A New Antitumor Isoquinoline Alkaloid from the Marine Nudibranch Jorunna funebris
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
References (16)
- et al.
Tetrahedron Lett.
(1979) Tetrahedron Lett.
(1992)- et al.
Tetrahedron Lett.
(1977) - et al.
Experientia
(1980) - et al.
Liebigs Ann. Chem.
(1988) - et al.
J. Am. Chem. Soc.
(1982) - et al.
J. Org. Chem.
(1989) - et al.
J. Org. Chem.
(1990)
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2021, European Journal of Medicinal ChemistryCitation Excerpt :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).