Isobutyl amides - potent compounds for controlling Diatraea saccharalis

BACKGROUND: A dichloromethane-methanol extract of the seeds of Piper tuberculatum Jacq. (Piperaceae) and two isobutyl amides, 4,5-dihydropiperlonguminine (1) and pellitorine (2), which were isolated by chromatographic methods, were assayed for their lethality against the sugarcane borer Diatraea saccharalis F. (Lepidoptera: Pyralidae). RESULTS: Bioassays were carried out with fourth-instar caterpillars through topical application of test solutions to the dorsal surface of the prothorax, and dose-response correlations were determined. Significant insect mortalities were observed 24, 48 and 72 h after treatment at concentrations of >= 100 mu g insect(-1). The LD(50) and LD(90) values for compound 1 were 92.83 and 176.50 mu g insect(-1), and for compound 2 they were 91.19 and 184.56 mu g insect(-1). CONCLUSION: According to the LD(50) and LD(90) for compounds 1 and 2, it can be inferred that the values reflect an acute lethal response to both compounds, based on interaction(s) of the toxicants with a primary target or series of targets. Thus, the amides were demonstrated to have potential value in the control of the sugarcane borer. (C) 2008 Society of Chemical Industry

In situ gelling hexagonal phases for sustained release of an anti-addiction drug

In this study, fluid precursor formulations for subcutaneous injection and in situ formation of hexagonal phase gels upon water absorption were developed as a strategy to sustain the release of naltrexone, a drug used for treatment of drug addiction. Precursor formulations were obtained by combining BRIJ 97 with propylene glycol (PG, 5-70%, w/w). To study the phase behavior of these formulations, water was added at 10-90% (w/w), and the resulting systems were characterized by polarized light microscopy. Two precursor formulations containing BRIJ:PG at 95:5 (w/w, referred to as BRIJ-95) and at 80:20 (w/w, referred to as BRIJ-80) were chosen. Naltrexone was dissolved at 1% or suspended at 5% (w/w). Precursor formulations were transformed into hexagonal phases when water content exceeded 20%. Water uptake followed second-order kinetics, and after 2-4 h all precursor formulations were transformed into hexagonal phases. Drug release was prolonged by the precursor formulations (compared to a drug solution in PBS), and followed pseudo-first order kinetics regardless of naltrexone concentration. The release from BRIJ-80 was significantly higher than that from BRIJ-95 after 48 h. The relative safety of the precursor formulations was assessed in cultured fibroblasts. Even though BRIJ-95 was more cytotoxic than BRIJ-80, both precursor formulations were significantly less cytotoxic than sodium lauryl sulfate (considered moderate-to-severe irritant) at the same concentration (up to 50 mu g/mL). These results suggest the potential of BRIJ-based precursor formulations for sustained naltrexone release. (C) 2011 Elsevier By. All rights reserved.

Production and characteristics comparison of crude beta-glucosidases produced by microorganisms Thermoascus aurantiacus e Aureobasidium pullulans in agricultural wastes

The purified beta-glucosidase of Aureobasidium pullulans ER-16 is one of more thermostable enzyme reported to date. Considering the unfeasibility of using purified enzyme for industrial application, it was interesting to analyze this property for the crude enzyme. Thermophilic fungus Thermoascus aurantiacus CBMAI-756 and mesophilic A. pullulans ER-16 were cultivated in different hemicellulosic materials on solid-state cultivation for beta-glucosidase production. Wheat bran was most appropriate for beta-glucosidase production by both microorganisms. T. aurantiacus exhibited maximum enzyme production (7.0 U/ml or 70 U/g) at 48-72 h and A. pullulans a maximum (1.3 U/ml or 13 U/g) at 120 h. Maximum activities were at 75 degrees C with optimum pH at 4.5 and 4.0, for T aurantiacus and A. pullulans, respectively. A. pullulans`s beta-glucosidase was more pH stable (4.5-10.0 against 4.5-8.0) and more thermostable (90% after 1 h at 75 degrees C against 85% after 1 h at 70 degrees C) than the enzyme from the thermophilic T. aurantiacus. The t((1/2)) at 80 degrees C were 50 and 12.5 min for A. pullulans and T. aurantiascus, respectively. These data confirm the high thermostability of crude beta-glucosidase from A. pullulans. Both beta-glucosidases were strongly inhibited by glucose, but ethanol significantly increased the activity of the enzyme from T. aurantiacus. (C) 2008 Elsevier Inc. All rights reserved.

In Vivo Antigenotoxicity of Baccharin, an Important Constituent of Baccharis dracunculifolia DC (Asteraceae)

Baccharin (3-prenyl-4-(dihydrocinnamoyloxy)cinnamic acid) is an important chemical compound isolated from the aerial parts of Baccharis dracunculifolia DC (Asteraceae), a native plant of South America, and the most important plant source of Brazilian green propolis. The present study was designed to investigate the ability of baccharin to modulate the genotoxic effects induced by doxorubicin and methyl methanesulphonate in male Swiss mice using the micronucleus and comet assays, respectively. The different doses of baccharin [0.12, 0.24 and 0.48 mg/kg body-weight (b.w.)] were administered simultaneously to doxorubicin (micronucleus test; 15 mg/kg b.w.) and to methyl methanesulphonate (comet assay; 40 mg/kg b.w.). The results showed a significant decrease in the frequency of micronucleated polychromatic erythrocytes in animals treated with baccharin and doxorubicin compared to animals that received only doxorubicin. This reduction ranged from 39.8% to 50.7% in the micronucleus test. The extent of DNA damage in liver cells was significantly lower in animals treated with different concentrations of baccharin combined with methyl methanesulphonate in comparison with the damage observed for animals treated only with methyl methanesulphonate. These differences resulted in a significant reduction in the extent of DNA damage, which ranged from 47.8% to 60.6%.

Antiviral and antiparasite properties of an L-amino acid oxidase from the Snake Bothrops jararaca: Cloning and identification of a complete cDNA sequence (Retracted article. See vol. 80, pg. 288, 2010)

L-Amino acid oxidases (LAAOs, EC 1.4.3.2) are flavoenzymes that catalyze the stereospecific oxidative deamination of an L-amino acid substrate to the corresponding a-ketoacid with hydrogen peroxide and ammonia production. The present work describes the first report on the antiviral (Dengue virus) and antiprotozoal (trypanocidal and leishmanicide) activities of a Bothrops jararaca L-amino acid oxidase (BjarLAAO-I) and identify its cDNA sequence. Antiparasite effects were inhibited by catalase, suggesting that they are mediated by H(2)O(2) production. Cells infected with DENV-3 virus previously treated with BjarLAAO-I, showed a decrease in viral titer (13-83-fold) when compared with cells infected with untreated viruses. Untreated and treated promastigotes (T. cruzi and L. amazonensis) were observed by transmission electron microscopy with different degrees of damage. Its complete cDNA sequence, with 1452 bp, encoded an open reading frame of 484 amino acid residues with a theoretical molecular weight and pl of 54,771.8 and 5.7, respectively. The cDNA-deduced amino acid sequence of BjarLAAO shows high identity to LAAOs from other snake venoms. Further investigations will be focused on the related molecular and functional correlation of these enzymes. Such a study should provide valuable information for the therapeutic development of new generations of microbicidal drugs. (C) 2008 Elsevier Inc. All rights reserved.

In vitro Antitumour Activity of Orsellinates

Lichen phenolic compounds exhibit antioxidant, antimicrobial, antiproliferative. and cytotoxic activities. The purpose of this study was to evaluate the anticancer activity of lecanoric acid, a secondary metabolite of the lichen Parmotrema tinctorum, and its derivatives, orsellinates, obtained by structural modification. A cytotoxicity assay was carried out hi vitro with sulforhodamine B (SRB) using HEp-2 larynx carcinoma, MCF7 breast carcinoma, 786-0 kidney carcinoma, and B16-F10 murine melanoma cell lines, in addition to a normal (Vero) cell line in order to calculate the selectivity index of the compounds. n-Butyl orsellinate was the most active compound, with IC(50) Values (the concentration that inhibits 50% of growth) ranging from 7.2 to 14.0 mu g/ml, against all the cell lines tested. The compound was more active (IC(50), = 11.4 mu g/mL) against B16-F10 cells than was cisplatin (12.5 mu g/mL). Conversely, lecanoric acid and methyl orsellinate were less active against all cell lines, having an IC(50) value higher than 50 mu g/mL. Ethyl orsellinate was more active against HEp-2 than against MCF7, 786-0, or B16-F10 cells. The same pattern was observed for n-propyl and n-butyl orsellinates. n-Pentyl orsellinate was less active than n-propyl or n-butyl orsellinates against HEp-2 cells. The orsellinate activity increased with chain elongation (from methyl to n-butyl), a likely consequence of an increase in lipophilicity. The results revealed that the structural modification of lecanoric acid increases the cytotoxic activity of the derivatives tested.

Demonstration of an ecdysis-triggering compound in the epitracheal gland of the cotton bollworm, Helicoverpa armigera (Hubner) (Lepidoptera : Noctuidae)

The recent report of an ecdysis-triggering hormone (ETH) in the tobacco hornworm Manduca sexta and several other Lepidoptera prompted the search for the homologous hormone in the pest noctuid, Helicoverpa armigera. In M. sexta, ETH is produced in a large cell that forms part of a three-cell epitracheal gland complex found near each of the the larval and pupal spiracles. The homologous glands were found in H. armigera and an ecdysis-triggering function of the gland contents was confirmed by the induction of premature ecdysis after injection of a crude gland extract into pupae.

The solution structure of a copper(II) compound of a new cyclic octapeptide by EPR spectroscopy and force field calculations

A new cyclic octapeptide, cyclo(Ile-Ser-(Gly)Thz-Ile-Thr-(Gly)Thz) (PatN), related to patellamide A, has been synthesized and reacted with copper(II) and base to form mono- and dinuclear complexes. The coordination environments around copper(TI) have been characterized by EPR spectroscopy. The solution structure of the thermodynamically most stable product, a purple dicopper(TI) compound, has been examined by simulating weakly dipole-dipole coupled EPR spectra based upon structural parameters obtained from force field (MM and MD) calculations. The MM-EPR method produces a saddle-shaped structure for [Cu-2(PatN)(OH2)(6)] that is similar to the known solution structure of patellamide A and the known solid-state structure of [Cu-2(AscidH(2))CO3(OH2)(2)]. Compared with the latter, [Cu-2(PatN)] has no carbonate bridge and a significantly flatter topology. The MM-EPR approach to solution-structure determination for paramagnetic metallopeptides may find wide applications to other metallopeptides and metalloproteins.

Development and characterization of novel potent and stable inhibitors of endopeptidase EC 3.4.24.15

Solid-phase synthesis was used to prepare a series of modifications to the selective and potent inhibitor of endopeptidase EC 3.4.24.15 (EP24.15), N-[1(R,S)-carboxy-3-phenylpropyl]-Ala-Ala-Tyr-p-aminobenzoate (cFP), which is degraded at the Ala-Tyr bond, thus severely limiting its utility in vivo. Reducing the amide bond between the Ala and Tyr decreased the potency of the inhibitor to 1/1000. However, the replacement of the second alanine residue immediately adjacent to the tyrosine with alpha-aminoisobutyric acid gave a compound (JA-2) that was equipotent with cFP, with a K-i of 23 nM. Like cFP, JA-2 inhibited the closely related endopeptidase EC 3.4.24.16 1/20 to 1/30 as potently as it did EP24.15, and did not inhibit the other thermolysin-like endopeptidases angiotensin-converting enzyme, endothelin-converting enzyme and neutral endopeptidase. The biological stability of JA-2 was investigated by incubation with a number of membrane and soluble sheep tissue extracts. In contrast with cFP, JA-2 remained intact after 48 h of incubation with all tissues examined. Further modifications to the JA-2 compound failed to improve the potency of this inhibitor. Hence JA-2 is a potent, EP24.15-preferential and biologically stable inhibitor, therefore providing a valuable tool for further assessing the biological functions of EP24.15.

Extraordinary and extensive karyotypic variation: A 48-fold range in chromosome number in the gall-inducing scale insect Apiomorpha (Hemiptera : Coccoidea : Eriococcidae)

Chromosome number reflects strong constraints on karyotype evolution, unescaped by the majority of animal taxa. Although there is commonly chromosomal polymorphism among closely related taxa, very large differences in chromosome number are rare. This study reports one of the most extensive chromosomal ranges yet reported for an animal genus. Apiomorpha Rubsaamen (Hemiptera: Coccoidea: Eriococcidae), an endemic Australian gall-inducing scale insect genus, exhibits an extraordinary 48-fold variation in chromosome number with diploid numbers ranging from 4 to about 192. Diploid complements of all other eriococcids examined to date range only from 6 to 28. Closely related species of Apiomorpha usually have very different karyotypes, to the extent that the variation within some species- groups is as great as that across the entire genus. There is extensive chromosomal variation among populations within 17 of the morphologically defined species of Apiomorpha indicating the existence of cryptic species-complexes. The extent and pattern of karyotypic variation suggests rapid chromosomal evolution via fissions and (or) fusions. It is hypothesized that chromosomal rearrangements in Apiomorpha species may be associated with these insects' tracking the radiation of their speciose host genus, Eucalyptus.

Mechanisms of substitution reactions on cyclometallated platinum(IV) complexes: "Quasi-labile" systems

The substitution reactions of SMe2 by phosphines (PMePh2, PEtPh2, PPh3, P(4-MeC6H4)(3), P(3-MeC6H4)(3), PCy3) on Pt-IV complexes having a cyclometalated imine ligand, two methyl groups in a cis-geometrical arrangement, a halogen, and a dimethyl sulfide as ligands, [Pt(CN)(CH3)(2)(X)(SMe2)], have been studied as a function of temperature, solvent, and electronic and steric characteristics of the phosphines and the X and CN ligands. In all cases, a limiting dissociative mechanism has been found, where the dissociation of the SMe2 ligand corresponds to the rate-determining step. The pentacoordinated species formed behaves as a true pentacoordinated Pt-IV compound in a steady-state concentration, given the solvent independence of the rate constant. The X-ray crystal structures of two of the dimethyl sulfide complexes and a derivative of the pentacoordinate intermediate have been determined. Differences in the individual rate constants for the entrance of the phosphine ligand can only be estimated as reactivity ratios. In all cases an effect of the phosphine size is detected, indicating that an associative step takes place from the pentacoordinated intermediate. The nature of the (CN) imine and X ligands produces differences in the dimethyl sulfide dissociation reactions rates, which can be quantified by the corresponding DeltaS double dagger values (72, 64, 48, 31, and 78 J K-1 mol(-1) for CN/X being C6H4CHNCH2C6H5/Br, C6H4CHNCH2-(2,4,6-(CH3)(3))C6H2/Br, C6H4CHNCH2C6H5/Cl, C6Cl4CHNCH2C6H5/Cl, and C6W4CH2NCHC6H5/ Pr, respectively). As a whole, the donor character of the coordinated C-aromatic and X atoms have the greatest influence on the dissociativeness of the rate-determining step.

Effects of alkalis, oxidants and urea on the nutritive value of rhodes grass (Chloris gayana cv. Callide)

Two in sacco experiments were conducted to evaluate the impact on the nutritive value of rhodes grass hay (Chloris gayana cv. Callide) of treatment with alkalis or oxidants. In Experiment 1, three alkalis (Ca(OH)(2), NaOH, CaO) and two oxidants (NaOCl and H2O2) were applied at levels of 0, 20, 40, 60 or 80 g/kg of dry matter (DM). NaOH, Ca(OH)(2) and CaO had negative linear effects (P < 0.05) on the neutral detergent fibre (NDF) content and positive linear effects (P < 0.05) on the 48 h in sacco disappearances of DM, organic matter (OM), NDF and acid detergent fibre (ADF). NaOCl reduced (P < 0.05) NDF content but had no effect (P > 0.05) on the in sacco disappearances. H2O2 had no effect (P > 0.05) on the composition or digestibility of rhodes grass hay. In Experiment 2, effects of urea (0, 20, 40, 60 and 80 g urea/kg DM) and water (250, 500 and 750 g/kg DM) treatment of rhodes grass hay were examined in a 5 x 3 factorial experiment. Significant interactions between water and urea (P < 0.05) occurred for concentrations of crude protein (CP) and NDF, and 48 h in sacco disappearances of DM, OM (OMD) and NDE The combinations of water (g/kg DM) and urea (g/kg DM) that resulted in the highest concentrations of CP (281 g/kg DM) and OMD (747 g/kg DM) were 250 + 80 and 500 + 80, respectively. NaOH, Ca(OH)(2), CaO and urea significantly alter the NDF content and digestibility of rhodes grass hay, and urea also increases its CP content. Overall, NaOH was the most efficacious, followed by Ca(OH)(2), CaO, urea, NaOCl and H2O2. Crown Copyright (C) 2002 Published by Elsevier Science B.V. All rights reserved.

Program sustainability of a community-based intervention to prevent falls among older Australians

Multi-strategy interventions have been demonstrated to prevent falls among older people, but studies have not explored their sustainability. This paper investigates program sustainability of Stay on Your Feet (SOYF), an Australian multi-strategy falls prevention program (1992-1996) that achieved a significant reduction in falls-related hospital admissions. A series of surveys assessed recall, involvement and current falls prevention activities, 5 years post-SOYF in multiple original SOYF stakeholder groups within the study area [general practitioners (GPs), pharmacists, community health (CH) staff shire councils (SCs) and access committees (ACs)]. Focus groups explored possible behavioural changes in the target group. Surveys were mailed, except to CH staff and ACs. who participated in guided group sessions and were contacted via the telephone, respectively. Response rates were: GPs. 67% (139/209); pharmacists, 79% (53/67); CH staff, 63% (129/204); SCs, 90% (9/10); ACs, 80% (8/10). There were 73 older people in eight focus groups. Of 117 GPs who were practising during SOYF 80% recalled SOYF and 74% of these reported an influence on their practice. Of 46 pharmacists operating a business during SOYF, 45% had heard of SOYF and 79% of these reported being 'somewhat' influenced. Of 76 community health staff (59%) in the area at that time, 99% had heard of SOYF and 82% reported involvement. Four SCs retained a SOYF resource, but none thought current activities were related. Seven ACs reported involvement, but no activities were sustained. Thirty-five focus group participants (48%) remembered SOYF and reported a variety of SOYF-initiated behaviour changes. Program sustainability was clearly demonstrated among health practitioners. Further research is required to assess long-term effect sustainability.