink to a new complex that includes the homologue of another trithorax Group protein, Lid (little imaginal discs). Thus, we infer that Set1C is highly conserved in eukaryotes but observe that its links to the proteome are not.     

Crystal structure, solid state and solution characterisation of copper(II) coordination compounds of ethyl 5-methyl-4-imidazolecarboxylate (emizco)

The synthesis and characterisation of the following compounds derived from the biological relevant compound ethyl 5-methyl-4-imidazolecarboxylate (emizco) (1): [Cu(emizco)Cl2] (2), [Cu(emizco)2Cl2] (3), [Cu(emizco)2Br2] (4), [Cu(emizco)2(H2O)2](NO3)2 (5) and [Cu(emizco)4](NO3)2 (6), is presented. These compounds were characterised by IR and UV spectroscopic techniques, in addition the crystal structures of compounds 1-5 were determined. For complexes 2-5, emizco is coordinated as a bidentate ligand, through the oxygen atom of the carboxylate moiety and the nitrogen atom of the imidazolic ring. Different geometries are stabilised: compound 2 includes a pentacoordinated square pyramidal metal centre, while 3-5 are derived from octahedral geometry. Halide compounds 3 and 4 show a cis-octahedral arrangement, which is not very common on [CuN2O2X2] systems, while 5 stabilises the trans-octahedral isomer. Compound 6 displays a square planar geometry. Finally, hydrolysis of emizco to its corresponding carboxylic acid (mizco), allowed the preparation of another square planar complex 7, identified as [Cu(mizco)2] 0.5H2O. Solution studies of these compounds indicate that emizco is not substituted from the coordination sphere, remaining as a bidentate ligand. Halides are substituted by water molecules, changing from cis octahedral to the trans-[Cu(emizco)2(H2O)2]2+ isomer.     

Synthesis, crystal structures, in vitro biological evaluation of zinc(II) and bismuth(III) complexes of 2-acetylpyrazine N(4)-phenylthiosemicarbazone

Two metal complexes formulated as [Zn(L)(2)](2)·H(2)O (1) and [Bi(L)(NO(3))(2)(CH(3)OH)] (2), where HL=2-acetylpyrazine N(4)-phenylthiosemicarbazone, have been synthesized and characterized by elemental analysis, IR, MS, NMR and single-crystal X-ray diffraction studies. Biological studies, carried out in vitro against selected bacteria and the K562 leukemia cell lines, respectively, have shown that the free ligand and its two complexes may be endowed with important biological properties, especially HL with MIC=3.90 μg/mL against Pseudomonas aeruginosa, the zinc(II) complex 1 with IC(50)=1.0 μM against K562 leukemia cell lines, respectively. The compounds HL and 1 may exert their cytotoxicity activity via induced loss of mitochondria membrane potential (MMP).     

Possibility of the involvement of 9H-pyrido[3,4-b]indole (norharman) in carcinogenesis via inhibition of cytochrome P450-related activities and intercalation to DNA

This study investigated the inhibitory effect of 9H-pyrido[3,4-b]indole (norharman), one of the naturally occurring beta-carbolines, on cytochrome P450 (CYP)-related activities and the relationship between its inhibitory effect, its intercalation to DNA, and its comutagenic effect. Norharman reduced the mutagenicities of heterocyclic amines (HCAs) containing 2-amino-6-methyldipyrido[1,2-a:3',2'-d]imidazole (Glu-P-1), aflatoxin B1, benzo[a]pyrene (BP), and some nitrosamines in the presence of 10 microl liver S9 (20.9 microg protein/ml) from polychlorinated biphenyl-treated rats. Norharman inhibited microsomal CYP-related enzyme activities and CO-binding to the CYP heme (50% inhibitory concentration (IC50), 0.07-6.4 microg/ml). It also inhibited the formation of 3-hydroxyamino-6-methyldipyrido[1,2-a:3',2'-d]imidazole (N-OH-Glu-P-1) and was a noncompetitive-inhibitor of CYP1A-related activities, while it enhanced the direct mutagenicity of N-OH-Glu-P-1 (50% effective concentration, 25.0 microg/ml) and inhibited topo I activity (IC50, 31.0 microg/ml). In the presence of norharman, S9 up to 100 microl incrementally enhanced the mutagenicities of HCAs, BP and dimethylnitrosamine. These data clarified that norharman acts as an inhibitor of the CYP-mediated biotransformation of Glu-P-1 via inhibition of O2-binding to CYP heme, and its inhibition of CYP enzymes occurs at much lower concentration than that for its intercalation to DNA. It is indicated that norharman's inhibitory effect on CYP results in the inhibition of excess metabolism by S9 and this is more likely the mechanism for comutagenic action than the intercalation. Norharman's inhibition of CYP and its enhancement of the N-OH-Glu-P-1 mutagenicity suggest that beta-carbolines modulate chemical carcinogenesis by controlling the xenobiotic metabolism and by intercalating to DNA.     

Biological and cytoselective anticancer properties of copper(II)-polypyridyl complexes modulated by auxiliary methylated glycine ligand

A series of ternary copper(II)-1,10-phenanthroline complexes with glycine and methylated glycine derivatives, [Cu(phen)(aa)(H(2)O)]NO(3)·xH(2)O 1-4 (amino acid (aa): glycine (gly), 1; DL: -alanine (DL: -ala), 2; 2,2-dimethylglycine (C-dmg), 3; sarcosine (sar), 4), were synthesized and characterized by FTIR, elemental analysis, electrospray ionization-mass spectra (ESI-MS), UV-visible spectroscopy and molar conductivity measurement. The determined X-ray crystallographic structures of 2 and 3 show each to consist of distorted square pyramidal [Cu(phen)(aa)(H(2)O)](+) cation, a nitrate counter anion, and with or without lattice water, similar to previously reported structure of [Cu(phen)(gly)(H(2)O)]NO(3)·1?H(2)O. It is found that 1-4 exist as 1:1 electrolytes in aqueous solution, and the cationic copper(II) complexes are at least stable up to 24?h. Positive-ion ESI-MS spectra show existence of only undissociated [Cu(phen)(aa)](+) species. Electron paramagnetic resonance, gel electrophoresis, fluorescence quenching, and restriction enzyme inhibition assay were used to study the binding interaction, binding affinity and selectivity of these complexes for various types of B-form DNA duplexes and G-quadruplex. All complexes can bind selectively to DNA by intercalation and electrostatic forces, and inhibit topoisomerase I. The effect of the methyl substituents of the coordinated amino acid in the above complexes on these biological properties are presented and discussed. The IC(50) values (24?h) of 1-4 for nasopharyngeal cancer cell line HK1 are in the range 2.2-5.2?μM while the corresponding values for normal cell line NP69 are greater than 13.0?μM. All complexes, at 5?μM, induced 41-60?% apoptotic cell death in HK1 cells but no significant cell death in NP69 cells.