Specific inhibition of human leukocyte elastase by substituted alpha-pyrones

Several a-pyrones have been synthesized and investigated for their in vitro inhibitory activity using a-chymotrypsin (a-CT), porcine pancreatic elastase (PPE) and human leukocyte elastase (HLE). 4-Hydroxy-6-undecyl-2H-pyran-2-one 4, 4-Hydroxy-6-[(1-butyl)heptyl]-2H-pyran-2-one 5 and 4-Methoxy-6-[(1-butyl) heptyl]-2H-pyran-2-one 6 were found to be specific inhibitors of HLE. These compounds constitute a promising new class of HLE inhibitors.     

Erythropoietic effects of PGE2 and 2 endoperoxide analogs

Summary The erythropoietic effects in exhypoxic polycythemic mice of two endoperoxide analogs were assessed and compared with PGE₂. The 9a, 11a epoxymethano analog (U-44069) was found to be a much more potent erythropoietic stimulus than the 11a,9a analog (U-46619) or PGE₂.This work was supported by a Senior Research Grant-in-Aid from the American Heart Association-Louisiana (DMG) and USPHS Grant No. AM 13211 (JWF).     

Transformation of progesterone byCaldariella acidophila,an extreme thermophilic bacterium

Summary Caldariella Acidophila, a thermophilic bacterium, converts porgesterone (1) to pregn-4-en-3,6,20-trione (2), 5a-pregnan-3, 6, 20-trione (3), pregn-4-en-20a-ol-3-one (4), pregn-4-6-ol-3, 20-dione (5) and pregn-4-en-6a-ol-3, 20-dione (6). Different patterns of these metabolites were obtained by modifying the incubation conditions and using differently treated biocatalysis.     

A simple synthesis of (E)-3-formylbut-2-enenitrile,and its use as a precursor of isotope-labelled zeatin and (±) dihydrozeatin

Summary (E)-3-Formylbut-2-enenitrile (4) is synthesized in 2 steps by reacting pyruvaldehyde dimethylacetal and acetonitrile in the presence of sodium methoxide, followed by acid hydrolysis to give 58% overall yield on distillation. The aldehyde4 can be stepwise and selectively reduced to (E)-3-hydroxymethylbut-2-enylamine (7a) in 37% total yield or exhaustivelyb reduced in 1 step to (±)-4-hydroxy-3-methylbutylamine (6) in 46% total yield. Compound7a and6 can be condensed with 6-chloropurine to give zeatin and (±)dihydrozeatin respectively. This provides a readily accessible method for isotope-labelled zeatin and its derivatives at side chain.Contribution No. 1064, Alberta Research CouncilProcess for the Preparation oftrans-3-formylbut-2-enenitrile S. Chen and J. MacTaggart, patent applicatioin registered in Canada and the United States of America.Acknowledgment. The author thanks Mr J. M. MacTaggart and Mrs C. M. Goulet for valuable experimental assistance and Dr R. M. Elofson for helpful discussions.     

Cannabiripsol: A novelCannabis constituent

Summary Cannabiripsol [(–)(6aR, 9S, 10S, 10aR)9,10-dihydroxy-hexahydrocannabinol] (1), a new cannabinoid was isolated from a South African Cannabis variant. The structure was determined by spectral means and by synthesis.Acknowledgments. This work was supported by contract HSM-42-70-103 from the National Institute on Drug Abuse and by the Research Institute of Pharmaceutical Sciences, University of Mississippi, University, MS 38677. —Cannabis Herbarium specimens are stored in the Herbarium, Department of Pharmacognosy, School of Pharmacy, University of Mississippi.To whom inquiries should be addressed.     

Furan fatty acid steryl esters from the marine spongeDictyonella incisa which show inflammatory activity

Summary Three new furan fatty acids, (9Z, 19Z)-3, 6-epoxyhexacosa-3,5,19-tetraenoic acid (1a), (8Z, 11Z, 14Z, 17Z)-3, 6-epoxyeicosa-3,5,8,11,14,17-hexaenoic acid (2a), and (8Z, 11Z, 14Z, 17E)-3, 6-epoxyeicosa-3,5,8,11,14,17-hexaenoic acid (3a), and a new polyunsaturated fatty acid (5Z, 8Z, 11Z, 14Z, 17E)-eicosa-5,8,11,14,17-pentaenoic acid (6a), present in the spongeDictyonella incisa as the respective steryl esters, have been isolated as methyl esters and their structures have been determined by spectral and chemical analysis. The furan fatty acid esters have shown a high inflammatory activity, which suggests their potential role as feeding deterrents.     

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.     

6H-anthra[1,9-bc]thiophene derivatives from a bryozoan,Dakaira subovoidea

Separation of a lipophilic extract of the bryozoan,Dakaira subovoidea, a common fouling organism of underwater structures, guided by inhibition of lipid peroxide formation in rat liver microsomes, gave 5,7-dihydroxy-1-hydroxymethyl-6-oxo-6H-anthra[1,9-bc]thiophene (1a) and its 1-methoxycarbonyl derivative (1c), together with the known 1,8-dihydroxyanthraquinone (2). The structures were determined by spectral and crystallographic analyses.     

The deamino derivatives of [4-threonine]-oxytocin and [4-threonine]-mesotocin; Analogs possessing a surprising spectrum of diminished pharmacological activities

Zusammenfassung Synthese (Merrifield-Methode) und pharmakologische Eigenschaften der Desamino-Derivate von (4-Threonin)-Oxytocin und (4-Threonin)-Mesoxytocin werden beschrieben.

---

---

This work was supported in part by the Medical College of Ohio, a Contract (No. 69-2193) from the Center for Population Research of the National Institute of Child Health and Human Development, Research Grants from the National Science Foundation (No. GB-4932), the National Institute of Arthritis and Metabolic Diseases (No. AM-01940) and a General Research Support Grant to Columbia University from the National Institutes of Health. The authors wish to thank Mrs.Sara Crumm for performing the amino acid analyses and Mrs.Margot Acosta for performing the bioassays. An abstract of part of this work was presented at the 2nd American Peptide Symposium, Cleveland, Ohio, August 1970;M. Manning andW. H. Sawyer,Peptides (Ed.Saul Lande, Gordon and Breach, New York 1971), in press.     

New C26 delta-lactones from the Dufour's gland of the urticating ant Tetramorium aculeatum.

(6R*)-[(2S*)-2-hydroxyheneicos-12-enyl]-5,6-dihydro-2H-pyran-2-one (1) degree is the major constituent of the secretion of freshly dissected Dufour's gland of the urticating ant Tetramorium 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) degrees 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.     

The relationship between cell division and cell specialization in the mouse intestinal epithelium

Zusammenfassung Der Zusammenhang zwischen der Teilung von Ursprungszellen und der Differenzierung ihrer Tochterzellen wurde anhand von Epithelzellen des Duodenums weisser Mäuser untersucht. Um den Zustand des «steady state» zu erhalten, finden die folgenden Arten von Teilung der Ursprungszellen statt: 1) zwei neue Ursprungszellen; 2) zwei differenzierte Tochterzellen; oder 3) eine neue Ursprungszelle und eine differenzierte Tochterzelle.

---

---

I wish to particularly thank Mrs. Z.Trirogoff for her skilled technical assistance. This work was supported in part by Research Grant No. GM 14749-01, National Institutes of Health and General Research Support Funds, UCLA School of Medicine. Portions of this work were presented before the American Association of Anatomists, Anat. Rec.157, 333 (1967).     

Polymorphism in the somatic chromosomes ofNeotoma micropus Baird,the plains woodrat

Zusammenfassung Die somatischen Chromosomen von 100 Ratten (Wildfänge),Neotoma micropus Baird (Cricetidae), zeigen ein nicht-Robertsonsches polymorphes System mit 2 verschiedenen homologen Chromosomenpaaren. Sie stellen 4 verschiedene Rattenpopulationen mit Polymorphismus dar.

---

---

Supported in part by an American Philosophical Society Grant from the Penrose Fund and a Texas Tech University Faculty Grant.     

Enantiomeric cannabinoids: stereospecificity of psychotropic activity

Summary The 1,1-dimethylheptyl homolog of (–)-(3R,4R)-7-hydroxy-delta-6-tetrahydrocannabinol (compoundII) is highly psychotropic in mice, rats and pigeons. The (+)-(3S,4S) enantiomer (III) was found to be psychotropically inactive at doses up to several thousand times those of the ED₅₀ of (II).We thank Dr A. Breuer and Mrs H. Amsalem for help with the syntheses. The research reported above was supported in Tucson by NIH grant NS 15441; in Uppsala by grants from the Swedish Medical Research Council (5757) and the Swedish Council for the Planning and Coordination of Research (84/2082); in Jerusalem by the Szold Foundation.Presented in part at a meeting at the US National Institute on Drug Abuse, Washington, D.C., October 1986, see NIDA Research Monographs79 (1987) 15.     

1-(Substituted)benzyl-5-aminoimidazole-4-carboxamides are potent orally active inhibitors ofTrypanosoma cruzi in mice

Summary 1-(Substituted)benzyl-5-aminoimidazole-4-carboxamides are potent orally active inhibitors ofTrypanosoma cruzi infections in mice. The most active compounds are the 1-(4-chlorobenzyl)- and 1-(3,4-dichlorobenzyl)-analogs (L-153,094 [2] and L-153,153 [4], resp.) which are approximately 7-fold more potent upon oral administration than nifurtimox (Lampit) in suppressing parasite levels in the blood of mice with acuteTrypanosoma cruzi infections.     

Synthesis of dehydroneotenone

Zusammenfassung Aus 6-Hydroxy-5-(2-methoxy-4,5-methylendioxyphenylacetyl)-2, 3-dihydrobenzo [b] furan (IV) wurde nachVenkataraman Dihydrofurano-isoflavon (V) hergestellt und zu Dehydroneotenon (III) dehydriert.

---

---

Presented in part at the IUPAC Symposium on the Chemistry of Natural Products, Kyoto (Japan), April 1964.     

sRNA methylase activity of embryonic liver

Résumé Utilisant SAM-¹⁴CH₃ il a été démontré que le foie foetal a plus d'activité de sRNA methylase que le foie adulte.

---

---

This investigation was supported in part by an allocation from a Public Health Service General Research Support Grant No. SO 1 FR-05545-03, and an American Cancer Society Grant No. IN 19F to The Jackson Laboratory, Bar Harbor, Maine, and by Public Health Service Research Grants No. HD-01496 from the National Institute of Child Health and Human Development and No. FR-00251 from the Division of Research Facilities and Resources.     

Biotransformation of the flavonoid tiliroside to 7-methylether tiliroside: bioactivity of this metabolite and of its acetylated derivative

Incubation of kaempferol-3-O-β-D-(6"-E-p-coumaroyl)-glucopyranoside (tiliroside) (1) with Aspergillus nidulans gives the 7-methyl ether of tiliroside (2) which is a new compound. Its structure is determined by spectroscopic methods. Cytotoxic studies of 2 and of its acetylated derivative 2a were carried out in vitro against fourteen human leukemic cell lines. Results clearly show that compound 2 is ineffective against all leukemic cell lines tested. On the contrary, compound 2a exhibited cytotoxic activity against four of the cell lines (HL60, DAUDI, HUT78 and MOLT3) and additionally, a dose- and time-dependent effect on DNA synthesis. Received 18 February 1997; received after revision 8 April 1997; accepted 6 May 1997     

Structure revision and cytotoxicity of the germacranolide,stizolicin, fromStizolophus balsamitus (Asteraceae)

Summary The structure of the cytotoxic sesquiterpene lactone, stizolicin, reisolated fromStizolophus balsamitus (Centaurea b.) was revised to atrans, trans germacranolide (1) on the basis of simultaneous application of lanthanide shift reagent and NOE in the NMR.The authors acknowledge the use of the Purdue University Biomedical Magnetic Resonance Laboratory (NIH grant No. RR01077). Support of contract No. N01-CM-97296 and Grant No. CA-33326 from the National Cancer Institute, HHS is gratefully acknowledged. This is paper 18 in the series Potential Antitumor Agents.     

2-Amino-6-[(1'R,2'S)-1',2'-dihydroxypropyl]-3-methyl-pterin-4-one,a biologically active metabolite from the anthozoanAstroides calycularis Pallas

Summary 2-Amino-6-[(1'R,2'S)-1',2'-dihydroxypropyl]-3-methyl-pterin-4-one (1) has been isolated from the marine anthozoanAstroides calycularis; its structure was illustrated by spectral analyses including 2D-NMR and by partial synthesis.1 appears to possess cell-growth inhibiting activity.29 December 1986Work supported by C.N.R. (Progetto Finalizzato Chimica Fine e Secondaria) and by Ministero Pubblica Istruzione Italy. — Acknowledgments. Mass spectral data were provided by Servizio di Spettrometria di massa del C.N.R. e dell'Università di Napoli. The assistance of the staff is gratefully appreciated. Finally we would like to thank Prof. C. Pietropaolo for supplying chick embryo fibroblasts.     

Studies on the murine L-4946 ascitic leukemia in Swiss albino mice

Zusammenfassung Virologische Untersuchungen einer Mäuseleukämie, die sich durch eine «subzelluläre onkogene Komponente» übertragen lässt.

---

---

This work was supported in part by the Developmental Physiology Training Grant No. NIH T1-HD0054; NIH Training Grant No. 1 T01 AMO-5680-01 DM; General Research Support Grant No. 623; and aided by a grant from the National Foundation — March of Dimes. This research was conducted in facilities accredited by the American Association for Accreditation of Laboratory Animal Care.