Goniothalamicin and annonacin: Bioactive acetogenins fromGoniothalamus giganteus (Annonaceae)

Summary Using brine shrimp lethality for activity-directed fractionation, goniothalamicin (I), a new tetrahydroxy-mono-tetrahydrofuran fatty acid -lactone (acetogenin), has been isolated from ethanolic extracts of the stem bark ofGoniothalamus giganteus Hook. f., Thomas (Annonaceae). This novel compound was found to be cytotoxic and insecticidal and inhibited the formation of crown gall tumors on potato discs. Annonacin (II), the only other reported mono-tetrahydrofuran acetogenin, was also isolated; the previously reported 9ASK (astrocytoma reversal) activity ofII was confirmed, andII is now also found to be weakly active against 3PS murine leukemia.     

Gigantecin: A novel antimitotic and cytotoxic acetogenin,with nonadjacent tetrahydrofuran rings,fromGoniothalamus giganteus (Annonaceae)

Summary Gigantecin (I), a novel tetrahydroxy-di-tetrahydrofuran fatty acid -lactone (acetogenin), was isolated from an ethanolic extract of the stem bark ofGoniothalamus giganteus Hook. f., Thomas (Annonaceae), by means of activity-directed fractionation (brine shrimp lethality test). This new compound is extremely cytotoxic to human tumor cells, inhibits crown gall tumors on potato discs, and is active in an assay designed to detect antimitotic agents (9 ASK).     

Annonacin, a novel, biologically active polyketide from Annona densicoma

A new linear polyketide, Annonacin (I), has been isolated from active extracts of the stembark of Annona densicoma Mart. Annonacin (I) is highly cytotoxic and is active in an assay designed to detect antimitotic agents. The structure of (I) was determined by analysis of spectroscopic data.     

Anthraquinone pigments from a conidiating mutant ofTrichoderma viride

Summary Two pigments responsible for the yellow-orange color of a brown conidiating mutant of the deuteromyceteTrichoderma viride were isolated and spectroscopically identified as 1,3,6,8-tetrahydroxyanthraquinone (I) and 1-acetyl-2,4,5,7-tetrahydroxy-9,10-anthracenedione (II). Both compounds are known substances but were not yet reported as metabolites of this fungal species. Their relationship to other anthraquinones produced byT. viride is discussed.Dedicated to Dr Z. Vanek, on the occasion of his 60th birthday.Upper case letters denote multiplicity arising from the directly bonded protons, lower case letters that from the geminal and vicinal couplings.     

Sylvaticin: A new cytotoxic and insecticidal acetogenin fromRollinia sylvatica (Annonaceae)

Summary Sylvaticin (I), a new tetrahydroxy annonaceous acetogenin with nonadjacent tetrahydrofuran rings, has been isolated from the dried fruits ofRollinia sylvatica St. Hil. (Annonaceae). This compound is extremely cytotoxic to human tumor cells and shows promising insect control properties.     

Silymarin,an inhibitor of prostaglandin synthetase

Summary Silybin (I), silydianin (II) and silychristin (III), the main constituents of silymarin, inhibit the formation of prostaglandins in vitro. The inhibition is log-linearly dependent on the concentration of the effectors.F. Fiebrich, Thesis, University of Vienna 1977.H. Koch, Dt. ApothZtg118, 1844 (1978); reported in part at the Colloquium Pharmaceuticum in Münster, 21st November 1978.     

Silymarin,an inhibitor of lipoxygenase

Summary Silybin (I), silydianin (II) and, silychristin (III), the main constituents, of silymarin, non-competitively inhibit the lipoxygenase from soybeans (EC 1.13.11.12) in vitro.F. Fiebrich, Thesis, University of Vienna 1977.H. Koch, Dt. ApothZtg118, 1844 (1978); reported in part at the Colloquium Pharmaceuticum in Münster, 21 st November 1978.     

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.     

A non-peroxide norsesterterpene from a marine spongeHyrtios erecta

Summary A new norsesterterpene, hyrtial4, and known sesterterpenes,1–3, have been isolated from an anti-inflammatory active crude extract of the spongeHyrtios erecta.This sponge,Hyrtios (Heteronema) erecta Keller 1889, collected in 1980/81, from Tonga was extremely abundant in the Vava'u Is. Group.We thank Prof. R. Jacobs and his research group at UCSB for this data.     

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.     

Epicatechin can cause the seedling growth inhibitor,nagilactone E,to induce growth stimulation

Summary A possible new role for the flavonoid (–)-epicatechin (II) is described. It has no growth effects on its own, but when it is added to lettuce and rice seeds together with the known seedling growth inhibitor nagilactone E (I), the growth inhibitor activity ofI can cease and growth stimulation can be observed.     

The sperm attractant ofHormosira banksii (Phaeophyceae,Fucales), a seaweed common to Australia and New Zealand

Summary Hormosira banksii is a taxonomically isolated brown seaweed endemic to Australia and New Zealand. The sperm attractant of this species has been isolated and identified as trans-1-vinyl-2-(1E, 3Z-hexadienyl)-cyclopropane (I) (hormosirene).Hormosira is the first organism in which a cyclopropane derivative has been found to act as a hormone in sexual reproduction. The implication of this finding in relation to phylogeny and phytogeography is discussed.Acknowledgment. A substantial part of this work was supported by Deutsche Forschungsgemeinschaft (DFG).     

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.     

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.     

Observations on the toxicity and metabolic relationships of polygodial,the chemical defense of the nudibranchDendrodoris limbata

Summary Polygodial (1), the defense metabolite stored in the skin of the nudibranchDendrodoris limbata, is toxic for the mollusc itself when injected into the hepatopancreas. Biosynthetic experiments using labeled mevalonic acid were devised to investigate a possible metabolic relationship between1 and the mixture of sesquiterpenoidic esters2, stored in the hepatopancreas. The results suggest that1 and2 are biosynthesized by independent pathways.Thanks are due to G. Villani for supplyingDendrodoris limbata and to A. Trabucco for technical assistance.     

The antifertility action ofa-chlorohydrin: Enzyme inhibition bya-chlorohydrin phosphate

Summary Preparations of the enzymes glyceraldehyde-3-phosphate dehydrogenase and triosephosphate isomerase are shown to be inhibited bya-chlorohydrin phosphate (II) in a competitive and non-competitive manner, respectively.a-Chlorohydrin (I), glycidol and epi-chlorohydrin have no inhibitory activities suggesting that their antifertility actions are due to their metabolism in vivo toa-chlorohydrin phosphate.     

Marine antitumor agents: 14-deoxycrassin and pseudoplexaurol,new cembranoid diterpenes from the Caribbean gorgonianPseudoplexaura porosa

Two new cytotoxic antitumor diterpenoids of the cembrane class, named 14-deoxycrassin (3) and pseudoplexaurol (4), have been isolated from the Caribbean gorgonian octocoralPseudoplexaura porosa. The structure of lactone3, possessing the infrequently encountered -methylene--lactone ring, has been established from spectral and chemical data and that of alcohol4 has been established from spectral data.     

Pregnanes from defensive glands of a belostomatid bug

The aquatic bugAbedus herberti (Hemiptera: Belostomatidae) secretes a mixture containing four pregnanes (desoxycorticosterone (I), pregnenolone (II), progesterone (III), and 3-hydroxy-pregn-5-en-20-one (IV)) from its cephalic glands. Pregnanes had previously been characterized from the defensive glands of aquatic beetles (Dytiscidae) and shown to be deterrent to fish. It may be specifically under predation pressure from fish thatA. herberti and Dytiscidae evolved their comparable defenses.     

Luffariellolide,an anti-inflammatory sesterterpene from the marine spongeLuffariella sp.

Summary Luffariellolide (2) is a sesterterpene from the Palauan spongeLuffariella sp. that has useful anti-inflammatory properties. In contrast with the irreversible action of manoalide (1) on phospholipase A₂, luffariellolide (2) is a slightly less potent but partially reversible PLA₂ inhibitor.30 December 1986Acknowledgment We thank Edward Luedtke, Elise Clason and Ellen Snideman for performing some of the assays reported above. The sponge was identified by Dr. Klaus Rützler, Smithsonian Institution, Washington, D.C. The research was supported by grants from Allergan Pharmaceuticals and the California Sea Grant College Program (Projects R/MP-30 and R/MP-31).     

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.