Antimicrobial activity of carbazole derivatives

Summary Glycozoline and girinimbine isomers (IV andVII) were synthesized and their activity against 2 bacterial strains, viz.E. coli andS. aureus, and 2 fungal strains, viz.C. albicans andA. niger were studied. The hydroxy synthons (III) were also tested. The authors are thankful to Dr B.N. Apte, Association of Microbiologists of India, Bombay Unit, for providing some of the organisms, to Prof. A.K. De, Indian Institute of Technology, for financial assistance, to Prof. G. D. Shah, Department of Chemistry, Indian Institute of Technology for guidance, encouragement and helpful discussions.     

Staurosporine aglycone (K252-c) and arcyriaflavin A from the marine ascidian,Eudistoma sp

Staurosporine aglycone (K252-c) (compound1) and arcyriaflavin A (2) were isolated from a specimen of the marine ascidian,Eudistoma sp., collected off the coast of West Africa. In addition to expressing micromolar and submicromolar inhibition of enzyme activity against seven protein kinase C isoenzymes and inhibition of proliferation of the human lung cancer A549 and P388 murine leukemia cell lines,1 also inhibited cell adhesion of the EL-4.IL-2 cell line and expressed activity in the K562 bleb and neutrophil assays.     

A new 9,11-secosterol,stellettasterol from a marine spongeStelletta sp

A new 9,11-secosteroid, stellettasterol (1) was isolated from a Japanese marine sponge,Stelletta sp.; its structure was determined by spectroscopic analysis. All NMR signals of1 were unambiguously assigned by application of various 2D NMR techniques. Stellettasterol exhibited antifungal activity againstMortieralla ramannianus.Part 62 of the Bioactive Marine Metabolites series. Part 61: Fusetani, N., Takahashi, M., and Matsunaga, S., Tetrahedron, in press.     

Two new kaempferol 3,7-diglycosides and kaempferitrin in the fernAsplenium trichomanes

Summary The fronds of the fernAsplenium trichomanes contain kaempferol 3,7-dirhamnoside (1) and the new compounds kaempferol 3-O-a-rhamnoside-7-O-a-arabinoside (2) and kaempferol 3-O-a-arabinoside-7-O-a-rhamnoside (3). The presence of the above flavonoids has been shown by spectroscopic methods and chemical degradations.Acknowledgments. The author thanks Prof. H. Wagner (Institut für pharmazeutische Arzneimittellehre der Universität München, München) for a sample of kaempferol 3,7-dirhamnoside, Dr K. R. Markham (Chemistry Division, D.S.I.R., Petone, New Zealand) for a gift of pectinase and Mr A. D'Urso (Botanic Institute, University of Catania) for help in acquiring the plant material.     

1,1-Dimethyl-5,6-dihydroxyindolinium chloride from a deep water marine sponge,Dercitus sp.

Summary 1,1-Dimethyl-5,6-dihydroxyindolinium chloride (1a)was identified from a deep water sample of the marine sponge,Dercitus sp., and its structure was elucidated by spectral methods.Acknowledgments. This is Harbor Branch Oceanographic Institution, Inc., SeaPharm Project Contribution No. 612. We thank Drs K. Rinehart, Jr, S. Pomponi and E. Armstrong for sponge collection.     

Oxytoxins,bioactive molecules produced by the marine opisthobranch molluscOxynoe olivacea from a diet-derived precursor

Summary The ethereal extract of the mucous secretion from the opisthobranch molluscOxynoe olivacea was examined and found to contain two novel ichthyotoxic compounds, named oxytoxin 1 and 2 (1, 2). The structures of1 and2 are closely related to the metabolites previously isolated from the algaCaulerpa prolifera. The activity of the most stable compound was studied in order to investigate the possibility, of a further biological role for these metabolites, which represent an uncommon example of bioactive molecules produced in vivo from a dietary precursor.     

Antitumor activity of the isodon diterpenoids: Structural requirements for the activity

Summary A significant antitumor activity of oridonin (1) and lasiokaurin (2), the kaurene-type diterpenoids ofIsodon species, was shown by their i.p. injection to the test mice inoculated by Ehrlich ascites carcinoma. Enmein (8), compounds9 and3 were also active under larger dose. Subsequently, the relationship between their chemical structure and antitumor activity was investigated, and the activity of oridonin (1) and lasiokaurin (2) was rationalized in terms of their structural feature.     

3,5-Dibromo-2′-chloro-4′-isothiocyanatosalicylanilide,a potent anthelminitic

Summary The compound, 3,5-dibromo-2-chloro-4-isothiocyanatosalicylanilide, has been tested against various nematode and cestode parasites in experimental and domestric animals. It shoved 100% activity againstAncylostoma ceylanicum, A. tubaeformis, Syphacia obvelata, Ascaridia galli, Toxocara spp.,Toxascaris sp.,Gnathostoma spinigerum, Hymenolepis nana, Raillietina spp. andTaenia spp. in doses 25–70 mg/kg given in single or multiple administrations.Acknowledgments. We express sincere thanks to Dr Nitya Nand, F.N.A., CDRI, Lucknow, for his keen interest in the work, to Dr B. N. Dhawan, F.N.A. for providing informations about general pharmacology of the compound, and to Dr R. K. Chatterjee and Dr P. K. Murthy for carrying out antifilarial sreening. Technical assistance of Mr S. C. Bhar and Mr S. Ram is acknowledged.     

Luffolide,a novel anti-inflammatory terpene from the spongeLuffariella sp.

Summary Luffolide (4) is a minor metabolite of the spongeLuffariella sp. from Palau. The structure of luffolide was determined by single crystal X-ray analysis. Luffolide is relatively unstable and undergoes a complex cyclization reaction to give the hexacyclic products5 and6. Luffolide (4) has some of the anti-inflammatory properties of manoalide (1): this may help to define the chemical reaction between manoalide (1) and phospholipase A₂.All crystallographic calculations were done on a PRIME 9950 computer operated by the Cornell Chemistry Computing Facility. Principal programs employed were: FOBS, a data reduction program by G.D. Van Duyne, Cornell University, 1987; MULTAN 80, and RANTAN 80, systems of computer programs for the automatic solution of crystal structures from X-ray diffraction data (locally modified to perform all Fourier calculations including Patterson syntheses) written by P. Main, S. E. Hull, L. Lessinger, G. Germain, J. P. Declercq and M. M. Woolfson, University of York, England, 1980 BDLS, an, anisotropic block diagonal least squares refinement written by K. Hirotsu, E. Arnold, and G. D. Van Duyne, Cornell University, 1987; PLUTO 78, a locally modified crystallographic illustration program by W. D. S. Motherwell, Cambridge Crystallographic Data Centre, 1978; and BOND, a program to calculate molecular parameters and prepare tables written by K. Hirotsu and G. Van Duyne, Cornell University, 1985.Acknowledgment. We thank the Government of the Republic of Palau for a scientific research permit. We thank Dr Klaus Rützler, Smithsonian Institution, Washington, D.C. for identifying the sponge and Mary Kay Harper for performing additional bioassays. This research was supported by grants from the Sea Grant College Programs of California [Projects R/MP-30 to DJF) and R/MP-31 (to RSJ)] and New York (to JC) and the National Institutes of Health (CA 24487 to JC).     

A potent attractant of zoospores ofAphanomyces cochlioides isolated from its host,Spinacia oleracea

A highly potent attractant of zoospores ofAphanomyces cochlioides, a causal fungus of the root rot disease of spinach (Spinacia oleracea), was isolated from spinach roots, and its structure was determined by spectroscopic evidence and chemical synthesis as cochliophilin A (5-hydroxy-6,7-methylenedioxyflavone,1). A chromosorb particle prepared by soaking in solution of1 showed a potent attracting activity toward the zoospores using concentrations of1 above 10^–9 or 10^–10 M.     

Circadian rhythmicity in phosphorylase activity and glycogen content in the heart muscle of the scorpion,Heterometrus fulvipes,C.L. Koch

Summary Maximal activity levels of phosphorylase A and AB at 20.00 h alternate with minimal levels at 08.00 h of the day, while the glycogen content exhibited a reverse trend in the heart of the scorpion,Heterometrus fulvipes.Acknowledgment. The authors thank Prof. K.S. Swami, for providing facilities. The financial assistance rendered by UGC (to VJ) and ICMR (to DCR) is gratefully acknowledged.     

Effect of seasonal variations and cold acclimation on serum transaminase activity of common Indian frogRana tigrina

Summary A definite seasonal change is observed in 2 transaminases, SGOT and SGPT ofR. tigrina. Cold acclimation significantly depresses transaminase activity of serum.Acknowledgments. Thanks are due to Dr M.M. Goil and Dr R. K. Sharma for their invaluable help in various ways. Dr K. Singh would also like to thank S.C.S.T., U.P., for the financial assistance.     

Two derivatives of farnesylacetone from the brown algaCystophora moniliformis

Summary Farnesylacetone epoxide (3) and the isomeric diketone (4) have been isolated from the brown algaCystophora moniliformis.Acknowledgment. We thank Dr K. Noack for CD measurements and interpretations and Mr K. Harada for algal identification.     

Research Articles¶Naturally occurring 2′-O-methylpurine nucleosides with hypotensive properties

2′-O-Methylinosine (1) has been isolated for the first time and shown to be an intrinsic hypotensive principle. Its probable in vivo precursor, 2′-O-methyladenosine (3), showed stronger and even orally potent hypotensive activity. Resistance of the methyladenosine (3) against adenosine deaminase is thought to contribute to its long-lasting activity. The effect of both nucleosides (1 and 3) was not accompanied with any significant change in heart rate, which is often observed with adenosine. Received 2 October 1997; accepted 28 October 1997     

Antimutagenic unusual amino acids from plants

Summary Five unusual amino acids were identified as antimutagens against spontaneous mutation ofSalmonella typhimurium TA100: L-azetidine-2-carboxylic acid (1) from Liliaceae plants, -(methylenecyclopropyl)glycine (2) fromLitchi chinensis seeds, and 2-amino-4-methylhex-5-ynoic acid (3), hypoglycin A (4), and (2S, 4R)-2-amino-4-hydroxyhept-6-ynoic acid (5) fromEuphoria longana seeds. The absolute stereochemistry of5 was determined by its chiral synthesis from L-allylglycine, proving that5 is the C-4 epimer of the amino acid previously isolated from dried longan seeds.This work was partly supported by a Grant-in-Aid form the Ministry of Education, Science, and Culture, Japan, No. 57740283 (to HK).     

Isometachromin,a new cytotoxic sesquiterpenoid from a deep water sponge of the family Spongiidae

Isometachromin (1), a new sesquiterpene-quinone that is related structurally to metachromin C (2), and the known compounds ilimaquinone (3) and and 5-epi-ilimaquinone (4), were isolated from a deep water sponge in the family Spongiidae; the structure of isometachromin was elucidated by spectral methods. Isometachromin exhibits in vitro cytotoxicity against the human lung cancer cell line A 549 (IC₅₀=2.6 g/ml), but not against P 388 murine leukemia (IC₅₀10 g/ml) and also exhibits antimicrobial activity.This research is Harbor Branch Oceanographic Institution (HBOI) contribution number 911. We thank Drs S. A. Pomponi and M. Kelly-Borges (HBOI) for sponge taxonomy, and Dr P. McCarthy and T. Peterson (HBOI) for antimicrobial data.     

Novel synthesis of 2,4-diphenylpyrimido [4,5-b] quinoline

Summary Reaction of n-butyllithium in ether with 2-ethoxyquinoline and further reaction with benzonitrile gives 2,4-diphenylpyrimido [4,5-b] quinoline (I). With the use of lithium di-isopropylamide, compoundI is obtained in better yield without side products.We thank Prof. N. S. Narasimhan and Prof. V. K. Phansalkar for their interest in this work. We are also grateful to the Alexander von Humboldt Foundation, West Germany, and Walcot Gibbs Foundation, U.S.A.     

Ceralbol,a new sesterterpenic alcohol isolated from insect wax

Summary The isolation and structural elucidation of ceralbol (1), a new sesterterpene from the insect waxCeroplastes albolineatus are reported.Contribution No. 465 from Instituto de Quimica de la Universidad Nacional Autonoma de Mexico.This work was supported by a grant from Syntex laboratories, S.A., Mexico, D.F.     

Preparation of optically pure juvenile hormone I labelled in the ester methyl group with tritium at very high specific activity

Summary Radiolabelled juvenile hormone I (3) was prepared in an optically pure form by an enzymatic method using the capacity of accessory sex gland homogenates from maleHyalophora cecropia to transfer the methyl group of S-adenosyl-L-methionine to the carboxylic acid function of the (10R, 11S)-enantiomer of racemic presursor2; the specific activity of3 is higher than 53 Ci/mmole (1.96 TBq/mmole).We are indebted to Dr W. Thelfer, Philadelphia, for providing us with diapausing pupae of male Cecropia silk moths, and to Dipl.-Biol. G. Klages, Darmstadt, for preparing racemic JH-Iacid. Financial support by the Deutsche Forschungsgemeinschaft (grant No. Em 14/8) is gratefully acknowledged.     

Structure and stereochemistry of attenuol,a new lignan fromKnema attenuata (Wall.) Warb.

Summary A new lignan attenuol has been isolated from the bark ofKnema attenuata (Wall.) Warb. Its structure (I) is deduced on the basis of analytical and spectral data. The compound has been assigned the absolute configuration as 2S,3R-dimethyl-1S-(p-hydroxyphenyl)-6,7-methylenedioxytetralin (III).Contribution No. 487 from the Ciba-Geigy Research Centre.Acknowledgments. We thank Dr H. Fuhrer and Dr P. Moser of Ciba-Geigy Ltd. Basle for the NMR spectral data and ORD determinations and Dr S. Selvavinayakam and his colleagues for the analytical results.