Elsevier

Tetrahedron

Volume 56, Issue 37, 8 September 2000, Pages 7305-7308
Tetrahedron

A New Antitumor Isoquinoline Alkaloid from the Marine Nudibranch Jorunna funebris

https://doi.org/10.1016/S0040-4020(00)00629-3Get rights and content

Abstract

A new dimeric isoquinoline alkaloid, jorumycin (3), has been isolated from the skin and the mucus of the Pacific nudibranch Jorunna funebris. The structure has been fully elucidated on the grounds of ESMS data and of an extensive 2D NMR analysis. The cytotoxicity of 3 was evaluated against various human cancer cell lines and was found to be slightly less potent than Et 743 (2).

Introduction

Dimeric isoquinoline alkaloids have been independently isolated from bacteria,1., 2., 3. marine sponges,4., 5., 6. and tunicates.7., 8. These metabolites have often revealed interesting antimicrobial and antitumor activities. The earliest example of this class of compounds has been saframycin C (1), the structure of which was determined by X-ray crystallographic analysis.2 To date other saframycin-like products have been reported, including ecteinascidin 743 (Et 743, 2), one of the most potent marine-derived antitumor agents.9 In this paper we wish to report the isolation and structure elucidation of a new dimeric isoquinoline alkaloid, jorumycin (3), isolated from the mantle and mucus of the Pacific nudibranch Jorunna funebris (Mollusca: Nudibranchia: Doridina: Kentrodorididae). Although less potent than Et 743 (2), jorumycin (3) shares most of the promising antitumor properties.

Section snippets

Results and Discussion

The nudibranch J. funebris was collected in March 1998 together with a blue sponge. The biological material was immediately frozen. The nudibranchs (two specimens) and the mucus released by the animals were extracted with acetone. TLC analysis of these crude extracts indicated the presence of an UV-absorbing (254 nm) product, later characterized as 3, localized in the mantle and the mucus of the molluscs. Although jorumycin (3) was the major constituent of extracts, its isolation and

Conclusions

Jorumycin (3) is a new dimeric isoquinoline related to the ecteinascidins and the saframycins, two well-known classes of promising antitumor and antimicrobial alkaloids. In particular jorumycin (3) shows a molecular structure very similar to that of renieramycin E (7), that has been isolated from the marine sponge Reniera sp. However, a full structure elucidation of 7, as well as a discussion of its biological properties, have never been reported.5 Carbinolamine-containing antibiotics, like Et

General methods

1D and 2D NMR spectra were recorded on Bruker AMX 500 and Bruker AMX 300. The CHCl3 resonances at δ 7.26 and 77.0 were used as an internal reference. MS spectra were obtained by ‘Servizio di Spettrometria di Massa’ of Naples. Infrared spectra were recorded by Bio-Rad FTS-7 FT/IR spectrophotometer. Optical rotations were determined by JASCO DIP-370 polarimeter. HPLC was performed by Waters liquid chromatography apparatus equipped with two 510 pump units.

Biological material

The sponge (Oceanapia sp.) and the mollusc

Acknowledgements

This study is part of a bilateral international project between ICMIB (CNR, Italy) and NIO (India). NMR spectra were recorded at ‘Servizio di NMR dell'Area di Arco Felice’. All NMR staff are acknowledged. We are grateful to Dr P. Ferrante, for the ES MS analysis. Special thanks are due to the ‘Istituto BIOMAR’ and Dr Lola Garcia Gravalos for the biological assays. The authors are very grateful to Dr P. A. Thomas and Dr Ernesto Mollo respectively, for the taxonomic identification and collection

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    The results indicated that renieramycin H had antimicrobial activities against Streptococcus pneumoniae (MIC = 6.25–12.5 μg/disk), Bacillus subtilis (MIC = 12.5–25 μg/disk), Neisseria gonorrheae (MIC = 6.25–12.5 μg/disk), Penicillin-resistant S. pneumoniae (MIC = 50–100 μg/disk), Group A Streptococcus (MIC = 12.5–25 μg/disk) and Penicillin-resistant N. gonorrheae (MIC 1.56–3.12 μg/disk) [24]. Fontana et al. reported that jorumycin possessed a growth-inhibiting activity on a variety of Gram-positive bacteria, such as Staphylococcus aureus and Bacillus subtilis, and no growth-inhibiting effect on Escherichia coli at the concentration less than 50 ng/mL [32]. Antileishmanial activity of renieramycin A was evaluated by using recombinant Leishmania amazonensis expressing enhanced green fluorescent protein (La/egfp).

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