The mono- and bis-(trichloroacetic acid)-solvates of ferricenium trichloroacetate

Summary Inconsistent literature reports on the preparation of the mono- and bis-(trichloroacetic acid)-solvated ferricenium trichloroacetates, (1) and (2) have prompted a comprehensive investigation of the experimental conditions giving rise to the formation of the two ferricenium salts. In agreement with the majority of authors, (2) is reproducibly obtained from trichloroacetic acid and ferrocene in molar ratios of 3 and higher in benzene over a wide range of experimental variables in the presence of air or, preferably, under conditions of oxygen saturation. Treatment of aqueous ferricenium sulfate solutions with trichloroacetic acid in an acid/ferrocene ratio of 3 and above affords the di-solvate, whereas at lower reactant ratios, and under conditions of reduced acidity, formation of the mono-solvate prevails. More efficiently, and in a higher degree of purity, the latter salt is generated from the former by a controlled recrystallization from water. Representative spectroscopic features of the two salts are discussed.     

Antitumor effects of binuclear ferrocene derivatives

On the basis of an earlier model of chemical carcinogenesis, the antitumor activity of the mono-, bi- and poly-nuclear ferrocene derivatives ferricenium tri-iodide (1), ferricenium tetrachloroferrate (2), 1, 1′-diethylferricenium triiodide: (3), N-(ferrocenylmethyl)hexamethylenetetramine tetrafluoroborate (4), bis(ferrocenylmethyl)benzotriazolium tetrafluoroborate (5), bis(ferrocenyl-α-ethyl)benzotriazolium tetrafluoroborate (6) and bis(ferrocenylmethyl)-2-methylbenzimidazolium tetrafluoroborate (7), and the oligomer (—Fc—CH₂—Fc^+˙—CH₂—)_7–8^? (PF₆)_7–8 (8) was studied in vivo (Fc?C₁₀H₈Fe). The tumor models studied included MCH-11 (mouse sarcoma induced by methylcholantrene), P-815 (mouse mastocytoma of DBA/2 origin) and virus-induced Raucher leukemia (RLV). The cytotoxic effects of these preparations were examined against in vitro cultured normal murine cells (line L-929). The binuclear ferrocene derivatives 5, 6 and 7 inhibited the development of experimental tumors in mice. Ferricenium tri-iodide (1) was effective in Rauscher leukemia. Kinetic dependencies for most complexes had a two-phase character: the region of inhibition of tumorogenesis was followed by a region in which the complexes accelerated the development of this process. The link between the structure of compounds 1–8 and their antitumor effects is discussed.     

Two New Eremophilane‐Type Sesquiterpenoids from the Rhizomes of Ligularia veitchiana (Hemsl.) Greenm

Two new eremophilane‐type sesquiterpenoids eremophil‐6‐en‐11‐ol ( 1 ) and (7α,9α,10α)‐9,10‐epoxy‐eremophilan‐11‐ol ( 2 ), together with a known eremophilane‐type (6α,8α)‐6,8‐dihydroxyeremophil‐7(11)‐en‐12‐oic acid 12,8‐lactone ( 3 ) were isolated from the rhizomes of Ligularia veitchiana. The structures of 1 and 2 were established by spectral analysis including ¹H‐ and ¹³C‐NMR, HSQC, HMBC, and HR‐ESI‐MS data. The compounds 1 and 3 were assessed against lung‐cancer (A549) and stomach‐cancer (BCG823) cell lines by the MTT method. The results showed that 1 exhibited significant inhibiting activities on the growth of these cancer cells with IC₅₀ values between 1–100 μg/ml, whereas compound 3 had no effect on the same cell lines.     

Synthesis and anticancer activity of benzotriazole derivatives

A series of benzotriazole (BTA) derivatives were synthesized as tyrosine protein kinase inhibitors using fragment-based design strategy. All desired compounds were synthesized with the reaction of benzotriazole, chloroacetonitrile and aromatic aldehyde using Ultrasonic-Microwave method and characterized by IR, ¹H and ¹³C-NMR, mass spectrometry (MS) and elemental analysis. The anticancer activity of these compounds was evaluated by CCK-8 method against carcinoma VX2, lung cancer A549, stomach cancer cell lines MKN45 and MGC in vitro. The results showed that all compounds showed good antiproliferative activity. In particular, compound 2.1 showed the most prominent inhibition of VX2 cell lines with IC₅₀ of 3.80 ± 0.75 μM. Compound 2.2 exhibited highly potent anticancer activity of stomach MGC cell lines with IC₅₀ of 3.72 ± 0.11 μM. A549 and MKN45 cell lines were sensitive to compound 2.5 with IC₅₀ of 5.47 ± 1.11 and 3.04 ± 0.02 μM, respectively.     

Synthesis and Biological Activity of Some New Pyrazole Copper(II) Complexes

As a part of systematic investigation of synthesis and biologically active compounds of pyrazole derivatives containing transition metal, several new pyrazole copper(II) complexes 3a?f were synthesized from pyrazole sodium salts 2a?f , which were produced from spiro‐pyrazoles 1a?f and sodium hydride by a ring‐opening reaction. All the synthesized compounds were characterized by spectroscopic analysis. Pyrazole copper(II) complexes 3a?d and 3f exhibited high DNA cleavage activity in vitro. Furthermore, compounds 3a?f were tested for their growth inhibitory activity in A549 lung cancer, B16F10 murine melanoma, and HeLa human uterine carcinoma cells. Compounds 3c,d displayed moderate B16F10 and HeLa inhibitory activity levels ( 3c : IC₅₀ = 45 μM in B16F10 cells and 34 μM in HeLa cells, 3d : IC₅₀ = 50 μM in B16F10 cells and 32 μM in HeLa cells).     

Antineoplastic activity of polyaspartamide–ferrocene conjugates

The ferrocene/ferricenium redox system plays a significant role in biological oxidation, reduction and free-radical reactions. Of particular interest are the findings of earlier investigations which showed certain water-soluble ferricenium salts to possess appreciable antiproliferative activity against various murine tumor lines and a xenografted human colorectal adenocarcinoma. Solubility in water, a prerequisite for efficacious transport and dissipation in central circulation, was then proposed as a principal requirement for the ferrocene complex system to exert antineoplastic activity irrespective of the oxidation state in which it is administered. In order to shed more light on this question, we decided to investigate the antiproliferative properties of polymer–ferrocene conjugates containing the metal complex in the non-oxidized (ferrocene) form while fulfilling the critical requirement of water solubility. To this end, five selected, water-soluble conjugates, synthesized by reversible coupling of 4-ferrocenylbutanoic acid to variously structured polyaspartamides featuring pendant primary amino groups as coupling sites, were tested in vitro against cultured HeLa cells at concentrations up to 50 µg Fe ml⁻¹. Optimal antiproliferative activities, with IC₅₀ in the range of 2–7 µg Fe ml⁻¹, were determined for three compounds possessing tertiary-amine functions susceptible to protonation at physiological pH. Lower activities (IC₅₀ = 45–60 µg Fe ml⁻¹) were demonstrated for two poly(ethylene oxide)-containing conjugates. However, no reasonable structure–performance relationships can be derived at this stage from the small number of compounds tested. Copyright © 1998 John Wiley & Sons, Ltd.     

Synthesis and NMR Spectroscopic Characteristics of a Series of Hydrazide‐Hydrazones Containing Furoxan Ring Derived from Isoeugenoxyacetic Acid

A novel hydrazide, 2‐methoxy‐4‐(3‐methyfuroxan‐4‐yl)‐5‐nitrophenoxyacetylhydrazine, was prepared from isoeugenoxyacetic acid. The hydrazide was condensed with aromatic aldehydes to give a series of 20 hydrazide‐hydrazones incorporating the furoxan ring. The structure of obtained compounds was determined by analytical and spectral data. It was demonstrated that the two sets of resonance signals in the ¹H‐NMR and ¹³C‐NMR spectra of the examined hydrazide‐hydrazones are caused by E_N–C(O) and Z_N–C(O) conformers. The energy barriers for the conformation exchange were determined by ¹H‐NMR‐measurement at various temperatures. Among seven tested hydrazide‐hydrazones, four compounds exhibit inhibition activities in vitro on human epidermis carcinoma (KB‐cell) with IC₅₀ = 47, 68, 79, and 103 μg/mL.     

Diterpenoids from the Hainan Soft Coral Sinularia parva

Two new cembrane diterpenes, sinulaparvalides A and B ( 1 and 2 , resp.), which contain an intriguing seven‐membered lactone moiety, along with the four known related cembranoids 3 – 6 , were isolated from the Hainan soft coral Sinularia parva. The structures of compounds 1 and 2 were established by spectroscopic methods, mainly on the basis of 2D‐NMR techniques, and were confirmed by single‐crystal X‐ray diffraction analysis. The in vitro cytotoxic activities of these compounds were tested on human colon carcinoma (HCT‐116), human promyelocytic leukemia (HL‐60), and human lung carcinoma (A‐549) tumor cell lines.     

Novel Bis(1,2,4-oxadiazolyl) Fused Thiazole Derivatives: Synthesis and Anticancer Activity

A novel series of bis-1,2,4-oxadiazole fused benzothiazole derivatives 9a–9j are synthesized, and their structures are confirmed by ¹H and ¹³C NMR, and mass spectral data. All products are evaluated in vitro for their anticancer potential against a panel of four human cancer cell lines such as lung cancer (A549), breast carcinoma (MCF-7), melanoma (A375), and colon cancer (HT-29). The combretastatin-A4 is used as standard drug. All compounds 9a–9j exhibit significant anticancer activity with IC₅₀ values ranging from 0.11±0.01 to 14.6±3.89 μM. Among these, compounds 9a–9d, 9h, 9i demonstrate more potent activity than the control.

     

Efficacy of selected triorganotin(IV) compounds on leaves against Phytophthora palmivora (Butler) Butler isolated from black pepper and cocoa

Several triorganotin(IV) compounds and Terrazole® 35 WP were screened for their in vitro antifungal activity against three isolates of Phytophthora palmivora. Two isolates (isolates Phy. 2 and Phy. 334) were obtained from black pepper (Piper nigrum L.) and one isolate (isolate Phy. 56) from cocoa leaves (Cacao theobromae). ED₅₀ values for radial growth of the isolates ranged from 0.09 to 1,700 μg cm^?3 for the triorganotin(IV) compounds and from 3.46 to 1 227 000 μg cm^?3 for Terrazole®. Diphenylbutyltin bromide exhibited the highest antifungal activity against the three isolates of P. palmivora with ED₅₀ values ranging from 0.30 to 0.73 μg cm^?3. Diphenylbutyltin bromide was equally effective against a freshly isolated virulent culture of P. palmivora (isolate Phy. 346) from black pepper leaves in Sarawak, East Malaysia, yielding an ED₅₀ value for radial growth of 0.87 μg cm^?3 and a probit-log concentration regression line slope value of 1.04. In vitro efficacy of diphenylbutyltin bromide against isolate Phy. 346 using detached healthy pepper leaves showed 40–75% infection of leaves at 100 μg cm^?3 and no infection at 500 μg cm^?3. Diphenylbutyltin bromide at 100 μg cm^?3, however, inhibited the diameter of lesion by 43.3–73.7% compared with the untreated controls. Black pepper leaves treated with Terrazole® at 778 μg cm^?3 exhibited 5.3–33.3% inhibition of lesion diameter compared with the untreated controls, where 90–100% of the leaves were infected. Concentrations of diphenylbutyltin bromide of 1000–2500 μg cm^?3 caused some injury lesions on the leaves. From the results obtained, it appears that diphenylbutyltin bromide could be used as a protective spray or drench against P. palmivora infection of black pepper at 100–500 μg cm^?3.     

Synthesis and Urease Inhibition Studies of Barbituric and Thiobarbituric Acid Derived Sulphonamides

Various novel barbituric and thiobarbituric acid derived sulphonamides were synthesized in excellent yield via three components single pot reaction; and these were screened for in vitro urease inhibition studies against jack bean urease. The compounds 1‐7 were found to exhibit a low to moderate activity whereas compounds 8‐14 showed a significant activity (88.3‐99.9% inhibition determined at 500 μM concentration). Structures of the synthesized compounds were confirmed by ¹H‐NMR, ¹³C‐NMR, mass spectrometry and elemental analysis data.     

Synthesis and Characterization of New Binaphthyl‐Linked Phenanthroline‐, Bipyridine‐, or Pyridine‐Derived Ligands,and the Study of Their Cytotoxic Activity

In the present work, we describe the synthesis and characterization of five new versatile acyclic or macrocyclic ligands containing binaphthyl‐linked pyridine, bipyridine, or phenanthroline groups in their framework (see Schemes 1–4). The structures of the ligands were elucidated on the basis of elemental analyses, IR, ¹H‐NMR, ¹³C‐NMR, and FAB mass spectra. The cytotoxicity of these compounds was tested in vitro by using the tetrazolium salt reduction (MTT) assay on A549 (human lung carcinoma epithelial like) cells. All of the tested compounds induced time‐ and concentration‐dependent cytotoxic effect.     

Isolation,Structure, and Biological Activities of Long-Chain Catechols of Plectranthus sylvestris (Labiatae)

Antioxidant activity guided fractionation of extracts of the aerial parts of the title plant and HPLC separation yielded a series of oxygenated long-chain alkylcatechols. Their structures were inferred by spectroscopic methods and chemical transformations to be the novel 4-[(2S,4R,6S)-4-(acetyloxy)tetrahydro-6-pentyl-2H-pyran-2-yl]benzene-1,2diol ( 1a ), 4-[(2S,4R6S)-tetrahydro-4-hydroxy-6-pentyl-2H-pyran-2-yl]benzene-1,2-diol ( 1b ), 4-[(3S,5S)-5-(acetyloxy)-3-hydroxydecyl]benzene-1,2-diol (2a), 4-[(3S,5S)3-(acetyloxy)-5-hydroxydecyl]benzene-1,2-diol ( 2b ), (3S,13Z)-1-(3,4-dihydroxyphenyl)-3-hydroxydocos-13-en-5-one ( 3a ), (Z)-1-(3,4-dihydroxyphenyl)docos-13-en-5-one ( 4 ), besides the known l-(3,4-dihydroxyphenyl)icosan-5-one ( 5 ). The absolute configurations of the optically active compounds which are structurally related to the [n]-gingerols ( 6 ) and -diols ( 7 ) were established by the high-field ¹H-NMR application of Mosher's method. All compounds are in vitro potent antioxidants, inhibiting the Fe²⁺-catalysed autoxidation of linoleic acid in the same order of magnitude as the commercial antioxidant 2,6-di(tert-butyl)-4-methylphenol (BHT). The dose-dependent inhibitory effects on soybean-lipoxygenase are in the μmol range, that of the most effective compound ( 3a ) in the nmol range, hence being significantly more potent than the Known anti-inflammatory and analgesic drugs indomethacin and nordihydroguaiaretic acid.     

Tolerance,bioaccumulation and biotransformation of arsenic in freshwater prawn (Macrobrachium rosenbergii)

Tolerance bioaccumulation and biotransformation of arsenic compounds by a freshwater prawn (Macrobrachium rosenbergii) were investigated. M. rosenbergii was exposed to 10, 20, 30 and 35 μg As cm⁻³ of disodium arsenate [abbreviated as As(V)], 25, 50, 100 and 120 μg As cm⁻³ of methylarsonic acid (MMAA), or 100,200, 300 and 350 μg As cm⁻³ of dimethylarsinic acid (DMAA). Tolerances (50% lethal concentration: LC₅₀) of the prawn against As(V), MMAA, and DMAA were 30, 100, and 300 μg As cm⁻³, respectively. The prawn accumulated arsenic compounds directly from aqueous phase and biotransformed them in part. Both methylation and demethylation of the arsenicals were observed in vivo. Highly methylated and less toxic arsenicals were less accumulated in M. rosenbergii.     

Tautomeric behavior of 3-(arylhydrazono)methyl-2-oxo-1,2-dihydroquinoxalines between the hydrazone imine and diazenyl enamine forms in acidic media. Solvent and substituent effects

The 3-(arylhydrazono)methyl-2-oxo-1,2-dihydroquinoxalines 1a-h and 2a-e showed tautomeric equilibria between the hydrazone imine A and diazenyl enamine B forms in a series of mixed trifluoroacetic acid/dimethyl sulfoxide media. The substituent and solvent effects on the tautomer ratios of A to B in a series of mixed media were studied for compounds 1a-h and 2a-e by the nmr spectroscopy. In compounds 1a-h and 2a-e , the ratios of the tautomer B gradually increased with elevation of acid concentration, and the tautomer B exclusively existed in trifluoroacetic acid media. The various acid concentrations (C v/v%, C' mol/1) giving the 1:1 tautomer ratios [C(A:B = 1:1), C'(A:B = 1:1)] were obtained from all compounds (Figures 1–13), and the linear correlation of the Hammett σ_p values with the log C'(A:B = 1:1) values were observed for compounds 1a-h. The larger Hammett σ_p values brought about the larger acid concentrations C(A:B = 1:1) in compounds 1a-h and 2a-e , indicating that the higher acid concentration was required for the stabilization of tautomer B possessing the electron-withdrawing p-substituents R¹, which weakened the basicity of the azo nitrogen atom. Moreover, the ester group R² of compounds 2a-e was found to decrease the electron density of the azo nitrogen atom, since the acid concentration C(A:B = 1:1) of compound 2c (R¹ = H, R² = COOMe, σ_p = O) was 52%, whose value was larger than that of compound 1b (R¹ = CN, R² = H, σ_p = 0.66) [C(A:B = 1:1) = 42%].     

Separation of six compounds from pigeon pea leaves by elution–extrusion counter‐current chromatography

A valid and reliable method was established to separate six compounds from pigeon pea leaves via elution‐extrusion counter‐current chromatography. A solvent system composed of n‐hexane/methanol/formic acid aqueous solution with pH = 3 (10:6:4, v/v) was screened to achieve satisfactory isolation from the ethanol extract of pigeon pea leaves. Four compounds, 9.2 mg of compound 1 (96.8%), 3.2 mg of 2 (88.0%), 6.2 mg of 4 (94.2%) and 25.2 mg of 5 (94.2%), were obtained by conventional elution from 100 mg of the precipitation fraction, respectively. Two compounds, 14.4 mg of 3 (96.3%) and 28.1 mg of 6 (96.6%), with high K values were obtained by the subsequent extrusion procedure. The compounds 1 – 6 were identified as 3‐methoxy‐5‐(2‐phenylethenyl)‐phenol, pinostrobin chalcone, pinostrobin, 2‐hydroxy‐4‐methoxy‐6‐(2‐phenylvinyl)‐benzoic acid, longistylin C and cajaninstilbene acid by quadrupole time‐of‐flight mass spectrometry, and ¹H and ¹³C NMR spectroscopy. The in vitro antiproliferation activities of compounds 1 , 5 and 6 against human hepatoma cell were evaluated and the half‐maximum inhibitory concentrations were acquired.     

Tupisteroide A–C,three new polyhydroxylated steroidal constituents from the roots of Tupistra chinensis

Three new steroidal compounds with polyhydroxy groups, tupisteroide A–C (1–3), were obtained from the roots of Tupistra chinensis, together with one known compound (4) that was isolated from this plant for the first time. The structures of tupisteroide A–C were determined on the basis of one‐ and two‐dimensional NMR spectroscopy, including ¹H–¹H Correlation Spectroscopy, Heteronuclear Multiple Bond Correlation, and Heteronuclear Single Quantum Coherence experiments. The isolated compounds were evaluated for their cytotoxic activities against A549, HepG2, and CaSki cancer cell lines in vitro. Among them, compounds 1, 2, and 4 did not show significant inhibitory activity, but compound 3 showed cytotoxicity against A549 cancer cell lines with IC₅₀ values of 25.0 μM. Copyright © 2012 John Wiley & Sons, Ltd.     

Iron(III) bis-complexes of Schiff bases of S-methyldithiocarbazates: Synthesis,structure, spectral and redox properties and cytotoxicity

A series of iron(III) bis-complexes of the type [FeL₂]X 1-4 , X = OH⁻ ( 1 ), Cl^¯ ( 3 ), and FeCl₄^¯ ( 2 , 4 ), where LH is a tridentate (N,N,S) ligands such as N′-(1-pyridin-2-ylethylidene)-hydrazinecarbodithioic acid methyl ester ( HL1 ), N′-(phenylpyridin-2-ylmethylene)-hydrazinecarbodithioic acid methyl ester ( HL2 ), N′-quinolin-2-ylmethylene-hydrazinecarbodithioic acid methyl ester ( HL3 ), or N′-(1-methyl-1H-imidazol-2-yl-methylene)hydrazinecarbodithioic acid methyl ester ( HL4 ) has been isolated in moderate to good yields and completely characterized by elemental analyses, conductivity studies, and infrared and UV-visible spectral measurements. The single crystal X-ray structures of 1 , 2 and 4 revealed that two deprotonated tridentate (NNS) ligands are meridionally coordinated to constitute a distorted octahedral coordination geometry around iron(III). In acetonitrile solution, all the complexes show quasi-reversible Fe(III)/Fe(II) redox behavior. The in vitro cytotoxicity of the ligands HL1–HL4 (IC₅₀: HL1 , 64.5; HL2 , 51.0; HL3 , 124.0; HL4 , 45.0 μM at 24 h) and complexes 1–4 (IC₅₀: 1 , 84.5; 2 , 40.0; 3 , 168.5; 4 , 50.5 μM at 24 h) towards A549 lung cancer cell lines are similar to cisplatin (69.0 μM), revealing that free ligands cause cancer cell death with potency higher than the corresponding iron(III) complexes. Also, both the ligands and the complexes cause cell death mainly through apoptotic mode, as revealed by the observation of a higher percentage of apoptotic cells in acridine orange (AO)/ ethidium bromide (EB), and Annexin V-Cy3 stained cancer cells.     

Triterpene Acids from the Leaves of Planchonella Duclitan (Blanco) Bakhuizan

From the methanolic extract of the leaves of Planchonella duclitan, 2α,3α,19α,23‐tetrahydroxy‐13,27‐cyclours‐11‐en‐28‐oic acid (1), myrianthic acid (2), 2‐hydroxyursolic acid (3), ursolic acid (4), pomolic acid (5), rotundic acid (6), and jacoumaric acid (7) were isolated, and their structures were elucidated on the basis of their spectroscopic analysis. Among them, compound 1 was a new cyclopropyl ursane‐type triterpene acid. Additionally, compounds 4 and 7 showed significant cytotoxicity toward human colorectal carcinoma cell line HT29 and human breast carcinoma cell line MCF‐7 with IC₅₀ values ranging from 5.8 ± 1.4 to 6.5 ± 1.9 μM.     

Synthesis and Antifungal Activity Evaluation of Novel Substituted Pyrimidine‐5‐Carboxamides Bearing the Pyridine Moiety

A series of novel N‐(substituted phenyl/benzyl)‐2‐methylthio‐4‐((pyridin‐3‐ylmethyl)amino)pyrimidine‐5‐carboxamides were synthesized by multistep reactions. The structures of the target compounds were characterized by IR, ¹H NMR, ¹³C NMR, and elemental analysis. Their in vitro antifungal activities against two kinds of plant pathogenic fungi were evaluated by the mycelial growth rate method. The result showed that at the dosage of 100 μg/mL, several of these compounds exhibited moderate activity against Botrytis cinerea with inhibition rates of ~70%, and most compounds (e.g., 5a , 5c , 5e , 5f, and 5h ) possessed excellent activity against Sclerotinia Sclerotiorum with more than 90% inhibition rate.