Clerodane Diterpenes from the Marine Sponge Raspailia bouryesnaultae Collected in South Brazil.

Cintia Lhullier,Eliane De Oliveira Tabalipa,Louis Sandjo,Fernanda Nienkötter Sardá,Naira Zanchett Schneider,Cláudia Oliveira Simões,Eloir Schenkel,João Carraro

doi:10.3390/md17010057

Cintia Lhullier, Eliane De Oliveira Tabalipa + Show 6 more

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https://doi.org/10.3390/md17010057

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Abstract

The marine sponge Raspailia bouryesnaultae, collected in South Brazil, was selected for detailed investigation considering the results of a screening that pointed to an in vitro antiproliferative effect against non-small cells of human lung cancer (A549) and anti-herpes activity against Herpes Simplex virus type 1 (KOS and 29R strains) of ethanolic extracts. The fractionation and chemical investigation of the sponge’s hexanic fraction led to the isolation and structural elucidation of six clerodane diterpenes. The main component was identified as the already-reported raspailol (1), isolated from a sponge of the same genus collected in New Zealand. The structure of a new diterpene (2) with a rearranged skeleton was established by high-resolution mass spectrometry (HRMS) and 1D and 2D Nuclear magnetic resonance spectroscopy (NMR) experiments, and named here as raspadiene. Furthermore, four diterpenes were elucidated as isomers of clerodane diterpenes previously obtained from plants, namely kerlinic acid (3), kerlinic acid methyl ester (4), annonene (5), and 6-hydroxyannonene (6). They differ in their stereochemistry, since these diterpenes are characterized by a trans ring fusion at the decalin moiety and the relative configuration of the two methyl groups at C-8 and C-9 in a cis relationship (type trans/cis). The Raspailia diterpenes have a cis ring fusion at the decalin moiety, and the two methyl groups at C-8 and C-9 are in a trans relationship (type cis/trans). The isolated compounds were evaluated for their potential antiproliferative effects on human cancer cell line A549, and it was observed that the diterpenes bearing a hydroxyl group at C-6 exhibited moderate cytotoxic activity, with 50% inhibitory concentration (IC50) values lower than 25 μM. The evaluation of the potential anti-herpes activity against Herpes Simplex Virus type 1 (HSV-1, KOS and 29R strains) showed that the more promising results were observed for the new compound 2, since it inhibited HSV-1 (KOS and 29R strains) replication by 83% and 74%, respectively.

Highlights

Sponges are primitive filter-feeders, and about 9000 species have already been described, it is thought that there are more than 20,000 marine sponges
Specimens of sponge Raspailia bouryesnaultae collected in the Coral and Aranhas Islands were extracted by maceration with ethanol
Chemical investigation of the sponge Raspailia bouryesnaultae collected from South Brazil led to the isolation and structural elucidation of raspailol as the main component, previously reported from a sponge of the same genus collected in New Zealand, and a new diterpene with a rearranged skeleton

Summary

Introduction

Sponges (phylum Porifera) are primitive filter-feeders, and about 9000 species have already been described, it is thought that there are more than 20,000 marine sponges. They can produce high levels of cytotoxic compounds, with the majority coming from the secondary metabolism, protecting them against predation, overgrowth by fouling organisms, and/or competition for space [1]. The genus Raspailia contains more than 100 described species. Over forty different secondary metabolites have been reported from Raspailia sponges, belonging to five main families of compounds: Raspailynes, raspailols, asmarines, agminosides, and clerodane diterpenes [6]. The seven compounds isolated in this work, from marine sponge Raspailia bouryesnaultae, belong to the class diterpenes of clerodane type

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