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Ova preliminarna studija procenjuje toksičnost i bezbednost dva biljna sastojka Souroubea spp Botanical Blend (SSBB) i Platanus Tree Bark (PTB) nakon oralne primene kod pasa u povišenim dozama u trajanju od 28 dana. Biljne mešavine SSBB i PTB su dva glavna aktivna sastojka u Sin Susto™, novog prirodnog proizvoda registrovanog za preventivu/smanjenje anksioznosti kod pasa. Tri zdrave ženke pasa su primale povišene doze SSBB, PTB ili placebo nakon čega je praćena pojava sistemskih ili lokalnih neželjenih efekata. Podaci iz ovog preliminarnog istraživanja su pokazali da SSBB i PTB nisu izazvali nikakve neželjene efekte kod pasa i mogu se smatrati bezbednim što je omogućilo dalje istraživanje i izvođenje kontrolisanih ispitivanja u cilju demonstriranja bezbednosti i toksičnosti preparata Sin Susto™ kod pasa.

The Marcgraviaceae is a neotropical plant family of lianas and shrubs distributed throughout Central and South America, mainly in evergreen and semi-evergreen tropical forests. In this study, extracts of 12 Marcgraviaceae species were assessed for inhibition of bacterial quorum sensing (QS) in Chromobacterium violaceum, bacterial biofilm formation in Pseudomonas aeruginosa PA14, and fungal growth in Saccharomyces cerevisiae. Six species showed promising inhibitory activities in at least one of the three bioassays (Marcgravia nervosa Triana & Planch., Marcgravia polyantha Delp., Marcgravia schippii Standl., Marcgraviastrum subsessile (Benth.) Bedell, Schwartzia brasiliensis (Choisy) Bedell ex Gir-Canas, and Schwartzia costaricensis (Gilg.) Bedell). Analyses of the crude extract of the leaves of Marcgravia nervosa using HPLC-APCI-MS showed the presence of five pentacyclic triterpenes: ursolic acid (2), betulinic acid (3), [alpha]-amyrin (4), [beta]-amyrin (5), lupeol (6). Bioassay-guided fractionation of this plant resulted in the isolation and identification of 2-methoxy-1,4-naphthoquinone (1) as the active principle with a minimum inhibitory concentration (MIC) of 85-100 [micro]mol x [L.sup.-1] against Saccharomyces cerevisiae BY4741 (haploid) and BY4743 (diploid). Key words: Marcgraviaceae, Marcgravia nervosa, quorum sensing, biofilm, antifungal, naphthoquinone. Les Marcgraviaceae constituent une famille neotropicale de lianes et d'arbustes distribuee a travers l'Amerique Centrale et l'Amerique du Sud, principalement dans les forets tropicales sempervirentes et semi-sempervirentes. Dans cette etude, des extraits de 12 especes de Marcgraviaceae ont ete evalues quant a leur activite inhibitrice de detection de quorum (DQ) bacterien chez Chromobacterium violaceum, de la formation de biofilm chez Pseudomonas aeruginosa PA14 et de la croissance fongique chez Saccharomyces cerevisiae. Six especes ont montre des activites inhibitrices prometteuses dans au moins un des trois essais biologiques (Marcgravia nervosa Triana & Planch., Marcgravia polyantha Delp., Marcgravia schippii Standl., Marcgraviastrum subsessile (Benth.) Bedell, Schwartzia brasiliensis (Choisy) Bedell ex Gir-Canas et Schwartzia costaricensis (Gilg.) Bedell). Des analyses d'extraits bruts de feuilles de Marcgravia nervosa par HPLC-APCI-MS ont montre la presence de cinq triterpenes pentacycliques : l'acide ursolique (2), l'acide betulinique (3), l'[alpha]-amyrine (4), la [beta]-amyrine (5) et le lupeol (6). Le fractionnement de cette plante guide par les essais biologiques a resulte en l'isolement et l'identification de la 2-methoxy-1,4-naphthoquinone (1) comme principe actif possedant une concentration inhibitrice minimale (CIM) de 85-100 [micro]mol x [L.sup.-1] envers Saccharomyces cerevisiae BY4741 (haploide) et BY4743 (diploide). [Traduit par la Redaction] Mots-cles : Marcgraviaceae, Marcgravia nervosa, detection de quorum, biofilm, antifongique, naphthoquinone., Introduction The Marcgraviaceae is a neotropical plant family of lianas and shrubs consisting of seven genera and 130 species distributed throughout Central and South America, mainly in evergreen and semi-evergreen [...]

The mode of action of the anxiolytic medicinal plant Souroubea sympetala was investigated to test the hypothesis that extracts and the active principle act at the pharmacologically important [GABA.SUB.A]-benzodiazepine ([GABA.sub.A]-BZD) receptor. Leaf extracts prepared by ethyl acetate extraction or supercritical extraction, previously determined to have 5.54 mg/g and 6.78 mg/g of the active principle, betulinic acid, respectively, reduced behavioural parameters associated with anxiety in a rat model. When animals were pretreated with the [GABA.sub.A]-BZD receptor antagonist flumazenil, followed by the plant extracts, or a more soluble derivative of the active principle, the methyl ester of betulinic acid (MeBA), flumazenil eliminated the anxiety- reducing effect of plant extracts and MeBA, demonstrating that S. sympetala acts via an agonist action on the [GABA.sub.A]-BZD receptor. An in vitro [GABA.sub.A]-BZD competitive receptor binding assay also demonstrated that S. sympetala extracts have an affinity for the [GABA.sub.A]-BZD receptor, with an [EC.sub.50] value of 123 p.g/mL (EtOAc leaf extract) and 154 µg/mL (supercritical CO2 extract). These experiments indicate that S. sympetala acts at the [GABA.sub.A]-BZD receptor to elicit anxiolysis. Key words: natural health product, anxiety, pharmacology, betulinic acid, methyl ester of betulinic acid. Le mode d'action de la plante medicinale anxiolytique Souroubea sympetala a ete etudie afin de verifier l'hypothese que les extraits et le principe actif de la plante agissent sur le recepteur [GABA.SUB.A]-benzodiazepine ([GABA.sub.A]-BZD), un recepteur d'importance clinique. Des extraits de feuilles prepares par extraction a l'acetate d'ethyle ou par extraction supercritique, dont on a determine qu'ils contenaient respectivement 5,54 mg/g et 6,78 mg/g de principe actif, l'acide betulinique, reduisaient les parametres comportementaux associes a l'anxiete chez le rat utilise comme modele. Lorsque les animaux etaient pretraites avec un antagoniste du recepteur [GABA.sub.A]-BZD, le flumazenil, et des extraits de la plante ou d'un derive plus soluble du principe actif, l'ester de methyle de l'acide betulinique (MeBA), le flumazenil eliminait l'effet anxiolytique des extraits de la plante, demontrant ainsi que S. sympetala agit par une action agoniste du recepteur [GABA.sub.A]-BZD. Un test de competition de liaison du recepteur [GABA.sub.A]-BZD realise in vitro a aussi demontre que les extraits de S. sympetala ont une affinite pour le recepteur [GABA.sub.A]-BZD, avec des valeurs de [EC.sub.50] de 123 pg/mL (extrait de feuilles a l'acetate d'ethyle) et 154 pg/mL (extrait supercritique au C[O.sub.2]). Ces experiences indiquent que S. sympetala agit sur le recepteur [GABA.sub.A]-BZD pour provoquer un effet anxiolytique. [Traduit par la Redaction] Mots-cles: produit de sante naturel, anxiete, pharmacologie, acide betulinique, ester de methyle d'acide betulinique., Introduction The major neurotransmitter implicated in the etiology of anxiety disorders is 7-amino butyric acid (GABA) (Treiman 2001; Lydiard 2003). GABA is the major inhibitory neurotransmitter in the central nervous [...]

The reaction of benzynes, generated from halobenzenes with lithium tetramethylpipiperide (LTMP) at-40 to-78 [degrees]C, with ketone enolates affords benzocyclobutenols in fair to good yields. Key words: benzyne, ketone enolates, anthracenes, benzocyclobutenol, alkoxides.

The syntheses of trichiliasterone A (3[Beta]-hydroxypregnan-2,16-dione) and trichiliasterone B (2-hydroxyandrost1,4-diene-3,16-dione) have been carried out starting from isoandrosterone and testosterone acetate, respectively. In each synthesis the functionality in the D ring was installed prior to working on ring A. In the case of trichiliasterone A, the D ring chemistry involved a Wittig reaction to generate the 17-methylene group, followed by Se[O.sub.2] oxidation to give an [alpha],[beta]-unsaturated ketone. Reaction with lithium dimethyl cuprate gave the required 17-ethyl-16-keto functionality. A 2,3-epoxy enol acetate served as the key intermediate for the generation of the 2-keto-3-hydroxy functions in ring A. The transposition of the keto function from C-16 to C-17 in the synthesis of trichiliasterone B was accomplished via oxymercurationdemercuration of the [[Delta].sup.16-17] double bond followed by oxidation. The hydroxyl group at C-2 and the additional ring A unsaturation were introduced by lead tetra-acetate treatment of the 3-keto-4-enone function and subsequent air oxidation. Key words: 16-ketosteroids, plant steroids, Trichilia hirta, trichiliasterones.

Three syntheses of the natural synergist dillapiol from the natural, commercially available sesamol as starting material, are described. A major difference between these is the order of introduction of the additional methoxy and allyl substituents. In one of the syntheses, a formyl group is introduced at C4 via an electrophilic aromatic substitution reaction and then converted into the methoxy group using a Baeyer--Villiger reaction and subsequent methylation; in the other two, a directed ortho-metalation, Baeyer--Viniger, methylation sequence was employed. Various intermediates along the synthetic route were used to generate more than 30 analogs, including the 4-thiomethyldillapiol, to investigate the structure activity relationships of the pesticide synergism of these compounds. Radio-labeled dillapiol, bearing [sup.14]C at the C4 methoxy group was also prepared. Initial screening with mosquito larvae showed that most of the derivatives prepared in this study had signifacant synergistic activities in combination with the phototoxic larvicide [alpha]-therthiophene. Key words: dillapiol, insecticide synergists, dillapiol analogs, 4-methylthiodillapiol.

A study concerning the synthesis of N-protected optically active alpha-amino esters is analyzed. Results provide applications and mechanistic aspects.

The isolation of six CD-spiro-triterpenoids from the bark extract of Ruptiliocarpon caracolito and their characterization are presented. The structure of the spirocaracolitones A-F was examined by a combination of proton and carbon N

Heat induced decomposition of group of monoalcoholic derivatives of 2-benzylidenebenzocyclobutene was analyzed. The rate of ring opening for these derivatives is usually faster than that of the ketone form. Electrocyclization reactions were observed for the various intermediate vinylallenes. The cyclization pattern is dependent on the substituent at carbon 1. Phenyl or vinyl substituents promoted the formation of benzylideneanthrone and benzylidene tetralones. On the other hand, alkynylphenyl substituents promoted the generation of three other products.

The reaction of (R)-pantolactone esters of racemic alpha-bromo acids (4) with primary amines in THF at room temperature had been found to produce alpha-amino esters in a highly diastereomeric manner in more than 50% yield. The application of the same conditions to the reaction of 4 with R = CH2alkyl or aryl, with dibenzylamine in THF containing 20 mol % of tetra-n-butylammonium iodide resulted in the formation of (S,R)-alpha-amino esters.

Research has been conducted on antioxidants. The authors describe the synthesis of these compounds and their design strategy.

Objectives: A novel anxiolytic natural health product (NHP) containing Souroubea sympetala and Platanus occidentalis is available for the companion animal market and is currently being developed for clinical evaluation. Addressing the risk of potential NHP–drug interactions, this study investigated S. sympetala and P. occidentalis plant extracts, and their identified bioactive compounds, for effects on the activity of cytochrome P450 (CYP) isozymes and the metabolism of the conventional anti‐anxiety medication diazepam. Methods: Souroubea sympetala and P. occidentalis extracts, a 1 : 1 blend of the two extracts, and five triterpenes were tested for inhibitory effects on human recombinant CYP3A4, CYP2D6, CYP2C9 and CYP2C19 activity using a fluorometric plate assay. Direct effects on the metabolism of diazepam were evaluated using human liver microsomes with drug and metabolite quantification by ultra‐high‐pressure liquid chromatography and mass spectroscopy. Key findings: The active substances betulinic acid (BA) and ursolic acid (UA) strongly inhibited CYP3A4 activity while UA and lupeol moderately inhibited CYP2C19. All extracts exhibited strong activity against the tested isozymes at 50–100 μg/ml. BA and all plant extracts blocked the formation of major diazepam metabolites. Conclusions: Betulinic acid, UA and both the extracts and blended product are expected to affect the metabolism of diazepam when given in high dose. [ABSTRACT FROM AUTHOR]