Antiinflammatory and antiproteolytic properties of substituted-4-thiazolidones

Eleven 3-(3,4-diamethoxy phenyl ethyl)-4-oxothiazolin-2-yl-substituted hydrozones were evaluated for antiinflammatory and antiproteolytic properties. The toxicity of the compounds was reflected by their approximate LD50 values.     

Photochemistry and photophysical properties of novel, unsymmetrically substituted metallophthalocyanines

In order to gain insight into the relation between health and people's environment, literature published between 1985 and 1994 was gathered from several international databases. An introduction into existing theory regarding geographic disparities is presented: geographical drift and breeder hypotheses are discussed. This is followed by a critical review focusing on interaction effects of urbanicity and individual characteristics on health. This leads to two major conclusions. First, emphasis in past research has been primarily on urban constraints rather than opportunities. Positive aspects of urban living are often insufficiently appreciated. Second, positive and negative environmental aspects have an effect on health that is often dependent on individual characteristics. The extent to which the environment exerts influence on a person's health is dependent on that person's individual characteristics. These conclusions are relevant only for further developing the breeder hypothesis, however. Large scale individual based longitudinal data should be studied in order to gain more insight into the relative importance of the geographical drift hypothesis.     

Spirobutenolides substituted by arylpiperazinyl-carbonyl moieties. Synthesis and antinociceptive properties

The synthesis and spectral data of some new cyclohexane-2-spiro-[2,5-dihydro-3-(N-arylpiperazin-1-yl-carbonyl) -4-methyl- 5-oxo]furanes are reported. These compounds were subjected to pharmacological tests for evaluation of antinociceptive effects and interactions with opioidergic and monoaminergic systems. With respective ED50 values of 116.4 and 87.0 mg/kg i.p., derivatives 2b and 2e were the most active spirobutenolides in the phenylbenzoquinone-induced writhing test (PBQ-test) without neurotoxic effects. They potentiated morphine analgesia and were also active at the dose of 150 mg/kg i.p. in the hot plate test while they exhibited sedative effects from the dose of 100 mg/kg i.p. In addition, 2b and 2e analgesia was antagonized by naloxone, then again potentiated by 5-hydroxytryptophan associated to carbidopa in the PBQ-test, demonstrating involvement of opioidergic and serotonergic pathways in the analgesic properties of both compounds. Furthermore, antinociceptive effects of 2e were attenuated by oral administration of yohimbine suggesting that its analgesic activity was also partly related to a noradrenergic mechanism.     

Novel ligand binding properties of the myoglobin substituted with monoazahemin

The iron complex of alpha-azamesoporphyrin XIII was combined with apomyoglobin to investigate influence of the meso nitrogen on ligand binding properties in the reconstituted protein. Stoichiometric complex formation between the two components was confirmed, and conservation of the native coordination structures in the resultant myoglobin was established with spectroscopic criteria and apparently normal ligand binding. The visible absorption spectra of various ferric and ferrous derivatives are characteristic with less intense Soret peaks and enhanced visible bands. The electron paramagnetic resonance spectrum with g = 5.2 suggests an anomalous intermediate spin (S = 3/2) character for the aquomet protein. The oxygen affinity of reduced azaheme myoglobin, 0.010 mm Hg, is 50 times larger than that of the native myoglobin. In addition, azaheme myoglobin forms stable complexes with imidazole, pyridine, or cyanide in ferrous state. All of these new properties were consistently explained in terms of stronger equatorial ligand field of the heme iron in a narrower coordination cavity. Similarities of azaheme to verdoheme were also pointed out.     

Magnetic properties of La-Zn substituted Sr-hexaferrites by self-propagation high-temperature synthesis

The La-Zn substituted SrM-type ferrites with the composition of Sr1-xLaxFe12-xZnxO19 （x=0-0.4） were prepared by self-propagating high-temperature synthesis （SHS）. The single SrM phase was detected by XRD in the as-received samples by controlling the Fe contents in the reagents. The substitution of La^3＋and Zn^2＋ obviously increased the magnetic properties of the as-prepared samples. The maximum improvements of Br, Hcb and （BH）m were 14.4%, 15.3% and 30.7%, respectively compared with that of the samples without La-Zn substitution. Microstructure observation by SEM showed that the SHS method benefited forming the better particle features and achieving the higher Hcj in comparison with the traditional firing method.     

Investigation of structural, magnetic and optical properties of rare earth substituted bismuth ferrite

Polycrystalline BiFeO3 and rare earth substituted Bi0.9R0.1FeO3(BRFO,R=Y,Ho and Er) compounds were prepared by rapid solid state sintering technique.Structural phase analysis indicated that all the compounds stabilized in rhombohedral structure(R3c space group) and a small orthorhombic phase fraction was observed in BRFO compounds.From the Raman spectra results,the changes in the phonon frequencies(A 1) and line widths suggested lattice distortion in the BRFO compounds as was evidenced in the XRD analysis.Compared to the linear variation of magnetization with magnetic field(M-H) shown by BFO,an obvious M-H loop was observed in BRFO compounds which could be due to the suppression of space modulated spin structure and was explained on the basis of weak ferromagnetism and field induced spin reorientation.UV-Vis spectroscopy evidenced a change in local FeO6 environment due to shift in the 6A1g → 4T2g energy transition band.BRFO compounds with improved remnant magnetization and coercive field are applicable for magnetoelectric devices.     

Synthesis and properties of covalently-closed DNA duplexes containing pyrophosphate and and substituted pyrophosphate internucleotide groups

A new method for the efficient synthesis of covalently closed DNA duplexes (DNA dumbbells) and the introduction of pyrophosphate and substituted pyrophosphate internucleotide groups into their structure is proposed. The method is based on chemical ligation in DNA duplexes that are formed by a polynucleotide the ends of which are brought together due to the introduction of the minihairpin structure [sequence: see text]. DNA dumbbells containing a pyrophosphate (substituted pyrophosphate) group result from the interaction as being between the 3'-terminal phosphate (methylphosphate) group of the polynucleotide and the 5'-terminal phosphate group of deoxyguanosine of the minihairpin sequence, which flanks the polynucleotide from the 5' end. 1-Ethyl-3-(3'-dimethylaminopropyl) carbodiimide was used as a condensing agent. The yield of covalently closed 42-mer DNA duplexes containing a pyrophosphate group was 98%, that of duplexes with a substituted pyrophosphate group was 25%. The reactivity of the substituted pyrophosphate group incorporated into DNA dumbbells was studied. It is shown that the group efficiently interacts with nucleophiles in an aqueous medium at pH 8.0.     

Synthesis and pharmacological properties of some new diphenylacetic acid amides substituted at the nitrogen atom

A 67-yr-old woman who ingested approximately 7 gm procainamide developed severe hypotension, renal insufficiency, and life-threatening cardiac toxicity. Hemodialysis doubled the rate of procainamide elimination and increased fourfold the clearance of NAPA, the N-acetylated metabolite of procainamide. Observations of procainamide and N-acetylprocainamide (NAPA) plasma levels during the patient's recovery suggest that lethargy and profound hypotension can be expected when these levels total 60 mug/ml and that severe cardiac toxicity should be anticipated with levels totaling 42 mug/ml or more. Hemodialysis also permitted investigation of the effects of hypotension on the pharmacokinetics of these compounds. The apparent volume of procainamide distribution was reduced from a normal value of 2 L/kg to 0.76 L/kg, and that of NAPA from 1.4 L/kg to 0.63 L/kg. The elimination + 1/2 of procainamide was prolonged from the normal of 3 hr to 10.5 hr, and that of NAPA from 6 to 35.9 hr. Procainamide absorption was also slowed in this clinical setting, causing procainamide plasma levels to continue rising for some time after toxicity was first recognized.     

fMLP-OMe analogs substituted at the methionine residue: an insight into the receptor properties

In order to obtain an insight into the mode of binding at the for-Met-Leu-Phe-OH (fMLP) receptor, three fMLP-OMe analogs (1-3) were synthesized in which the Met residue was substituted by Gln 1, Asn 2, and Ser 3. We evaluated the influence of the charge variation and/or the shift of its position on neutrophil biological responses.     

Synthesis of substituted anilino-3-methoxy-4-substituted acetoxy) benzylidenes and their monoamine oxidase inhibitory and anticonvulsant properties

Several substituted anilino-(3-methoxy-4-substituted acetoxy) benzylidenes were synthesized and characterized by their sharp melting points and elemental analyses. All substituted benzylidenes competitively inhibited the in vitro monoamine oxidase activity of rat brain homogenates and possessed anticonvulsant activity against pentylenetetrazol-induced convulsions in mice.     

Nanocrystals of magnesium and fluoride substituted hydroxyapatite

A series of novel platinum(IV) cisplatin analogues of the type [Pt(cis-1,4-DACH)trans-(L)2Cl2] (where cis-1,4-DACH = cis-1,4-diaminocyclohexane and L = acetate, propionate, butyrate, valerate, hexanoate, heptanoate, octanoate, nonanoate, or decanoate) was synthesized and characterized by elemental analysis, IR, 13C-NMR, and 195Pt-NMR spectroscopy. The structure of [Pt(cis-1,4-DACH)trans-(acetate)2Cl2] (1) was determined by X-ray crystallography. The crystals were monoclinic, space group P2(1)/n (no. 14) with a = 10.193(2), b = 10.687(2), c = 14.265(3) A, beta = 99.67(3) degrees, Z = 4. The total reflections collected were 2556. The structure refinement converged to R1 = 0.0539 and wR2 = 0.1531. In this complex, platinum has distorted octahedral geometry, and cis-1,4-DACH is in a unique twist-boat configuration. cis-1,4-DACH forms a seven-member chelating ring with platinum, leading to considerable strain in bidentate DACH binding. The strain is evidenced by a large 126.5(9) degrees C-N-Pt angle. The N-Pt-N angle is expanded to 97.4(5) degrees owing to geometric constraints of the cis-1,4-DACH geometry. Three lower homologs of the cis-1,4-DACH-Pt(IV) series were tested in the murine L1210/0 leukemia model for antitumor activity. The results indicate that activity decreases in ascending the homologous series, and that the activity of two of the complexes is substantially better than that of cisplatin with respect to increase in life span and cures.     

New esters of substituted anilinonicotinic and phenylanthranilic acids

In the search for new non-steroidal antiinflammatory drugs with low ulcerogenic activity, phthalidyl and pivaloyloxymethyl esters of anilinonicotinic and N-phenylanthranilic acids were synthesized. One of them, the 3-phthalidyl ester of 2-([3-(trifluoromethyl)phenyl]amino)-3-pyridinecarboxylic acid, also named talniflumate, showed lower ulcerogenic activity and toxicity and greater antiinflammatory activity than the niflumic acid.     

Role of composition and grain size in controlling the structure sensitive magnetic properties of Sm~(3+) substituted nanocrystalline Co-Zn ferrites

The nanocrystalline samarium substituted Co-Zn ferrites with chemical formula Co_(0.7)Zn_(0.3)SmyFe_(2-y)O_4(where y=0,0.01,0.02,0.03,0.04) were synthesized by sol-gel autocombustion route.The analysis of Xray diffractograms(XRD) reveals the formation of cubic spinel structure.The planes indexed from XRD analyses were confirmed in the selected area electron diffraction(SAED) image of the sample.Nanocrystalline nature of the particles in the ferrite samples was confirmed by TEM.The morphology was analyzed by scanning electron microscopy(SEM).Magnetic measurements show an increase in the magnetization for x ≤0.03.The decrease in magnetization due to spin canting is observed for x=0.04.The coercivity depends on Sm~(3+)doping concentration,grain size and saturation magnetization.The complex permeability of the ferrites was analyzed as the function of frequency and Sm~(3+)composition(y).The real part of complex permeability varies linearly with the grain size.     

Effects and risks of substituted amphetamines (Ecstasy)]

In a consecutive series of 174 children with low-level spina bifida, there was hindfoot deformity in 263 of the 348 feet; 86 were in equinus, 108 were in calcaneus, 41 were in valgus, 20 were in varus, and eight had convex pes valgus. Surgery was performed on 222 (64%) feet. The deformities were symmetric in 114 children. Spasticity causing deformity necessitated surgery in only 44 feet. Calcaneus deformity in the foot is considerably more common in patients with L4 lesions, and in these circumstances, muscle imbalance is clearly a major factor. However, many patients with calcaneus deformity had L5 or sacral lesions. This suggests that muscle imbalance is not so important a factor as has been thought in the causation of deformity in the lower limb in myelomeningocele.     

Platinum complexes of substituted ethylenediamines and their anti-tumour activity

A large number of substituted ethylenediamine complexes of platinum (II) and platinum(IV) have been prepared and characterised, and their anti-tumour activity tested against sarcoma 180, leukemia L1210, and ADJ/PC6A plasma cell tumours. In general these complexes are less active than simpler amine analogues, though several complexes show activity against all of the screens. Difference in activity of platinum(II) and platinum(IV) analogues leads us to cast doubt on the "in vivo reduction" theory hitherto used to describe the action of platinum(IV) complexes.     

Antimycobacterial activity of substituted isosteres of pyridine- and pyrazinecarboxylic acids

Pyrazines and pyridines substituted with alkylated tetrazoles, esterified vinylogous carboxylic acids, and ketosulfides were synthesized as precursors of antimycobacterial agents which, after penetration of the mycobacterial cell wall, could be biotransformed by esterases or peroxidase-catalases. The expected products are tetrazoles, a vinylogous carboxylic acid, and CH-acidic ketosulfoxides, isosteres of pyrazinoic and nicotinic acids, which should inhibit mycobacterial growth when released inside the bacterial cell. The growth inhibitory activity of the synthesized compounds against the H37Rv strain of Mycobacterium tuberculosis was determined to assess the viability of this concept. It was shown that all of the compounds designed as lipophilic precursors were more active than the unmodified polar isosteres of pyrazinoic and nicotinic acids.     

Synthesis, properties and biological evaluation of substituted furo[3,2-e] and pyrano[3,2-e]pyrido[4,3-b]indoles

Furo[3,2-e]- and pyrano[3,2-e]pyrido[4,3-b] indoles were synthesized from 1,4,5-trisubstituted 8-hydroxy-5H-pyrido[4,3-b]indoles. The intermediates, 10-chloro-6H-furo[3,2-e]pyrido[4,3-b]indole (11), 10-chloro-2,6-dihydro-1H-furo[3,2-e]pyrido-[4,3-b]indole (10) and 11-chloro-2,3-dihydro-3H,7H-pyrano[3,2-e]pyrido[4,3-b]indole (15), were substituted by diamines under thermal conditions (180 degrees C). In contrast, 11-chloro-3H,7H-pyrano[3,2-e]pyrido[4,3-b]indole (14), 9-allyl-1-chloro-4,5-dimethyl-5H-pyrido[4,3-b]indole (9a) and 8-propargyloxy-4,5-dimethyl-5H-pyrido[4,3-b]indole (8) led mainly to 1-aminosubstituted 8-hydroxy-5H-pyrido[4,3-b]indole derivatives resulting from an unexpected C3 unit elimination. When examined in three tumour cell lines (L1210 leukaemia, the B16 melanoma and the MCF7 breast adenocarcinoma) the new amino substituted furo[3,2-e]-, dihydrofuro[3,2-e]- and dihydropyrano[3,2-e]-pyrido[4,3-b]indole derivatives revealed cytotoxic properties, especially important for the 2,6-dihydro-1H-furo[3,2-e]pyrido[4,3-b]indole series. The most active compound (12b) significantly inhibits both DNA topoisomerases I and II, and is as potent as Adriamycin at inhibiting cell proliferation and inducing a massive accumulation of L1210 cells in the G2 + M phase of the cell cycle. However, 12b was less active than Adriamycin when tested in vivo against P388 leukaemia or the B16 melanoma tumour models.