Novel polyhydroxysterols from the Red Sea marine sponge Lamellodysidea herbacea

doi:10.1016/j.steroids.2005.07.004

Steroids

Volume 70, Issue 14, 15 December 2005, Pages 954-959

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Abstract

Chemical investigation of the dichloromethane extract of the Red Sea marine sponge Lamellodysidea herbacea led to the isolation of four novel polyhydroxysteroids: cholesta-8-en-3β,5α,6α,25-tetrol (1), cholesta-8(14)-en-3β,5α,6α,25-tetrol (2), cholesta-8,24-dien-3β,5α,6α-triol (3), and cholesta-8(14),24-dien-3β,5α,6α-triol (4). Their structures were identified through 1D and 2D NMR studies. Relative stereochemistries were established by analysis of chemical shifts, coupling constants, and NOESY correlations. Compounds 3–4 showed antifungal activity against Candida tropicalis, with an inhibition diameter of 13 and 11 mm at 10 μg/disc, respectively.

Introduction

In the most recent classification of Sponges [1], Lamellodysidea appears as a new genus, split off from Dysidea, because of the consistent presence of an encrusting basal plate and the lack of orientation of the skeleton with respect to the surface. Currently, the genus Lamellodysidea includes the two species herbacea and chlorea. Study of the marine sponge Lamellodysidea chlorea, collected off Australia, yielded the linear peptides dysinosins B-D, that were shown to be potent inhibitors of the blood coagulation cascade serine proteases factor VIIa and thrombin [2]. Previously, dysinosin-A had been isolated as a novel inhibitor of factor VIIa and thrombin from an Australian sponge of a new genus and species in the family Dysideidae [3]. Recent chemical investigations by our group of the dichloromethane extract of the marine sponge Lamellodysidea herbacea (Order Dictyoceratida, Family Dysideidae), collected in the Red Sea, have led to the isolation of seven new polychlorinated pyrrolidinone derivatives, in addition to the known dysidamide, dysidamide B and dysidamide C [4].

In our continuing study on the dichloromethane extract of the marine sponge Lamellodysidea herbacea, we isolated from the polar fractions four novel polyhydroxysterols: cholesta-8-en-3β,5α,6α,25-tetrol (1), cholesta-8(14)-en-3β,5α,6α,25-tetrol (2), cholesta-8,24-dien-3β,5α,6α-triol (3), and cholesta-8(14),24-dien-3β,5α,6α-triol (4).

Marine sponges of the genus Dysidea have already yielded a wide range of polyhydroxysterols [5], [6], [7], [8], [9], [10], [11]. Most of them have been proven to be cytotoxic on different tumor cell lines [4], [5], [6], [7], [8], [9]. More recently, three new polyoxygenated sterols were found to inhibit the binding of [I125] interleukin-8 to the human recombinant IL-8 receptor type A [11].

Compounds 1–4 exhibited no antibacterial activity against both S. aureus and E. coli strains at 100 μg/disc, no cytotoxic activity on KB cells at 5 μg/ml, and no anti-PLA₂ activity up to a concentration of 100 μg/ml. However, compounds 3–4 showed antifungal activity against Candida tropicalis, with an inhibition diameter of 13 and 11 mm at 10 μg/disc, respectively. In contrast, compounds 1–2 remained inactive against C. tropicalis at 100 μg/disc.

Section snippets

General methods

Silica gel column chromatographies were carried out using Kieselgel 60 (230–400 mesh, E. Merck). Fractions were monitored by TLC using aluminium-backed sheets (Si gel 60 F254, 0.25 mm thick). Analytical reversed-phase HPLC (Kromasil RP18 column K2185, 4.6 × 250 mm, MeOH/H₂O) was performed with a L-6200A pump (Merck-Hitachi) equipped with a UV–vis detector (λ = 210 nm) L-4250C (Merck-Hitachi) and a chromato-integrator D-2500 (Merck-Hitachi).

Melting points were determined on a Reichert apparatus and are

Results and discussion

Compound 1, the most abundant and polar compound of the series, was isolated in the form of white needles. The HRCIMS gave a pseudomolecular ion peak at m/z 452.3729 for [M + NH₄]⁺ (observed for C₂₇H₅₀O₄N, Δ −1.1 mmu), indicating the presence of five unsaturations in the molecule. The presence of hydroxyl groups was suggested by a strong absorption at 3316 cm⁻¹ in the IR spectrum. The ¹³C NMR spectrum confirmed the presence of 27 carbons, including one tetrasubstitued double bond (δ 133.7 and δ

Acknowledgements

This work is part of Pierre Sauleau's Thesis, supported by the Legs Prêvost of the MNHN of Paris. The authors thank Alain Blond (MNHN, Paris) and Alexandre Deville (MNHN, Paris) for NMR spectra; Lionel Dubost (MNHN, Paris) and Nicole Morin (ENS, Paris) for MS and HRMS measurements, respectively; G. Gastine (MNHN, Paris) for his assistance in antifungal tests; and Jean Vacelet (Station Marine d’Endoume) for the identification of the marine sponge.

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Steroids

Abstract

Introduction

Section snippets

General methods

Results and discussion

Acknowledgements

References (16)

New polychlorinated pyrrolidinones from the Red Sea marine sponge Lamellodysidea herbacea

Tetrahedron

New cytotoxic steroids from the marine sponge Dysidea fragilis coming from the lagoon of Venice

Steroids

Dysinosins B-D, inhibitors of factor VIIa and thrombin from the Australian sponge Lamellodysidea chlorea

J Nat Prod

Dysinosin A: novel inhibitor of factor VIIa and thrombin from a new genus and species of Australian sponge of the family Dysideidae

J Am Chem Soc

Marine natural products: 9α-11α-epoxycholest-7-ene-3β,5α,6β,19-tetrol-6-acetate from a sponge Dysidea sp

J Org Chem

Isolation and identification of eight polyhydroxylated sterols from the sponge Dysidea etheria

J Org Chem

Three new polyhydroxylated sterols with the 5β-configuration from the sponge Dysidea etheria

J Org Chem

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