New C26 δ-lactones from the Dufour's gland of the urticating antTetramorium aculeatum

(6R^*)-{(2S^*)-2-hydroxyheneicos-12-enyl}-5,6-dihydro-2H-pyran-2-one (1)^o is the major constituent of the secretion of freshly dissected Dufour's gland of the urticating antTetramorium aculeatum. In solution, compound 1 is slowly transformed into (1S^*, 5R^*, 7S^*)-7-(nonadec-10-enyl)-2,6-dioxabicyclo[3.3.1]nonan-3-one (2)^o on standing. The structures of compounds 1 and 2 have been established on the basis of their spectral and chemical properties. Compound 1 could be responsible for the urticating properties of the ant.^o IUPAC numbering.     

Juvenile hormone catabolism inManduca sexta: Homologue selectivity of catabolism and identification of a diol-phosphate conjugate as a major end product

We studied time-dependent metabolism of (10R)-[³H] juvenile hormone (JH) III and (10R, 11S)-[³H]JH I injected intoManduca sexta larvae; the hormones are metabolized to polar metabolites, expecially the JH acid-diol, and an unknown. Products were analyzed using a reversed-phase liquid chromatography assay. (10R)-JH III is metabolized much more rapidly than (10R, 11S)-[³H]JH I, whether injected seperately or as a mixture of hormones. The unknown metabolites of JH I and JH III were identified as phosphate conjugates of JH I and JH III diol by tandem mass spectral analysis of isolated samples. The phosphate conjugate of JH I diol is the principle end product of JH I metabolism.     

A newTrichoplusia ni antennal receptor neuron that responds to attomolar concentrations of a minor pheromone component

Summary A newly discovered third class of sensillum trichodea on the antenna ofTrichoplusia ni contains an olfactory receptor neuron that responds to (Z)-9-tetradecen-1-ol acetate at 1×10^–18 M. The threshold of this neuron is 100–1000 times lower than the thresholds of two previously described pheromone-sensitive neurons that detect (Z)-7-dodecen-1-ol acetate and (Z)-7-tetradecen-1-ol acetate. The sensitivity and selectivity of this receptor neuron is evidence that (Z)-9-tetradecen-1-ol acetate may be important for sexual behavior.     

Zur Stereochemie der Propandioldehydrase-Reaktion

Summary Propanedioldehydrase is shown to convert both (+)-(S)-2-²H-propanediol,3, and (–)-(R)-1-²H₂-propanediol,5, to specimens of deuterated propion-aldehyde, for which the (S)-configuration has been established. Thus, in the propanedioldehydrase reaction migration of hydrogen atoms from C–1 to C–2 always occurs with inversion of configuration.     

Effect of xanthurenic acid on P-450-dependent biotransformation by molting glands in vitro

Incubation of molting glands from the crayfishProcambarus clarkii (Y-organ) and the silkwormBombyx mori (prothoracic gland) with 23,24-[²H₄]-2-deoxyecdysone resulted in the production of deutero-ecdysone; this biotransformation was inhibited in the presence of xanthurenic acid. When the experiments were performed under an¹⁸O₂ atmosphere, the¹⁸O atom was introduced into ecdysone, as confirmed by mass spectrometry. We therefore suggest that xanthurenic acid inhibits P-450-dependent hydroxylation of 2-deoxyecdysone. However, deutero-2-deoxyecdysone was not converted to 3-dehydroecdysone when using Y-organs in vitro, although it is a major product. We therefore conclude that the biosynthetic pathway of ecdysteroids inP. clarkii branches at an early step.     

Structure and activity of corticotrophic peptides: Synthesis and biological activity of two corticotrophic peptides with neutral amino acids in positions 17 and 18

Zusammenfassung [D-Ser¹, Nva^17,18]--Corticotropin-(1-19)-nonadecapeptidamid Xa und [D-Ser¹, Nle^17,18]--Corticotropin-(1-19)-nonadecapeptidamid Xb wurden synthetisiert und ihre biologischen Aktivitäten diskutiert.     

Biological characterization of a new and highly potent synthetic analogue of corticotrophin

Zusammenfassung Ein ACTH-Analogon:d-Ser¹-Nle⁴-(Val-NH₂)²⁵--1-25-Corticotrophin wurde tierexperimentell sowie orientierend humanpharmakologisch untersucht. Das Pentacosapeptid (DW-75) zeigt auf Grund der Substitution von 3 Aminosäuren eine gegenüber Peptiden mit natürlicher Sequenz beachtlich erhöhte ACTH-Aktivität.     

Kinetik der hepatischen Farbstoffaufnahme von Indocyaningrün. Einfluss von Bilirubin und Natriumglykocholat

Summary Kinetics of hepatic uptake of indocyanine green, a dye which is used for evaluation of liver function, were studied in the rat. The results indicate that the relationship between ICG-dose and initial hepatic dye uptake obeys Michaelis-Menten kinetics suggesting an interaction of the dye with a carrier or fixed site in the liver cell. Thus it was possible to calculate maximum ICG-uptake (v _max ) and the Michaelis constant (K _m ) of this transport system from several submaximal values.v _max was 7.65 (6-06-9.65)²² mg per 100 g liver/min and K _m 0.56 (0.31–0.81)²². Under the influence of substances which inhibit the elimination of dyes by the liver the parametersv _max and K _m showed changes which allowed characterization of the type of inhibition. While sodium glycocholate had no influence on maximum hepatic ICG-uptake and the Michaelis constant bilirubin caused a significant increase of K _m to 1.29 (0.68–1.90)²² without significantly changingv _max . These data suggest that bilirubin interferes with hepatic uptake of indocyanine green by competitive inhibition and that uptake of bile acids is dependent on a different mechanism.     

Studies on the metabolic fate of the14C-labeled methyl group of a methylhydrazine derivative in P815 mouse leukemia

Zusammenfassung Neben der bereits beschriebenen teilweisen Oxydation der endständigen N-Methylgruppe von 1-Methyl-¹⁴C-2-p-(isopropylcarbamoyl)benzylhydrazin-Hydrochlorid (MBH) (NSC 77213) in vivo⁵ lassen die hier aufgeführten Resultate auch auf eine Transmethylierung dieser Methylgruppe schliessen.     

Volatiles from clover headHypera meles (Fab.) and alfalfaH. postica (Gyllenhal) weevils: search for pheromones

Summary Volatile fractions of the clover head,Hypera meles (Fab.), and alfalfa,Hypera postica (Gyllenhal), weevils contained three of four boll weevil,Anthonomus grandis (Boh.), pheromone components, (Z)-3,3-dimethylcyclohexane ^1,-ethanol and (Z)- and (E)-3,3-dimethylcyclohexane-^1,-acetaldehyde. Also found were eight oxygenated monoterpenes, previously identified as precursors and intermediates of the boll weevil pheromones.     

Inhibitory action ofγ-aminobutyric acid (GABA) onAscaris muscle

Zusammenfassung Die somatische Muskulatur vonAscaris lumbricoides wird durch-Aminobuttersäure in Konzentrationen von 10^–6-10^–5 M völlig gehemmt. Eine hnliche Hemmung wird durch Piperazin (10^–3 M) erzielt. Beide Substanzen steigern die Cl-Permeabilität der Muskelmembran.

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On leave of absence from the Instituto de Biofísica, Universidade do Brazil, Rio de Janeiro (Brazil).     

Propriétés antiacétylcholinestérasiques du diiodométhylate debis-(diméthylamino-3-phénoxy)-1-3 propane,de ses dérivés phénoliques et des esters carbamiques correspondants

Summary Thein vitro anti-acetylcholinesterase properties ofbis-(dimethylamino-3-phenoxy)-1-3 propane dimethiodide (2842 CT) of two phenolics derivatives (3443 CT and 3116 CT) and of the two corresponding carbamic esters (3152 CT et 3113 CT) have been compared using human red blood corpuscles as enzyme source; under specified conditions, the Cl-50 are respectively 8 × 10^–7 M for 2842 CT, 3.5 × 10^–9 for the two phenolic compounds, and 1.5 × 10^–9 for the carbamic esters. The potencies of these phenols are very close to those of the carbamates, being a bit higher or lower depending on the concentration of the inhibitor and on the time of the readingThe two phenolic compounds, like 2842 CT, react readily with the enzyme contrarily to the carbamic esters which combine slowly. On the other hand the inhibition by the phenolic derivatives is as stable against washing as that by the carbamates. The carbamates, but not the phenols, show the slow displacement phenomenon.Some of these characteristics are compatible with the hypothesis that carbamic compounds could act through liberated phenolic functions but others indicate that carbamic groups have a role of their own.     

Influence of 2-methyl-2-(p-1,2,3,4-tetrahydro-1-naphthylphenoxy)propionic acid on the oxidation of cholesterol by rat liver mitochondria

Zusammenfassung Es wird gezeigt, dass bei männlichen Wistar-Ratten im 3-Wochen-Diätexperiment mit Zusatz von 0,3% 2-Methyl-2-(p-1,2,3,4-Tetrahydro-1-naphthylphenoxy)-Propionsäure (Su-13437) die Oxydation von 26-¹⁴C-Cholesterin zu¹⁴CO₂ durch Lebermitochondrien (bezogen auf mg/N) ähnlich wie bei den Kontrollen war. Bei den Versuchstieren war jedoch bei Abwesenheit von Cytosol im System die Oxydation durch Lebermitochondrien erhöht.

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Acknowledgment. This work was supported, in part, by a grant No. HE-03299 and a Research Career Award No. 4-K6-HE-0734 from the National Heart Institute, N.I.H. We are indebted to Dr. W. I.Taylor, CIBA Pharmaceutical Co., Summit, N.J., for the generous gift of Su-13,437.     

(±)9, 10-dihydroxy-Δ 6a(10a)-tetrahydrocanabinol and (±)8, 9-dihydroxy-Δ 6a(10a)-tetrahydrocannabinol: 2 new cannabinoids fromCannabis sativa L.

Summary The structures of 2 new polyhydroxylated cannabinoids, (±)9, 10-dihydroxy- ^6a(10a)-tetrahydorcannabinol and (±)8, 9-dihydroxy- ^6a(10a)-tetrahydrocannabinol, obtained from a hexane extract of an IndianCannabis variant were determined by spectral means and correlation with cannabinol.Acknowledgments. Supported by contract No. HSM-42-70-109 from the National Institute on Drug Abuse and the Research Institute of Pharmaceutical Sciences, School of Pharmacy, University of Mississippi. The authors are grateful to Mrs Glenda Lewis (Research Institute) for running the gas chromatographic analyses and to Mr C. Versluis (Analytical Chemistry Laboratory, University Of Utrecht, The Netherlands) for recording an element list of both compounds.Cannabis Herbarium specimens are stored in the herbarium, Department of Pharmacology, School of Pharmacy, University of Mississippi, University, MS 38677, USA.     

Targeting O 6-methylguanine-DNA methyltransferase with specific inhibitors as a strategy in cancer therapy

O ⁶-methylguanine-DNA methyltransferase (MGMT) repairs the cancer chemotherapy-relevant DNA adducts, O ⁶-methylguanine and O ⁶-chloroethylguanine, induced by methylating and chloroethylating anticancer drugs, respectively. These adducts are cytotoxic, and given the overwhelming evidence that MGMT is a key factor in resistance, strategies for inactivating MGMT have been pursued. A number of drugs have been shown to inactivate MGMT in cells, human tumour models and cancer patients, and O ⁶-benzylguanine and O ⁶-[4-bromothenyl]guanine have been used in clinical trials. While these agents show no side effects per se, they also inactivate MGMT in normal tissues and hence exacerbate the toxic side effects of the alkylating drugs, requiring dose reduction. This might explain why, in any of the reported trials, the outcome has not been improved by their inclusion. It is, however, anticipated that, with the availability of tumour targeting strategies and hematopoetic stem cell protection, MGMT inactivators hold promise for enhancing the effectiveness of alkylating agent chemotherapy.     

Effects of three synthetic peptides analogous to neurohypophyseal hormones on the excitability of giant neurones ofAchatina fulica Férussac

Summary Deamino-dicarba-(d-d-)oxytocin andd-d-Arg-vasotocin at 10^–4 kg/l showed an excitatory effect on the periodically oxcillating neurone (PON) ofAchatina fulica Férussac.d-d-Arg-vasopressin had no effect.     

Komplex-Stabilität und tuberkulostatische Aktivität einiger 8-Oxychinolinderivate

Summary Based on polarographic viz. spectrophotometric determinations of the stabilities of several Cu⁺⁺- and Co⁺⁺⁺ hydroxyquinolin complexes it has been shown that a correlation exists between the quotient of complex-stabilitiesK _Co ⁺⁺⁺ /K _Cu ⁺⁺ and antitubercular activity (cf. table and graph). This supports the hypothesis that the 8-hydroxyquinolin derivatives and analogues act by competitive antagonism; the Cu⁺⁺-hydroxy-quinolates are able to replace Co in a prosthetic group of Mycobacterium-enzyme with Cu.

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Vorgetragen an der Organisch-Chemischen Konferenz des Vereines ungarischer Chemiker, 27. September 1953.

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III. Mitteilung: Acta chim. Hungarica (im Druck).     

Selective potentiating effects of metal ions on vasopressom

Zusammenfassung Der Effekt von Na⁺-, NH₄ ⁺- und Ca⁺⁺-Ionen auf die Blutdruckaktivität von Arginin-Vasopressom wurde untersucht und mit analogen Experimenten (Val⁵-Angiotensin II-Asp¹--Amid) verglichen. Die Wirkungsweise der Ionen-induzierten Potenzierung von Vasopressin wird diskutiert.

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Supported by USPHS Grant No. AM-13567.

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Abbreviations used are: AVP, arginine-vasopressin; bp, blood pres sure; U, unit;n, number of experiments; , mean value; S.E. standard error;p, level of significance; NS, not significant.     

The endocannabinoid system in rat gliosomes and its role in the modulation of glutamate release

The endocannabinoid system and endocannabinoid receptor-driven modulation of glutamate release were studied in rat brain cortex astroglial gliosomes. These preparations contained the endocannabinoids N-arachidonoylethanolamine (anandamide) and 2-arachidonoylglycerol, as well their major biosynthetic (N-acyl-phosphatidylethanolamines-hydrolyzing-phospholipase D and diacylglycerol-lipase) and catabolic (fatty acid amide-hydrolase and monoacylglycerol-lipase) enzymes. Gliosomes expressed type-1 (CB1R), type-2 (CB2R) cannabinoid, and type-1 vanilloid (TRPV1) receptors, as ascertained by Western blotting and confocal microscopy. Methanandamide, a stable analogue of anandamide acting as CB1R, CB2R, and TRPV1 agonist, stimulated or inhibited the depolarization-evoked gliosomal [³H]d-aspartate release, at lower and higher concentrations, respectively. Experiments with ACEA (arachidonyl-2′-chloroethylamide), JWH133 ((6aR,10aR)-3-(1,1-dimethylbutyl)-6a,7,10,10a-tetrahydro-6,6,9-trimethyl-6H-dibenzo[b,d]-pyran) and capsaicin, selective agonists at CB1R, CB2R and TRPV1, respectively, demonstrated that potentiation of [³H]d-aspartate release was due to CB1R while inhibition to CB2R and TRPV1 engagement. These findings were confirmed by using selective receptor antagonists. Furthermore, CB1R activation caused increase of intracellular IP3 and Ca²⁺ concentration, suggesting an involvement of phospholipase C.     

Strong mutagenic action of a bipyridylium herbicide in a N2-fixing blue-green alga

Summary The herbicide paraquat (1,1-dimethyl-4,4-bipyridylium ion) has been found to exert a growth inhibitory effect on the N₂-fixing blue-green algaNostoc muscorum in nitrogen-free (N₂) and NO ₃ ^– media, without any apparent inhibitory or stimulatory effect on the heterocyst-forming capacity of the organism. With a dose of paraquat permitting about 20 and 50% survival of this alga a reverse mutation (fromhet ⁺ nif ^– auxotrophy tohet ⁺ nif ⁺ prototrophy), a forward mutation (for L-methionine-DL-sulfoximine [MSO]-resistance), and an auxotrophic mutation (for carbon-auxotrophy through methylamine [MA]-resistance) have been obtained. The toxic and mutagenic effects of this agrochemical have been compared with those of the well known mutagen MNNG (N-methyl-N-nitro-N-nitrosoguanidine) and found to be stronger than those of the latter in each case.The author wishes to thank Mr Girish Nath, Lakshami Chemicals Pvt. Ltd., Phatuha (Patna), India, for providing pure samples of the herbicide for the present investigation. The receipt of financial assistance for this work in the form of a Higher Research Associateship Award to the author from the University Grants Commission, Govt. of India, New Delhi-110002 (Grant No. F/16-51/83), is thankfully acknowledged.