Marta S. Maier

Patagonicoside A: a novel antifungal disulfated triterpene glycoside from the sea cucumber Psolus patagonicus

Abstract A new triterpene glycoside, patagonicoside A (1), has been isolated from the sea cucumber Psolus patagonicus and its structure has been elucidated by 1D and 2D NMR (1H-, 13C-, 1H–1H COSY, HETCOR, COLOC and NOESY spectra), FAB-MS and chemical evidence. Compound 1 is a disulfated tetrasaccharide with a new aglycon moiety. Patagonicoside A (1) exhibits considerable antifungal activity against the pathogenic fungus Cladosporium cucumerinum.

Evaluation of the antiviral activity of natural sulfated polyhydroxysteroids and their synthetic derivatives and analogs

Disodium 3beta,21-dihydroxypregn-5-en-20-one disulfate (2), sodium 3beta,21-dihydroxypregn-5-en-20-one 3-sulfate (3), sodium 3beta,21-dihydroxypregn-5-en-20-one 21-sulfate (4), and disodium 3beta,6alpha-dihydroxy-5alpha-pregnan-20-one disulfate (6) have been synthesized and completely characterized for the first time from readily available materials. Sulfation was performed using triethylamine-sulfur trioxide complex in dimethylformamide as the sulfating agent. Selective sulfation of 3beta,21-dihydroxypregn-5-en-20-one rendered sodium 3beta,21-dihydroxypregn-5-en-20-one 3-sulfate (3) as the major compound. The synthetic sulfated steroids as well as natural disulfated polyhydroxysteroids (7-9) isolated by us from the antarctic ophiuroid Astrotoma agassizii and the synthetic derivatives disodium 2beta,3alpha,21-trihydroxy-(20R)-cholesta-5,24-diene 3-acetate, 2,21-disulfate (7a) and 2beta,3alpha,21-trihydroxy-(20R)-cholesta-5,24-diene (7b) were comparatively evaluated for their inhibitory effect on the replication of one DNA (HSV-2) and two RNA (PV-3, JV) viruses. In general, steroids with sulfate groups at C-21 and C-2 or C-3 were the most effective in their inhibitory action against HSV-2 and also proved to be active against PV-3 and JV.

Synthesis and antiviral activity of sulfated and acetylated derivatives of 2β,3α-dihydroxy-5α-cholestane

Abstract Five new steroid sulfates, sodium 2β,3α-dihydroxy-5α-cholestane 3-sulfate (6), sodium 2β,3α-dihydroxy-5α-cholestane 2-sulfate (7), disodium 2β,3α-dihydroxy-5α-cholestane disulfate (8), sodium 3α-acetoxy-2β-hydroxy-5α-cholestane 2-sulfate (12), and sodium 2β-acetoxy-3α-hydroxy-5α-cholestane 3-sulfate (13), have been synthesized starting from 3β-hydroxy-5α-cholestane (1). The synthetic steroids were completely characterized by one-dimensional and two-dimensional NMR and FABMS spectra. Sulfation was performed using triethylamine–sulfur trioxide complex in dimethylformamide as the sulfating agent. The sulfated steroids were comparatively evaluated for their inhibitory effect on the replication of herpes simplex virus type 2 (HSV-2). Compounds 7 and 8 were the most effective in their inhibitory action against HSV-2. The disulfated steroid 8 also proved to be active against DEN-2 and JV.

Two novel glucosylceramides from gonads and body walls of the Patagonian starfish Allostichaster inaequalis.

From the water-insoluble lipid fraction of the chloroform/methanol/water extract of the gonads and body walls of the Patagonian starfish Allostichaster inaequalis, two new glucosylceramides (4 and 7) were isolated together with the known phalluside-1 (1) and two glucosylceramides (2 and 3) previously isolated from the starfish Cosmasterias lurida. The new compounds were characterized as (2S,3R,4E,8E,10E)-1-(β-d-glucopyranosyloxy)-3-hydroxy-2-[(R)-2-hydroxy-15-tetracosenoyl] amino-4,8,10-octadecatriene (4) and (2S,3R,4E,15Z)-1-(β-d-glucopyranosyloxy)-3-hydroxy-2-[(R)-2-hydroxyhexadecanoyl] amino-4,15-docosadiene (7) by means of spectroscopic and chemical methods.

Enzymatic deacetylation of steroids bearing labile functions

Abstract Lipase from Candida cylindracea and Candida antarctica catalyzes the removal of acetyl groups from 3β-acetoxypregn-5-en-20-one and 3β-acetoxy-20-(S)-hydroxycholest-5-en-23-one through a transesterification reaction in organic solvents.

Isolation and structure of glucosylceramides from the starfish Cosmasterias lurida

From the water-insoluble lipid fraction of the methylene chloride/methanol extract of the starfish Cosmasterias lurida, two new glucosylceramides together with a known glucosylceramide, ophidiacerebroside E, were isolated by chromatographic procedures and characterized by spectroscopic (1H and 13C nuclear magnetic resonance, mass spectrometry) methods. The new compounds were identified as (2S, 3R, 4E, 8E, 10E)-1-(β-d-glucopyranosyloxy)-3-hydroxy-2-[(R)-2-hydroxyheptadecanoyl)amino]-9-methyl-4,8,10-octadecatriene (3) and (2S,3R,4E,8E,10E)-1-(β-d-glucopyranosyloxy)-3-hydroxy-2-[(R)-2-hydroxyoctadecanoyl)amino]-9-methyl-4,8,10-octadecatriene (4).

A natural tetranortriterpenoid with immunomodulating properties as a potential anti-HSV agent

Abstract Meliacine (MA), an antiviral principle present in partially purified leaf extracts of Melia azedarach L., prevents the development of herpetic stromal keratitis (HSK) in mice by diminishing the viral load in the eye and the severity of lesions caused by a virus-induced immunopathological reaction. The tetranortriterpenoid 1-cinnamoyl-3,11-dihydroxymeliacarpin (CDM), obtained from MA purification, displays anti-herpetic activity and impedes nuclear factor κB (NF-κB) activation in HSV-1 infected conjunctival cells. To extend our understanding about CDM biological properties, we investigated its anti-HSV-1 activity as well as the effect on NF-κB activation and cytokine secretion induced by viral (HSV-1) and no-viral (LPS) stimuli, in corneal cells and macrophages. CDM exerted a potent anti-HSV-1 effect on corneal cells and inhibited NF-κB translocation to the nucleus, leading to a decrease in IL-6 production. Besides, CDM seemed to modulate IL-6 and TNF-α responses in macrophages, whether they were infected with HSV-1 or stimulated with LPS. However, CDM did not affect NF-κB activation in these cells, suggesting that an alternative NF-κB cell signaling pathway would be involved in the modulation of cytokine production. We conclude that, in addition to its antiviral effect, CDM would be acting as an immunomodulating compound which would be responsible for the improvement of murine HSK already reported.

Biological Activities of Sulfated Glycosides from Echinoderms

Abstract The classes Asteroidea (starfishes) and Holothuroidea (sea cucumbers) belonging to the phylum Echinodermata are characterized by their content in toxic saponins. Asterosaponins from starfishes are sulfated steroidal glycosides whereas holothurins from sea cucumbers are triterpenoid glycosides with sulfate groups attached to the monosaccharide residues in sixty percent of the saponins isolated so far. Starfishes also contain steroidal mono- and diglycosides which occur as complex mixtures with asterosaponins. Due to their toxicity and membranotropic action, these polar compounds have attracted the attention of chemists and pharmacologists and a wide spectrum of biological activities has been found for these saponins. The purpose of this communication is to review the structural characteristics and biological properties of the saponins isolated from starfishes and sea cucumbers in the last five years, focusing on the structural elucidation and evaluation of antifungal, cytotoxic and antiviral properties of some examples of the authors laboratory isolated from starfishes and sea cucumbers collected near the Patagonian shore and Antarctica.

Biologically Active Triterpene Glycosides from Sea Cucumbers (Holothuroidea, Echinodermata)

ABSTRACT: Sea cucumbers are characterized by their content in holothurins, triterpenoid glycosides that are responsible for the toxicity of these echinoderms. Nearly 100 holothurins isolated in the last twenty years are grouped into three main aglycone structural types: 3β-hydroxyholost-9(11)-ene, 3β-hydroxyholost-7-ene and non-holostane based aglycones. This communication offers a general view of the structural characteristics of these saponins and the spectral features in their 1 H-and 13 C-NMRand FAB-MS spectra. Recent advances in the unambiguous spectroscopic characterization of the triterpenoid skeleton, the substitution patterns and the complete structure of the oligosaccharide chain are discussed.

Biosynthesis of the butenolide ring of cardenolides in Digitalis purpurea

Abstract Administration of labelled 3β,20ξ-dihydroxy-23-norchol-5-enoic acid, 3-oxo-20ξ-hydroxy-23-norchol-4-enoic acid, 3β,20ξ-dihydroxy-23-nor-5β-cholanoic acid, 3β,14β,20ξ-trihydroxy-23-nor-5β-cholanoic acid, 3β-hydroxy-23-norchola-5,20(22)E-dienoic acid, 3-oxo-23-norchola-4,20(22)E-dienoic acid and 3β-hydroxy-23-nor-5β-chol-20(22)E-enoic acid to Digitalis purpurea intact plants produced labelled digitoxin and gitoxin. The incorporation results indicate the existence of an alternative pathway, via norcholanoic acid derivatives, for the biosynthesis of the butenolide ring of cardenolides.