Synthesis and antitumor activity of a new mixed-ligand complex di-n-butyl-(4-chlorobenzohydroxamato)tin(IV) chloride

Reaction of di-n-butyltin(IV) dichloride with 4-chlorobenzohydroxamic acid at 1:1 ratio yielded a new mixed-ligand diorganotin(IV) complex, di-n-butyl-(4-chlorobenzohydroxamato)tin(IV) chloride(DBDCT). It was fully characterized by IR, ¹H, ¹³C, ¹¹⁹Sn NMR spectra and single crystal X-ray analysis. In DBDCT, the tin atom is five-coordinated in a trigonal bipyramidal geometry. DBDCT exhibited strong in vitro cytotoxic activity toward human immature granulocyte leukemia (HL-60), human salivary-gland carcinoma (SGC-7901), human henrietta carcinoma (Hela) and human urinary bladder (T24) cell lines which, in some cases, were equal to, or even higher than those of cis-dichlorodiammineplatinum(II) (cisplatin, DDP), the widely clinically used drug. The further in vivo antitumor tests of DBDCT towards the transplantation tumor models of sarcoma carcinoma (S₁₈₀), hepatocellular carcinoma (H₂₂) and Ehrlich’s ascites carcinoma (EAC) on mice were carried out via injection intraperitoneally with cisplatin as positive contrast drug. The results showed that DBDCT displayed in vivo antitumor activity against the hepatocellular carcinoma H₂₂ and sarcoma carcinoma S₁₈₀ which were close to those of cisplatin, meanwhile, the survival-extending rates at middle dose and high dose on mice Ehrlich’s ascites tumor EAC were higher than those of cisplatin, and there was a good dose-effect relationship.     

In vivo antitumour activity of amphiphilic silicon(IV) phthalocyanine with axially ligated rhodamine B

We explore the possible cellular cytotoxic activity of an amphiphilic silicon(IV) phthalocyanine with axially ligated rhodamine B under ambient light experimental environment as well as its in vivo antitumour potential using Hep3B hepatoma cell model. After loading into the Hep3B hepatoma cells, induction of cellular cytotoxicity and cell cycle arrest were detected. Strong growth inhibition of tumour xenograft together with significant tumour necrosis and limited toxicological effects exerted on the nude mice could be identified.     

Spectroscopic and magnetic properties of a Ni(II) complex with citric acid

The complex compound K₂[Ni(cit)(H₂O)₂]₂·4H₂O (cit = triionized citrate ion) seems to be a good model for the investigation of Ni(II)/citrate interactions that are of interest in relation to nickel metabolism and bioaccumulation. Its infrared and Raman spectra were recorded and analyzed on the basis of its structural peculiarities. The magnetic susceptibility, investigated in the temperature range between 1.9 and 300 K, shows the absence of magnetic interactions between the two metal centers present in this structure.     

Synthesis,reactions, spectral and magnetic studies of bimetallic alkoxides of cobalt(II) with zirconium(IV)

A bimetallic isopropoxide of cobalt(II) with the formula Co[Zr₂(OPrⁱ)₉]₂, prepared by the reaction of COCl₂ with K[Zr₂(OPrⁱ)₉] in 1:2 molar ratio, has been shown to undergo alcoholysis reactions with graded alcohols (primary, secondary and tertiary) to afford products of the types, Co[Zr₂(OR)₉]₂ (where R = Me, Et, Prⁿ, Buⁿ, Buⁱ and Bu^s) Co[Zr₂(OPrⁱ)₃(OEt)₆]₂, Co[Zr₂(OPrⁱ)₆(OBu^s)₃]₂, CO[Zr₂(OPrⁱ)₃(OBu^s)₆]₂, Co[Zr₂(OPrⁱ)₆(OBu^t)₃]² and Co[Zr₂(OPrⁱ)₃(OR)₆]₂ (where R = Am^t or Bu^t). These derivatives have been characterized by elemental analyses and molecular weight determinations. Infrared, electronic (visible) spectral and magnetic susceptibility measurements suggest a distorted octahedral geometry for these derivatives.     

Synthesis, characterization, crystal structure and antitumor activity of organotin(IV) compounds bearing ferrocenecarboxylic acid

Four new organotin(IV) complexes [(Bu₃Sn)(FcCOO)]_n (1), [(μ-Bu₂Sn)₂(μ-Bu₂SnFcCOO)₂(μ₃-O)₂(μ-OCH₃)₂]₂ (2), [Ph₃Sn(FcCOO)(H₂O)](phen) (3) and [{Ph₃Sn(FcCOO)}₂(4,4′-bipy)] (4) [Fc = (η⁵-C₅H₅)Fe(η⁵-C₅H₄)] have been synthesized and characterized by elemental analyses, IR, (¹H and ¹³C) NMR spectra and X-ray single-crystal diffraction analyses. The structure analyses show that all tin atoms in complexes 1-4 are five-coordinated with trigonal bipyramid geometry. Complexes 1-4 and FcCOOH undergo reversible one-electron oxidations in methanol solution. The antitumor activities of complexes 1-4 have also been tested. Complexes 1 and 2 exhibit medium activity towards P388 cell lines and Hela cell lines. Complexes 3 and 4 exhibit medium activity towards P388 cell lines but strong activity towards Hela cell lines. This may result from complexes 3 and 4 including the neutral molecules 1,10-phenanthroline and 4,4′-bipy.     

Synthesis and characterization of pure cubic zirconium oxide nanocrystals by decomposition of bis-aqua, tris-acetylacetonato zirconium(IV) nitrate as new precursor complex

Pure zirconium oxide (ZrO₂) nanocrystals with diameters 10-30 nm are fabricated from bis-aqua, tris-acetylacetonato zirconium(IV) nitrate; [Zr(acac)₃(H₂O)₂](NO₃); by thermal decomposition. The different combinations of oleylamine, or polyethyleneglycol (PEG) and triphenylphosphine, were added as surfactants to control the particle size. The products were characterized by X-ray diffraction (XRD), transmission electron microscopy (TEM), ultraviolet-visible (UV-Vis) spectroscopy, photoluminescence spectroscopy (PL), Fourier transform infrared (FT-IR) spectroscopy and X-ray photoelectron spectroscopy (XPS) to depict the phase and morphology. The synthesized ZrO₂ nanoparticles have a cubic structure. The FT-IR spectrum showed the purity of obtained ZrO₂ nanocrystals with cubic phase. The UV-Visible absorption peak for ZrO₂ was observed at 233 nm (5.3 eV in photon energy). The band at 363 nm for cubic ZrO₂ nanocrystals was found.     

Synthesis,characterization and antitumor activity of novel octahedral Pt(IV) complexes

Novel platinum(IV) complexes were synthesized having octahedral structure for new antitumor agents. The series of (1,4-butanediamine)Pt(IV) complexes of the type trans,cis-[PtA(2)Cl(2)(1,4-butanediamine)] (A=hydroxo 9, acetato 12, trifluoroacetato 13 as axial ligands) and trans-[PtA(2)(malonate)(1,4-butanediamine)] (A=hydroxo 16, acetato 17, trifluoroacetato 18) were synthesized and characterized by IR, NMR and elemental analysis. The molecular structures of 12, 13 and 18 have been determined by X-ray diffraction methods. The crystals are monoclinic, P2 1/c with a=21.165 (5), b=9.050 (3), c=15.293 (3) A, beta=103.89 (2) degrees and Z=8 for 12, a=10.178 (5), b=12.894 (9), c=12.182 (8) A, beta=91.01 (5) degrees and Z=4 for 13 and a=10.460 (5), b=11.199 (8), c=15.641 (7) A, beta=98.41 (5) degrees, Z=4 for 18. Three crystallographically independent molecules of 12, 13 and 18 have octahedral coordination around Pt(IV) cation. The trans,cis-[PtA(2)Cl(2)(1,4-butanediamine)] were prepared by acetylation or trifluoroacetylation of trans,cis-[Pt(OH)(2)Cl(2)(1,4-butanediamine)]. The trans-[PtA(2)malonate(1,4-butanediamine)] 17 and 18 was prepared by a similar method. The in vitro cytotoxicity of theses Pt(IV) complexes have been evaluated against 12 cancer cell lines assayed by MTS method. The IC(50) values of the compounds 12 and 13 were shown to be lower than those of cisplatin. The in vivo antitumor activity of the Pt(IV) complexes was evaluated using mice bearing L1210 leukemia, B16 melanoma and L1210/cis-DDP cancer animal models. The compound 18 was found to highest activity against cisplatin-resistant cancer cells, L1210/cis-DDP, in vivo.     

Synthesis and properties of new substituted 1,2,4-triazoles: potential antitumor agents

Cycloaddition of the reactive intermediates 4 with 1-(cyanomethyl)benzotriazole (5) and its N-2 isomer 9 furnished, after spontaneous rearrangements, the 1,2,4-triazole derivatives 8 and 10. Analogously, reaction of 4 with ethyl cyanoacetate lead to the 1,3,5-trisubstituted 1,2,4-triazoles 12, which gave on treatment with hydrazine the corresponding hydrazides 13. Treatment of 13d with galactose or phenyl isothiocayanate gave the 1-D-galactose-acylhydrazone 14 and the 1,2,4-triazole derivative 15, respectively. Compounds 8c; 10b,c; 13a,c and 14 were selected for the antitumor screening, whereby 8c, 13a, and 13c showed remarkable activity against leukemia, ovarian, renal and lung cancers (8c with Gl(50) of 0.70 microM, 0.07 microM against leukemia (CCRF-CEM and RPMI-8226), 0.02 microM against ovarian (OVCAR-3) and 0.60 microM against renal (CARKI-1) and lung cancers, respectively).     

On the synthesis, cytostatic and antitumor properties of new Pt(II) and Pt(IV) complexes with chloroanilines

The paper reports the synthesis, the chemical characterization and the IR data of new Pt(II) and Pt(IV) complexes, as well as their cytostatic activities on KB cells and antitumour properties against three tumour systems (P388 and L1210 leukemias and advanced B16 melanoma). The following ligands were used: 2,5-dichloroaniline, 3,4-dichloroaniline, 2,4,6-trichloroaniline, 3,4,5-trichloroaniline, 2,3,4,5-tetrachloroaniline and 2,3,5,6-tetrachloroaniline. The tri- and tetrachloroaniline-Pt(II) complexes displayed a fairly good antileukemic activity but lower than cisplatin. The effect of these compounds against advanced B16 melanoma appears more interesting. They show an activity comparable or in some cases higher than cisplatin and other 1,2-diaminocyclohexane-Pt(II) complexes. The M.O. Huckel's calculations were performed on the ligand molecules in order to help us to draw a structure-activity relationship for new compounds.     

The reactions of zirconium(IV) bromide and zirconium(III) bromide and chloride with ammonia and zirconium(IV) bromide with ammonium cyanide

Unlike ZrCl₄, ZrBr₄ is not ammonolysed in liquid ammonia at temperatures up to −33 °C. The existence of ammoniates ZrBr₄nH₃ (n = 17, 12 and 9) at −36 °C has been established; at room temperature, the hexammine ZrBr₄ · 6NH₃ is the stable species which becomes ZrBr₄ · 2NH₃ at 200 °C. When treated with an excess of NH₄CN in liquid ammonia, complete replacement of bromide ions by cyanide occurs to give an inseparable mixture of Zr(CN)₄ · 2NH₃ and NH₄Br. The chloride and bromide of zirconium(III) also undergo no ammonolysis in liquid ammonia; the ammoniates stable at room temperature are ZrCl₃ · 2.5NH₃ and ZrBr₃ · 6NH₃.     

Synthesis and anthelmintic activity of substituted (R)-phenyllactic acid containing cyclohexadepsipeptides

The substituted (R)-phenyllactic acid containing cyclohexadepsipeptides (CHDPs) represent novel enniatin derivatives with strong in vivo activities against the parasitic nematode Haemonchus contortus Rudolphi in sheep. 2D NMR spectroscopic analysis revealed for the substituted (R)-phenyllactic acid containing CHDPs one major conformer with an unsymmetrically folded conformation lacking a cis-amide bond. A correlation between the substitution pattern and its anthelmintic activity was found. Here we report on a simple total synthetic pathway of the precursor for this particular type of CHDPs and an efficient modification of the benzylic side chain (R-PhLac(2)).     

Synthesis, characterization and in vitro antitumor activity of three organotin(IV) complexes with carbazole ligand

Three novel organotin(IV) complexes with 2-(9H-carbazol-9-yl) acetic acid (HL), of the formulae {[nBu₂SnOL]₂O}₂ (1), [nBuSn(O)OL]₆ (2) and [nBu₃SnOL]₆ (3) were prepared. All compounds were characterized by X-ray crystallography, confirming that complex (1) is tetranuclear one with ladder framework, complex (2) is a hexanuclear organotin(IV) complex with drum structure and complex (3) is a macrocycle with 24-membered stannoxane ring. Furthermore, all complexes were tested in vitro for their cytotoxic activity, using human hepatocellular carcinoma cell line (BEL-7402) and human hepatocellular liver carcinoma cell line (HepG2). Complex (1) displayed the best cytotoxicity and can be pointed out as a promising substrate to be subject of further investigations.     

Synthesis, characterization and antitumor activity of copper(II) complex with nicotinamido-4-bis(2-chloroethyl)aminobenzaldimine.

Nicotinamido-4-bis(2-chloroethyl)aminobenzaldimine (NBAB) was synthesized and characterized by elemental analysis, IR and 1H NMR spectra. The complex of Cu(NBAB)2(NO3)2 was prepared in ethanol and characterized by elemental analysis, conductivity, cyclic voltammetry, IR, UV-Vis, fluorescence, CD and EPR spectra. The characteristic data suggest that the complex has an elongated octahedral structure, and NBAB behaves as bidentate in the keto form. The antitumor activities of NBAB and the complex against L1210 murine leukemia and K562 were investigated with both the MTT method and the colony formation test. The results in vitro indicate that antitumor activities of NBAB are superior to 2,2'-chlorodiethylamine hydrochloride (nitrogen mustard) for L1210, and inferior to nitrogen mustard for K562, but the antitumor activities of the complex for both cell lines are superior to nitrogen mustard.     

Synthesis and antitumor activity of selected 7-alkylidene substituted cephems

Selected 7-alkylidene substituted cephems were synthesized and subjected to antitumor assay. The effect of substituents was examined to establish structure-activity relationships. It was found that the intensive intracellular generation of nitric oxide induced by tert-butyl 7-alkylidene cephalosporanate sulfones could be also regarded as an additional cytotoxic factor taking place both in vitro and in vivo experiments.     

Synthesis, cytotoxicity and antitumor activity of platinum(II) complexes of cyclopentanecarboxylic acid hydrazide

New platinum(II) complexes of cyclopentanecarboxylic acid hydrazide (cpcah) were prepared, characterized by elemental analysis, IR and 1H NMR spectra, and evaluated for in vitro cytotoxicity in Friend leukemia (FL) and A2780 ovarian tumor cells, induction of apoptosis in FL cells, as well as for in vivo antitumor activity toward murine L1210 leukemia and Lewis lung carcinoma. The spectral analyses indicated a cis-square planar structure of the complexes with hydrazide ligand coordinated via the NH2 group. The compounds exerted significantly lower in vitro and in vivo toxicities as compared with those of cisplatin (cis-diamminedichloroplatinum(II), DDP). On the other hand, the complex [Pt(NH3)(cpcah)Cl2] exhibited antitumor activity against L1210 leukemia in mice comparable to that of cisplatin, resulting at a dose of 42 mg/kg (administered 3 times) in a T/C (mean survival time) of 280%. This compound displayed an in vitro macromolecular synthesis inhibition pattern similar to that of DDP. At concentrations close to the cytostatic ones (10-20 microM) this complex, as well as DDP, was able to induce apoptosis in FL cells as shown by neutral comet assay and morphological analysis. We concluded that there is a correlation between the ability of platinum complexes to induce apoptosis and their antitumor activity.     

Synthesis, characterization and crystal structure of manganese (IV) complex derived from salicylic acid

The binuclear manganese (IV) [Mn₂(Hsal)₄(OH)₄] (H₂sal = salicylic acid) complex has been obtained from a complex reaction mixture in methanol consisting of Mn(II)(OAc)₂ · 4H₂O, GS ( a reagent obtained by refluxing glycine and salicylaldehyde in 1:1 molar ratio in methanol), monosodium salicylate and pyridine. The compound contains a distorted octahedral MnO₆ coordination unit of potential importance to high oxidation state manganese bimolecules.     

Synthesis and antibacterial activity of new fluoroquinolones containing a substituted N-(phenethyl)piperazine moiety

N-(Phenethyl)piperazinyl quinolone derivatives that bear a methoxyimino-substituent have been synthesized and evaluated for antimicrobial activity against Gram-positive and Gram-negative microorganisms. In addition, to define structure-activity relationships, ciprofloxacin derivatives containing 2-oxo-2-phenylethyl or 2-hydroxyimino-2-phenylethyl moieties at N-4 position of piperazine ring were prepared and tested. Ciprofloxacin derivatives, containing a N-(chloro-substituted phenethyl) residue, showed in vitro Gram-positive and Gram-negative activity generally comparable or superior to that of reference quinolones.     

X-ray structure, solution properties, and biological activity profile of vanadocene(IV) acetylacetonate complex,

The structure of [V(eta5-C5H5)2(CH3C(O)CHC(O)CH3)](O3SCF3) (1) (=[VCp2(acac)](O3SCF3)), a dual-function anti-cancer agent with anti-angiogenic and anti-mitotic properties, was determined by single-crystal X-ray diffraction. The geometry is well described as a pseudo-tetrahedral like structure with the centroids of the cyclopentadienyl rings and the two oxygen atoms of the acetylacetonate ring in the ancillary positions of the central vanadium (IV) atom. The bisector of the V(acac) fragment deviates from the C2 axis of the ligand framework by only 4 degrees, compared to a deviation of 7 degrees for the V(acac) fragment in the tetramethylethano-bridged vanadocene acetyl acetonate complex. Crystal data for 1: space group, P2(1)/c; a=7.5544(9) A, b=14.936(2) A, c=16.193(2) A, beta=102.901(2) degrees, V= 1781.0(4) A3; Z=4; R=0.0506 for 2310 reflections with I> 2sigma(I). This report also details the electron paramagnetic resonance, UV/Vis spectroscopy, electrochemical properties and the biological activity profile of this potent anti-cancer agent.     

Synthesis,antitumor activity and DNA binding features of benzothiazolyl and benzimidazolyl substituted isoindolines

In this paper novel isoindolines substituted with cyano and amidino benzimidazoles and benzothiazoles were synthesized as new potential anti-cancer agents. The new structures were evaluated for antiproliferative activity, cell cycle changes, cell death, as well as DNA binding and topoisomerase inhibition properties on selected compounds. Results showed that all tested compounds exerted antitumor activity, especially amidinobenzothiazole and amidinobenzimidazole substituted isoindolin-1-ones and benzimidazole substituted 1-iminoisoindoline that showed antiproliferative effect in the submicromolar range. Moreover, the DNA-binding properties of selected compounds were evaluated by biophysical and biochemical approaches including thermal denaturation studies, circular dichroism spectra analyses and topoisomerase I/II inhibition assays and results identified some of them as strong DNA ligands, harboring or not additional topoisomerase II inhibition and able to locate in the nucleus as determined by fluorescence microscopy. In conclusion, we evidenced novel cyano- and amidino-substituted isoindolines coupled with benzimidazoles and benzothiazoles as topoisomerase inhibitors and/or DNA binding compounds with potent antitumor activities.