Inhibition of radish germination and root growth by coumarin and phenylpropanoids

Thirteen natural and synthetic phenylpropanoids as well as coumarin (2×10⁴M) were tested for their biological activity on radish germination and subsequent root growth in light and darkness. Coumarin was the most potent inhibitor. With some exceptions, phenylpropanoids with a carboxylic group in the side chain inhibited root growth. Coumarin was formed spontaneously by photooxidation of 2-hydroxycinnamic acid. Microscopic observations of root treated with coumarin suggest that this substance inhibits the elongation of cells of the differentiating zone of the root.     

Absence of farnesol in strawberry and hop foliage

The farnesol content of foliage has been proposed as an indicator of susceptibility to the two-spotted spider mite in various crops. The use of this chemical marker was investigated for strawberry and hop varieties. No farnesol was detectable in any of the varieties tested. The techniques necessary for analysis and identification of farnesol from foliage are discussed.     

Inhibition of growth of the green algaChlorella pyrenoidosa by unsaturated fatty acids

The activity of a number of unsaturated fatty acids in inhibiting the growth of the green algaChlorella pyrenoidosa has been studied using the paper disk-agar plate method. Acrylic and undecylenic acids were highly active, but other θ-unsaturated fatty acids tested were only weakly active. Oleic and elaidic acids were inactive at 0.2 M, but other C₁₈-C₂₂ acids with 2 to 6 double bonds were generally active down to a concentration of 0.01–0.005 M. Activity with chaulmoogric acid was noted down at 0.002–0.001 M. Diffusion rates of the acids through the agar seem to affect the size of the inhibition zones. The implications that polyunsaturated fatty acids may play a role in algal ecology are discussed.     

Inhibition of phenytoin bioactivation and teratogenicity by dietary n−3 fatty acids in mice

Evidence suggests that the teratogenicity of the anticonvulsant drug phenytoin (DPH) can result from its bioactivationvia embryonic prostaglandin synthase and/or maternal cytochromes P450. This study examined whether DPH bioactivation and teratogenicity could be reduced by dietary n−3 fatty acids. Female CD-1 mice were fed diets containing 2 wt% safflower oil and 10 wt% of either hydrogenated coconut oil, safflower oil, or a cod liver oil/linseed oil mixture (CLO/LO) for three weeks prior to impregnation and throughout gestation. DPH (55 or 65 mg/kg) was administeredvia intraperitoneal injections to pregnant mice at 0900 on gestational days 12 and 13, and on day 19 fetuses were given teratologic assessments. A similar dietary study evaluatedin vivo covalent binding of radiolabeled DPH administered on day 12, and dams were killed 24 h later. A reduction in DPH-induced cleft palates and a decrease in DPH covalent binding to embryonic protein was observed in the CLO/LO group. Feeding CLO/LO enhanced incorporation of n−3 fatty acids into embryos and inhibited embryonic prostaglandin synthase activity. No differences in maternal hepatic cytochromes P450 activities were observed among dietary treatments. These data indicate that dietary n−3 fatty acids could reduce DPH teratogenicityvia inhibition of embryonic prostaglandin synthase bioactivation of DPH. Presented in part at the annual meeting of the Federation of the American Societies for Experimental Biology, New Orleans, LA, May 1989 [Kubow, S. (1989)FASEB J. 3, A726] and at the annual meeting of the Canadian Federation of Biological Societies, Kingston, Ontario, Canada, June 1991 [Kubow, S. (1991)Proc. Can. Biol. Soc. 34, 117].     

Dietary fat and the development of pancreatic cancer

Pancreatic cancer is the fifth most common cause of death due to cancer. Except for an association with cigarette smoking, its etiology is poorly understood. Because of the dearth of epidemiological clues as to causation, studies with experiemntal animal models assume greater importance. Rodent models of pancreatic cancer indicate that while dietary fatper se does not cause pancreatic cancer, it does enhance or promote tumor development. Subsequent to treatment with a pancreatic carcinogen, high intakes of dietary unsaturated fats of the n−6 series, but not saturated fats, enhance or promote tumor development. A requisite level of linoleic acid is needed for this promotion. Fats of the n−3 series (e.g., certain fish oils) are inhibitory to tumor growth. Promotion by dietary fats appears only partly related to the high caloric content of fat. Mechanistically, certain dietary unsaturated fats appear to selectively enhance the growth rate of carcinogeninduced, pre-cancerous lesions. Irrespective of precise understanding of mechanisms of promotion, it, appears possible to intervene in the process of cancer development and reduce the burden of cancer. Experimentally, this may be accomplished by decreasing total fat intake, decreasing caloric intake, increasing exercise or increasing the intake of n−3 fatty acids. Based on a paper presented at the Symposium on Lipids in Cancer held at the AOCS Annual Meeting, Baltimore, MD, April 1990.     

Functional copolymer of geraniol and acrylonitrile: Synthesis and characterization

The radical copolymerization of acyclic terpene namely geraniol [GER] with acrylonitrile [AN] in DMF at (70 ± 0.1)°C for 1 h, using benzoylperoxide (BPO) as an initiator has been carried out under inert atmosphere of nitrogen. The kinetic expression for reaction is R_p ∝ [BPO]^0.5 [AN]^1.0 [GER]^1.0. The IR spectrum of the copolymer shows bands at 3432 and at 2244 cm^?1 due to ? OH group of GER and ? CN group of AN, respectively. The ¹³C‐NMR spectrum shows peaks at 73–75 δ ppm and 116–120 δ ppm due to ? OH group of GER and ? CN group of AN, respectively. The thermogravimetric analysis and differential scanning calorimetry study shows that copolymer is thermally stable up to 407°C and has glass transition temperatures (T_g) 56°C. The reactivity ratios r₁ (AN) and r₂ (GER) have been calculated as 0.05 and 0.005, respectively. The Alfrey‐Price Q‐e parameter for GER has been calculated as 0.094 and ?2.0, respectively. The molecular weights of the copolymers have been evaluated by gel‐permeation chromatography. © 2008 Wiley Periodicals, Inc. J Appl Polym Sci, 2008     

Inhibition of cell growth by a fused protein of human ribonuclease 1 and human basic fibroblast growth factor

Pancreatic-type RNases are considered to have cytotoxic potentialdue to their ability to degrade RNA molecules when they enterthe cytosol. However, most of these RNases show little cytotoxicitybecause cells have no active uptake mechanism for these RNasesand because the ubiquitous cytoplasmic RNase inhibitor is consideredto play a protective role against the endocytotic leak of RNasesfrom the outside of cells. To study the cytotoxic potentialof RNase toward malignant cells targeting growth factor receptors,the C-terminus of human RNase 1 was fused to the N-terminusof human basic fibroblast growth factor (bFGF). This RNase–FGFfused protein effectively inhibited the growth of mouse melanomacell line B16/BL6 with high levels of cell surface FGF receptor.This effect appeared to result from prolongation of the overallcell cycle rather than the killing of cells or specific arrestin a particular phase of the cell cycle. Thus, human RNase 1fused to a ligand of cell surface molecules, such as the FGFreceptor, is shown to be an effective candidate for a selectivecell targeting agent with low toxic effects on normal cell types.     

Inhibition of the growth of the red microalga porphyridium sp. by limitation of nutrient transfer

The unicellular red alga Porphyridium sp. was cultured in a medium to which increasing concentrations of its cell wall polysaccharide were added. As the polysaccharide concentration in the culture medium increased, algal growth rate and maximum cell number progressively decreased. In a different series of experiments it was shown that the polysaccharide also inhibited the rate of carbon uptake by the cells and as a result photosynthesis was also inhibited. In-vitro experiments showed that the mass transfer coefficient for nitrate, bicarbonate, phosphate and potassium decreased as the polysaccharide concentration increased. The data indicate that the polysaccharide inhibits nutrient transfer from the medium to the cells, resulting in a reduction of the growth rate.     

Influence of dietary fats on pancreatic phospholipids of chronically ethanol-treated rats

Male rats were given liquid diets by pair-feeding for 24–30 days, and phosphatidylinositols in pancreas were analyzed as derivatives of diacylglycerols and fatty acids. Addition of arachidonic acid or changing the fat component (35 energy%) in the liquid diet from olive oil/corn oil to oil fromBorago officinalis, which contains 22% γ-linolenic acid, increased the fraction of arachidonoyl-containing species. This fraction was decreased by more than 50% by substituting ethanol for 36 of the 47 energy% provided by carbohydrate. A smaller difference between ethanol-fed and control rats was seen in the composition of phosphatidylcholines and phosphatidylethanolamines. There was no difference in the composition of phosphatidylinositols when fat, instead of ethanol, was used to substitute the 36 energy% in the diet containing olive oil/corn oil. Substituting ethanol for 28 of 35 energy% provided by fat as corn oil in a liquid diet had no effect on the fraction of arachidonoyl-containing species. The results indicate that the effect of ethanol on phosphatidylinositols in pancreas is not due to a deficiency of arachidonic acid, and that the effect of the ethanol-containing diet is not due to the lowered carbohydrate content. However, high contents of fat or of ethanol appear to be necessary for the effect.     

Interaction of dietary intake and diarrheal disease in child growth

There is evidence in the literature of the negative effects of diarrheal disease, and of the positive effects caused by food supplementation in postnatal growth. The present study analyzes the nature of the relationship between the effects of diarrheal disease and food supplementation on the growth of children of a rural area of Guatemala. The data analyzed were collected in a longitudinal study on food supplementation carried out by INCAP during the period comprised between 1969 and 1977. An important negative effect of diarrheal disease on growth was found on children three to 36 months of age with low dietary intake. Nevertheless, it was found that the negative effect of diarrheal disease on growth was lower in children whose dietary intake had important increments. In contrast, as compared with a study carried out in Colombia, where the supplementary feeding effect was restricted to groups with higher incidence of diarrhea, the supplementation effect on growth of Guatemalan children was found to be present at all levels of prevalence of diarrheal diseases. This article discusses the possible causes of the different results found in the Colombian study, as compared with those derived from the present study.     

Production of geranyl propionate by enzymatic esterification of geraniol and propionic acid in solvent‐free system

Background: This work reports the optimization of geranyl propionate production by esterification of geraniol and propionic acid in a solvent‐free system using a commercial lipase as catalyst. For this purpose, a sequential strategy was performed applying two experimental designs. Results: The operating conditions that optimized geranyl propionate production were determined to be 40 °C, geraniol to propionic acid molar ratio of 3:1, 150 rpm and 10 wt% of enzyme, with a resulting reaction conversion of about 93%. After determining the optimum reaction parameters, a kinetic study was carried out evaluating the influence of substrates molar ratio, enzyme concentration and temperature on reaction conversion. Results obtained in this step allow one to conclude that an excess of alcohol (acid to alcohol molar ratio of 1:6), relatively low enzyme concentration (5 wt%), temperature of 40 °C and substrates molar ratio of 1:1 afforded nearly complete reaction conversion after 30 min of reaction. Conclusion: New experimental data on enzymatic esterification of geraniol and propionic acid for geranyl propionate production are reported in this work, showing a promising perspective of the technique to overcome the well‐known drawbacks of the chemical‐catalyzed route. Copyright © 2010 Society of Chemical Industry     

Inhibition of grain growth in liquid-phase sintered SiC ceramics by AlN additive and spark plasma sintering

SiC ceramics were prepared from nanosized β-SiC powder with different compositions of AlN and Y₂O₃ sintering additives by spark plasma sintering (SPS) at 1900 °C for 600 s in N₂. The relative density of the sintered SiC specimens increased with increasing amount of AlN, reaching a relative density higher than 99%, while at the same time grain size decreased significantly. The smallest average grain size of 150 nm was observed for SiC sample sintered with 10 vol% of additives consisting of 90 mol% AlN and 10 mol% Y₂O₃. Fully dense nanostructured SiC ceramics with inhibited grain growth were obtained by the AlN additive and SPS technique. The flexural strength of the SiC body containing 70 mol% AlN and 30 mol% Y₂O₃ additives reached the maximum value of 1000 MPa. The SiC bodies prepared with AlN and Y₂O₃ additives had the fracture toughness of around 2.5 MPam^1/2.     

Chemistry, biology, and QSAR studies of substituted biaryl hydroxamates and mercaptoacetamides as HDAC inhibitors-nanomolar-potency inhibitors of pancreatic cancer cell growth

The histone deacetylases (HDACs) are able to regulate gene expression, and inhibitors of the HDACs (HDACIs) hold promise in the treatment of cancer as well as a variety of neurodegenerative diseases. To investigate the potential for isoform selectivity in the inhibition of HDACs, we prepared a small series of 2,4'-diaminobiphenyl ligands functionalized at the para-amino group with an appendage containing either a hydroxamate or a mercaptoacetamide group and coupled to an amino acid residue at the ortho-amino group. A smaller series of substituted phenylthiazoles was also explored. Some of these newly synthesized ligands show low-nanomolar potency in HDAC inhibition assays and display micromolar to low-nanomolar IC(50) values in tests against five pancreatic cancer cell lines. The isoform selectivity of these ligands for class I HDACs (HDAC1-3 and 8) and class IIb HDACs (HDAC6 and 10) together with QSAR studies of their correlation with lipophilicity are presented. Of particular interest is the selectivity of the mercaptoacetamides for HDAC6.     

Inhibition of seedling growth of crop species by recirculating root exudates ofBidens pilosa L.

The allelopathic effects of root exudates ofBidens pilosa L. on seedling growth ofLactuca sativa L.,Phaseolus vulgaris L.,Zea mays L., andSorghum bicolor (L.) Moench were studied using a root exudate recirculating system that allows continuous exposure of crop plants to allelopathic chemicals. This system maintains an undisturbed rhizosphere and eliminates competition and physical contact between the donor and acceptor plants. Comparison of responses to hydrophobic and hydrophilic root exudates is made possible by removal of hydrophobic compounds using XAD-4. Treatments consisted ofB. pilosa, B. pilosa with an Amberlite XAD-4 resin column attached to the donor pot to remove hydrophobic allelochemicals, and a donor pot without weeds.B. pilosa significantly inhibited seedling growth of all crop species tested. The crop species varied in response to the root exudates, withL. sativa being most sensitive. Larger and olderB. pilosa plants caused greater inhibition of seedling growth ofL. sativa andP. vulgaris than did smaller (younger)B. pilosa plants.B. pilosa with XAD-4 caused significantly less inhibition to all crop species, exceptZ. mays, thanB. pilosa without XAD-4, indicating that the hydrophobic exudates played an important role in the allelopathic growth inhibition. Variability in species response toB. pilosa with and without XAD-4 was probably due to differences in sensitivity to hydophobic and hydrophilic allelochemicals.Supported by a grant under USDA Agreement No. 83-CRSR-2-2293. Journal Series No. 2887 of the Hawaii Institute of Tropical Agriculture and Human Resources.     

Inhibition of abnormal grain growth in BaTiO3 by addition of Al2O3

The effect of additions of up to 1 mol% Al₂O₃ on abnormal grain growth in BaTiO₃ samples sintered at 1200 and 1250 °C has been studied. Samples with and without additions of 0.4 mol% TiO₂ were prepared. For the samples without added TiO₂, addition of 0.1 mol% Al₂O₃ increases the number density of abnormal grains, with further additions reducing the number density. The initial increase in number density is caused by Al₂O₃ forming a solid solution with BaTiO₃ and releasing TiO₂ to the grain boundaries. This excess TiO₂ then reacts with BaTiO₃ to form Ba₆Ti₁₇O₄₀, which promotes {1 1 1} twin formation and abnormal grain growth. Further additions of Al₂O₃ react with BaTiO₃, Ba₆Ti₁₇O₄₀ and excess TiO₂ to form Ba₄Al₂Ti₁₀O₂₇ and BaAl₂O₄ second phases, neither of which are growth sites for abnormal grains. For the samples with added TiO₂, addition of Al₂O₃ decreases the number of abnormal grains due to the Al₂O₃ reacting with the excess TiO₂ and BaTiO₃ to form Ba₄Al₂Ti₁₀O₂₇ and BaAl₂O₄ instead of Ba₆Ti₁₇O₄₀.     

Inhibition of growth ofPhytophthora parasitica var.nicotianae by aromatic acids and coumarins in a laboratory bioassay

Hydroxy-, dihydroxy-, trihydroxy-, methoxy-, dimethoxy-, hydroxy-+methoxy-, amino-, chloro-, and nitro-substituted benzoic, phenylacetic, phenylpropanoic, and phenylpropenoic (cinnamic) acids were evaluated for activity against the growth ofPhytophthora parasitica var.Nicotianae, Races 0 and 1, in a laboratory bioassay. Several substituted coumarins were also tested. In general, for Race 0, the phenylpropenoic acids were more active (on a millimolar basis), than the corresponding benzoic, phenylacetic, or phenylpropionic acids (9 of 14 series). Among the most active acids wereo-hydroxycinnamic and the chloro- and methoxycinnamic acids. The activities of unsubstituted benzoic and phenylpropionic acids were comparable to the most active compounds tested. Monohydroxyaromatic acids were more active than most dihydroxy acids of the same chain length. Dihydro-3,4-dihydroxycinnamic acid was slightly more active than the corresponding cinnamic acid, while the reverse was true for the mono-p-hydroxycinnamic acid versusp-hydroxyphenylpropionic acid. Coumarin was more active than its hydroxy, methyl, hydroxymethyl, or methoxy derivatives. In general, Race 1 was even more significantly affected by the aromatic acids. Glycosylated coumarins were inactive in the bioassay, compared to their aglycones.     

Tolerance and incorporation of a high-dose eicosapentaenoic acid diester emulsion by patients with pancreatic cancer cachexia

Chemotherapy and radiotherapy offer little benefit to patients with advanced pancreatic cancer. Eicosapentaenoic acid (EPA) has anticancer effects both in vitro and in animal models. The dose of EPA that can be administered to cancer patients has previously been limited by the low purity of available preparations and the tolerability of large capsules. A high-purity preparation of EPA as a 20% oil-in-water diester emulsion allowed a small study of the tolerance, incorporation, and effects of EPA in high doses in five patients with advanced pancreatic cancer. Patients underwent assessment at baseline and every 4 wk thereafter. All patients managed to tolerate a dose providing 18 g EPA per day, with doses between 9 and 27 g daily being taken for at least a month. Dosage was limited by a sensation of fullness, cramping abdominal pain, steatorrhea, and nausea. All such symptoms were controlled by dose reduction or pancreatic enzyme supplements. No other adverse effects attributable to the trial agent were observed. Plasma phospholipid EPA content increased from around 1% at baseline to 10% at 4 wk and 20% at 8 wk. Incorporation of EPA into red blood cell phospholipids reached levels of around 10%. The present study has shown that a novel, high-purity, EPA diester emulsion can be tolerated at a dose providing around 18 g EPA per day with side-effects being easily controlled. The acceptibility of large doses of oral EPA should allow larger controlled clinical studies into potential anticancer effects of EPA.