Copper(II) Schiff base coordination compounds of dien with heterocyclic aldehydes and 2-amino-5-methyl-thiazole: synthesis, characterization, antiproliferative and antibacterial studies. Crystal structure of CudienOOCl2

A new series of coordination compounds of the starting materials [Cu(dienX(2)Y(2))] and their adducts [Cu(dienXXY(2))(2a-5mt)] (where dien=diethylenetriamine, dienXX=Schiff bases of diethylenetriamine with 2-furaldehyde or 2-thiophene-carboxaldehyde, X=O, S, Y=Cl, Br, NO(3) and 2a-5mt=2-amino-5-methylthiazole) were synthesized by stepwise reactions and their structures were established by C, H, N, Cu analysis, spectroscopic, magnetic and molar conductivity measurements. The isolated compounds are monomers, paramagnetic and electrolytic compounds of the type 1:1. In all cases, the pentadentate Schiff base (dienXX) is bonded in a tridentate fashion through the 3 N atoms. In the CudienXXY(2) compounds the coordination sphere is completed by two Cl or Br or NO(3) groups in a square pyramidal arrangement. The proposed structure for this type of compound was further supported by X-ray diffraction analysis of the compound [Cu(dienOO)Cl(2)]. Its basal plane consists of three Cu-N contacts [2.017(2), 2.025(2) and 2.012(2) A] from dienOO, and the Cl(1) atom, while the Cl(2) atom possesses the apical position, the relevant distances being 2.2732(7) A for Cu-Cl(1) and 2.6051(7) A Cu-Cl(2). In the CudienX(2)Y(2).2a-5mt adducts the coordination sphere of copper is further completed by the nitrogen ring atom of the 2a-5mt, forming an octahedral configuration. The study of the biological activity of the compounds synthesized against a panel of different normal and cancer cell lines (MRC5, HeLa, MCF7, HT-29, OAW42, T47D) and bacteria (E. coli, B. cereus, B. subtilis) showed that the adducts of the type [Cu(dienXXY(2))(2a-5mt)] exhibit increased activity both in cancer cells and in bacteria, compared to the starting material of type [Cu(dienXXY(2))].     

In vivo anticancer, anti-inflammatory, and toxicity studies of mixed-ligand Cu(II) complexes of dien and its Schiff dibases with heterocyclic aldehydes and 2-amino-2-thiazoline. Crystal structure of [Cu(dien)(Br)(2a-2tzn)](Br)(H(2)O)

A new series of complexes of the type [Cu(dien)(2a-2tzn)Y(2)] and [Cu(dienXX)(2a-2tzn)Y(2)], where dien=diethylenetriamine and dienXX=Schiff dibase of diethylenetriamine formed with 2-furaldehyde (dienOO), 2-thiophenecarboxaldehyde (dienSS), or pyrrol-2-carboxaldehyde (dienNN); Y=Cl, Br or NO(3); and 2a-2tzn=2-amino-2-thiazoline, were synthesized and their structure established by C, H, N and Cu analysis; IR and electronic spectra; magnetic susceptibility; and molar conductivity. The isolated complexes are monomers, paramagnetic, and electrolytes of types 1:1 or 1:2. In both types of solid state complexes, [Cu(dien)(2a-2tzn)Y(2)] and [Cu(dienXX)(2a-2tzn)Y(2)], dien and its Schiff dibases are bonded to Cu(II) in a tridentate fashion through 3N atoms. The coordination sphere is completed by the endocyclic nitrogen of the thiazoline moiety and by two Cl, Br, or NO(3) groups with distorted octahedral geometry. The proposed structure of these compounds was supported by X-ray analysis of [Cu(dien)(Br)(2a-2tzn)](Br)(H(2)O). The coordination polyhedron around the copper atom can be described as a distorted square pyramid [Cu(dien)(Br)(2a-2tzn)](+). Its basal plane is occupied by the four nitrogen atoms of the dien and thiazoline ligands with Cu-N distances ranging between 1.996(6) and 2.032(3)A, and the axial position is occupied by one of the two bromine atoms (Br1) with a Cu1-Br1 bond distance of 2.782(1)A. The second bromine atom (Br2) is 4.694(2)A from the copper atom, which exists as a discrete anion and is responsible for the cationic nature of the complex. Results regarding toxicity, antitumor, and anti-inflammatory activities of the investigated compounds are promising and allow the selection of a lead compound for further biological studies.     

Synthesis, structure, and nuclease properties of several binary and ternary complexes of copper(II) with norfloxacin and 1,10 phenantroline

Three new binary Cu(II) complexes of norfloxacin have been synthesized and characterized. We also report the synthesis, characterization and X-ray crystallographic structures of a new binary compound, [Cu(HNor)(2)]Cl(2).2H(2)O (2) and two new ternary complexes norfloxacin-copper(II)-phen, [Cu(Nor)(phen)(H(2)O)](NO(3)).3H(2)O (4), and [Cu(HNor)(phen)(NO(3))](NO(3)).3H(2)O (5). The structure of 2 consists of two crystallographically independent cationic monomeric units of [Cu(HNor)(2)](2+), chloride anions, and uncoordinated water molecules. The Cu(II) ion is placed at a center of symmetry and is coordinated to two norfloxacin ligands which are related through the inversion center. The structures of 4 and 5 consist of cationic units ([Cu(Nor)(phen)(H(2)O)](+) for 4 and [Cu(HNor)(phen)(NO(3))](+) for 5), nitrate counteranions, and lattice water molecules that provide crystalline stability through a network of hydrogen-bond interactions. The complexes exhibit a five coordinated motif in a square pyramidal environment around the metal center. The ability of compounds 4 and 5 to cleave DNA has also been studied. Mechanistic studies with different inhibiting reagents reveal that hydroxyl radicals, singlet oxygen, and superoxide radicals are all involved in the DNA scission process mediated by these compounds.     

New copper(I) phosphane complexes of dihydridobis(3-nitro-1,2,4-triazolyl)borate ligand showing cytotoxic activity

New copper(I) complexes of the type [H(2)B(tz(NO2))(2)]Cu[PR(3)](2) (1-5), [H(2)B (tz(NO2))(2)]Cu[dppe] (6) and [H(2)B(tz(NO2))(2)]Cu[PR(3)] (7, 8) have been synthesized from the reaction of CuCl, potassium dihydrobis(3-nitro-1,2,4-triazol-1-yl)borate, K[H(2)B (tz(NO2))(2)], and mono- or bi-dentate tertiary phosphanes. The complexes obtained have been characterized by elemental analyses and FT-IR in the solid state, and by NMR ((1)H and (31)P{(1)H}) spectroscopy in solution. Selected complexes 1, 3 and 5 have also been tested against a panel of several human tumor cell lines in order to evaluate their cytotoxic activity. Complexes 1 and 5 showed IC(50) values appreciably lower than those exhibited by cisplatin, the most used metal-based antitumor drug. It is worth noting that all three tested Cu(I) complexes appear to be particularly effective against A549 carcinoma cells that are resistant to cisplatin treatment.     

Palladium and platinum 3,5-diacetyl-1,2,4-triazol bis(thiosemicarbazones): chemistry, cytotoxic activity and structure-activity relationships

The preparation of platinum(II) complexes derived from 3,5-diacetyl-1,2,4-triazol bis(4-phenylthiosemicarbazone) (H(5)L(1)), 3,5-diacetyl-1,2,4-triazol bis(thiosemicarbazone) (H(7)L(2)), 3,5-diacetyl-1,2,4-triazol bis(4-methylthiosemicarbazone) (H(5)L(3)) and 3,5-diacetyl-1,2,4-triazol bis(4-ethylthiosemicarbazone) (H(5)L(3)) is described. The new complexes [Pt(mu-H(3)L(1))](2), [Pt(mu-H(5)L(2))](2), [Pt(mu-H(3)L(3))](2) and [Pt(mu-H(3)L(4))](2) have been characterized by elemental analyses, fast atom bombardment mass spectrometry (FAB(+)) and spectroscopic studies. The crystal and molecular structure of compounds [Pt(mu-H(3)L(1))](2), parent ligand H(5)L(1) and [Pt(mu-H(3)L(3))](2) have been determined by single crystal X-ray diffraction. The ligands coordinate, in a dideprotonate form to the platinum ions in a new tridentate fashion (NNS) and S-brigding bonding modes. Thus the molecular units of the platinum complexes are stacked as dimers. The testing of the cytotoxic activity of the synthesized compounds together with their palladium analogues against human A2780 and A2780cisR epithelial ovarian carcinoma cells lines suggests that the compounds may be endowed with important antitumor properties since they show IC(50) values in a micromolar range similar to those of cisplatin. The structure and antitumor activity relationships of platinum and palladium complexes are also discussed.     

Synthesis and biological evaluation of 4beta-[(4-substituted)-1,2,3-triazol-1-yl]podophyllotoxins as potential anticancer agents

A series of novel 4beta-[(4-substituted)-1,2,3-triazol-1-yl]podophyllotoxin derivatives were synthesized by employing Cu(I)-catalyzed click chemistry and evaluated for their anticancer activity against a panel of seven human cancer cell lines (HT-29, HCT-15, 502713, HOP-62, A-549, MCF-7, and SF-295). The compounds 9b, 9c, 9e, 9f, and 9h showed significant cytotoxic activities especially against HT-29, HCT-15, 502713 cell lines.     

Syntheses, crystal structures, and oxidative DNA cleavage of some Cu(II) complexes of 5-amino-3-pyridin-2-yl-1,2,4-triazole

Three new monomeric Cu(II) complexes of 5-amino-3-pyridin-2-yl-1,2,4-triazole (Hapt), [Cu(Hapt)(H(2)O)(2)(SO(4))] (1), [Cu(Hapt)(2)(H(2)O)(NO(3))](NO(3)) (2), and [Cu(Hapt)(2)(NCS-N)](NCS).H(2)O (3), have been prepared and characterized by single crystal X-ray diffraction. One distorted [CuN(2)O(2)+O(')] square-pyramidal (1), one distorted [CuN(3)O+N(')+O(')] octahedral (2), and one distorted [CuN(4)+N(')] intermediate between square-pyramidal and trigonal-bipyramidal (3) coordination configuration were found and are suggested to be due to the chelating nature of the ligand, which interacts with Cu(II) through the N4(triazole) and N(pyridine) atoms. Spectral properties of these chelates are in accordance with the X-ray structural data. With ascorbate and H(2)O(2) activation, compound 2 exhibits higher nuclease activity than compound 1. The influence on the DNA cleavage process of different scavengers of reactive oxygen species: dimethyl sulfoxide (DMSO), tert-butyl alcohol, sodium azide, 2,2,6,6-tetramethyl-4-piperidone and superoxide dismutase enzyme (SOD), and of the minor groove binder distamycin, is also studied.     

Synthesis and cytotoxic activities of novel copper and silver complexes of 1,3-diaryltriazene-substituted sulfonamides

In this study, a series of 10 novel copper (II) and silver complexes of 1,3-diaryltriazene-substituted sulfonamides was synthesised. All the synthesised ligands and their metal complexes were assessed for in vitro cytotoxicity against human colorectal adenocarcinoma (DLD-1), cervix carcinoma (HeLa), breast adenocarcinoma (MDA-MB-231), colon adenocarcinoma (HT-29), endometrial adenocarcinoma (ECC-1), prostate cancer (DU-145 and PC-3), normal embryonic kidney (HEK-293), normal prostate epithelium (PNT-1A), and normal retinal pigment epithelium (ARPE-19) cells. Most of the metal complexes from the series showed to be more active against all cancerous cells than the uncomplexed 1,3-diaryltriazene-substituted sulfonamides, and lower cytotoxic effects observed on normal cells. Most of the Cu (II) and Ag (I) metal complexes from the presented series showed high cytotoxic activity against HeLa cells with IC₅₀ values ranging from 2.08 to >300?µM. Specifically, compound L₃-Ag showed one of the highest cytotoxicity against all cancer cell lines with IC₅₀ values between 3.30 to 16.18?µM among other tested compounds.     

Synthesis, characterization, and antitumor activity of 5-iodouracil complexes.

Complexes of 5-iodouracil (5IU) with Mn(II), Co(II), Cu(II), Zn(II), and Cd(II) ions have been prepared, characterized, and subjected to a screening system for evaluation of antitumor activity against Sarcoma-180 (S-180) and L 929 tumor cells. The complexes were characterized by their elemental analysis, infrared spectra, electronic spectra, magnetic measurements, and powder x-ray diffraction. The antitumor activity results indicate that some complexes have good antitumor activity both in vivo and in vitro against S-180 and L 929 tumor cells.     

2-(3-Amino-3-deoxy-beta-D-xylofuranosyl)thiazole-4-carboxamide: a new tiazofurin analogue with potent antitumour activity

A new tiazofurin analogue, 2-(3-amino-3-deoxy-beta-d-xylofuranosyl)thiazole-4-carboxamide (3), was synthesized starting from d-glucose and evaluated for its in vitro antiproliferative activity against a panel of human tumour cell lines. Compound 3 exhibited the most powerful cytotoxicity against K562 cells, being approximately 100-fold more potent than tiazofurin. This analogue was also active against Jurkat, HT-29 and HeLa malignant cells, with respective IC(50) values being ca. 2-, 27- and 17-fold lower than those observed for tiazofurin. Remarkably, compound 3 did not exhibit any significant cytotoxicity towards normal foetal lung MRC-5 cell line.     

Molecular structure, bioavailability and bioactivity of [Cu(o-phen)2(cnge)](NO3)2.2H2O and [Cu(o-phen)(cnge)(H2O)(NO3)2] complexes

Two Cu(II) complexes with cyanoguanidine (cnge) and o-phenanthroline, [Cu(o-phen)(2)(cnge)](NO(3))(2).2H(2)O (1) and [Cu(o-phen)(cnge)(H(2)O)(NO(3))(2)] (2), have been synthesized using different experimental techniques and characterized by elemental analyses, FTIR, diffuse and UV-vis spectra and EPR and magnetic moment measurements techniques. The crystal structures of both complexes were solved by X-ray diffraction methods. Complex (1) crystallizes in the monoclinic space group C2/c with a=12.621(5), b=31.968(3), c=15.39(1)A, beta=111.68(4) degrees, and Z=8 and complex (2) in the monoclinic space group P2(1)/n with a=10.245(1), b=13.923(2), c=12.391(2)A, beta=98.07(1) degrees, and Z=4. The environments of the copper(II) center are trigonal bipyramidal (TBP) for [Cu(o-phen)(2)(cnge)](2+) and an elongated octahedron for [Cu(o-phen)(cnge)(H(2)O)(NO(3))(2)]. Solution studies have been performed to determine the species distribution. The superoxide dismutase (SOD) activities of both complexes have also been tested in order to determine if these compounds mimic the enzymatic action of the enzyme SOD that protects cells against peroxide radicals.     

Neuropharmacological actions of some binuclear lanthanide(III) complexes

Binuclear lanthanide(III) compounds are of great interest because of the potential of their mutual Ln(3+)-Ln(3+) electronic couplings to produce unusually sharp images in magnetic resonance and fluorescence imaging of biological tissue. The toxicity and neuropharmacological properties of the water soluble and stable neutral binuclear complex [La(api)](2) were compared with those of binuclear complexes with lower water stability, and the components used in their syntheses. The order of the 24-h LD(50) (mg/kg body wt.) of the compounds in mice was: salicylaldehyde (2.24)160). These compounds induced convulsions, urination and defecation in mice. Due to the relatively very low toxicity of [La(api)](2), its mode of action was explored. Its proconvulsant action may possibly involve an interaction of undissociated complex with muscarinic receptors, and is reversed by atropine.     

Design, synthesis and cytotoxic effect of hydroxy- and 3-alkylaminopropoxy-9,10-anthraquinone derivatives

In previous paper, we have reported the synthesis and the cytotoxic effect of 1,3-dihydroxy-9,10-anthraquinone derivatives. For further design of more potent compounds, a new series of 1-hydroxy-3-(3-alkylaminopropoxy)-9,10-anthraquinones and 3-(3-alkylaminopropoxy)-9,10-anthraquinones have been synthesized. The cytotoxicity of synthetic compounds were evaluated against human Hep G2, Hep 3B and HT-29 cells. Almost all compounds indicated significant inhibitory activity against Hep G2, Hep 3B and HT-29 cell lines in vitro. Compound 5 exhibited selective cytotoxicity against Hep G2 in a concentration-dependent manner with ED50 value of 1.23 +/- 0.05 microM. Structure-activity analysis revealed that most of the 1-hydroxy-3-(3-alkylamino-2-hydroxypropoxy)-9,10-anthraquinone showed stronger cytotoxic effects than those of 1-hydroxy-3- or 3-(3-alkylaminopropoxy)-9,10-anthraquinones against Hep 3B cell line in vitro. A sub-G1 cell stage and DNA fragmentation in MCF-7 cells were significantly observed after 72 h incubation with selective compound 16. The results show that 16 causes cell death by apoptosis.     

Inhibition of proinflammatory cytokine-induced invasiveness of HT-29 cells by chitosan oligosaccharide

The effect of chitosan oligosaccharide (COS, 1 kDa 相似文献   

Zinc complexes of benzothiazole-derived Schiff bases with antibacterial activity

Reaction of 2-acetamidobenzaldehyde with 2-amino-, 2-amino-4-methyl-, 2-amino-4-methoxy-, 2-amino-4-chloro-, 2-amino-6-nitro- and 2-amino-6-methylsufonylbenzothiazole afforded a series of Schiff bases. These compounds have been used for complexation reactions to obtain Zn(II) chelates having the same metal ion but different anions of the type [Zn(L)2]Xn [L = Schiff base derivative, X = SO4, NO3, C2O4 and CH3CO2 and n = 1 or 2] These complexes (Table I) have been characterized by physical, spectral, and analytical data. The Schiff bases act tridentately and their metal complexes were proposed to possess an octahedral geometry. To evaluate the antibacterial role of the anion, these compounds have been screened for antibacterial properties against pathogenic strains such as Escherichia coli, Staphylococcus aureus and Pseudomonas aeruginosa.     

Immunomodulatory cytokines suppress epithelial nitric oxide production in inflammatory bowel disease by acting on mononuclear cells

Inducible nitric oxide synthase (iNOS) activity in colonic epithelial HT-29 cells is modulated by the T-cell-derived cytokines IL-4 and IL-13, but is not affected by IL-10 despite its effect in models of colitis. We studied the effects of these cytokines on nitric oxide (NO) production by colonic tissue. IL-10 and IL-4 but not IL-13 suppressed the NO production and iNOS expression by inflamed tissue and cytokine-stimulated noninflamed tissue from patients with ulcerative colitis, whereas the three cytokines suppressed NO production in cytokine-stimulated biopsies from controls. To examine why colonic biopsies and HT-29 cells respond differently to immunomodulatory cytokines, a coculture of mixed mononuclear monocytes (MMC) and HT-29 cells was studied. Treatment of HT-29 cells with conditioned medium from IFN-γ/LPS-stimulated MMC produced significant amounts of NO, which suggested the presence of an MMC-derived soluble factor modifying epithelial NO production. Pretreatment of IFN-γ/LPS-stimulated MMC with IL-10 and IL-4 but not IL-13 suppressed NO production by HT-29 cells. Interestingly, pretreatment of HT-29 cells with IL-1 receptor antagonist suppressed the IFN-γ/LPS-stimulated MMC-induced NO production. These results suggest that immunomodulatory cytokines might exert an inhibitory effect on NO up-regulation by colonic epithelium via the inhibition of MMC-derived soluble mediators, such as IL-1.     

Synthesis, X-ray crystal structure, DNA binding, antioxidant and cytotoxicity studies of Ni(ii) and Pd(ii) thiosemicarbazone complexes

New complexes, [Ni(HL)(PPh(3))]Cl (1), [Pd(L)(PPh(3))](2), and [Pd(L)(AsPh(3))](3), were synthesized from the reactions of 4-chloro-5-methyl-salicylaldehyde thiosemicarbazone [H(2)L] with [NiCl(2)(PPh(3))(2)], [PdCl(2)(PPh(3))(2)] and [PdCl(2)(AsPh(3))(2)]. They were characterized by IR, electronic, (1)H-NMR spectral data. Further, the structures of the complexes have been determined by single crystal X-ray diffraction. While the thiosemicarbazone coordinated as binegative tridentate (ONS) in complexes 2 and 3, it is coordinated as mono negative tridentate (ONS) in 1. The interactions of the new complexes with calf thymus DNA was examined by absorption and emission spectra, and viscosity measurements. Moreover, the antioxidant properties of the new complexes have also been tested against DPPH radical in which complex 1 exhibited better activity than that of the other two complexes 2 and 3. The in vitro cytotoxicity of complexes 1-3 against A549 and HepG2 cell lines was assayed, and the new complexes exhibited higher cytotoxic activity with lower IC(50) values indicating their efficiency in killing the cancer cells even at very low concentrations.     

Design of copper DNA intercalators with leishmanicidal activity

The complexes [Cu(dppz)(NO(3))]NO(3) (1), [Cu(dppz)(2)(NO(3))]NO(3) (2), [Cu(dpq)(NO(3))]NO(3) (3), and [Cu(dpq)(2)(NO(3))]NO(3) (4) were synthesized and characterized by elemental analysis, FAB-mass spectrometry, EPR, UV, and IR spectroscopies, and molar conductivity. DNA interaction studies showed that intercalation is an important way of interacting with DNA for these complexes. The biological activity of these copper complexes was evaluated on Leishmania braziliensis promastigotes, and the results showed leishmanicidal activity. Preliminary ultrastructural studies with the most active complex (2) at 1 h revealed parasite swelling and binucleated cells. This finding suggests that the leishmanicidal activity of the copper complexes could be associated with their interaction with the parasitic DNA.     

Synthesis and cytotoxicity evaluation of 2-amino- and 2-hidroxy-3-ethoxycarbonyl-N-substituted-benzo[f]indole-4,9-dione derivatives

Reaction between 2,3-dichloronaphthoquinone (I) and ethyl cyanoacetate or diethyl malonate under different conditions gave the starting materials, 2-chloro-3-(alpha-cyano-alpha-ethoxycarbonyl-methyl)-1,4-naphthoquinone (A) or 2-chloro-3-(diethoxycarbonyl-methyl)-1,4-naphthoquinone (B). The 2-amino-3-ethoxycarbonyl-N-substituted-benzo[f]indole-4,9-dione derivatives [A-(1-10)] and 2-hydroxy-3-ethoxycarbonyl-N-substituted-benzo[f]indole-4,9-dione derivatives [B-(1-12)] were prepared from compounds A and B, respectively, by using various alkyl-, and arylamines. The cytotoxic activities of the prepared compounds were evaluated by SRB (Sulforhodamine B) assay against the following tumor cell lines: A459 (human lung), SK-OV-3 (human ovarian), SK-MEL-2 (human melanoma), XF498 (human CNS), and HCT 15 (human colon). Many of the derivatives mentioned exhibited more potent cytotoxic effects against SK-OV-3 and XF498 than etoposide. Significantly, 2-amino-3-ethoxycarbonyl-N-(3-methyl-phenyl)-benzo[f]indole-4,9-dione (A-8) showed potent activity against all tumor cell lines, and in particular, its cytotoxic effect against SK-OV-3 was much higher than doxorubicin.     

Bioactivity-guided isolation of cytotoxic constituents from stem–bark of Premna tomentosa

A bioassay-guided fractionation and chemical investigation of the stem bark of Premna tomentosa resulted in the isolation and characterization of four new icetexane diterpenes (1–4), along with the known compounds coniferaldehyde (5), syringaldehyde (6), lupeol (7), betulin (8), and 2-(4-methoxyphenyl)-2-butanone (9). Their structures were established on the basis of extensive spectroscopic (IR, MS, 2D NMR) data analysis and by comparison with the spectroscopic data reported in the literature. The new compounds exhibited diverse functionalities on a common icetexane diterpene skeleton. In addition, cytotoxic activities of the icetexanes (1–3) were evaluated by determining their inhibitory effects on the human cancer cell lines (MCF-7, HT-29, Hep-G2, A-431, and A-549). Compounds 1 and 3 showed selective inhibitory activity against MCF-7 (15.96 μg/mL and 15.84 μg/mL) and HT-29 cell lines (16.21 μg/mL and 14.57 μg/mL), respectively.