Leptosins, antitumour metabolites of a fungus isolated from a marine alga

Abstract

Leptosins A B, C, D, E and F, chaetocin derivatives, have been isolated from the mycelium of a strain of Leptosphaeria sp. attached to the marine alga Sargassum tortile. Their stereostructures, with a different configuration from that of related compounds, have been elucidated by spectroscopic analyses using various 1 D and 2D NMR techniques and some chemical transformations. All the compounds showed potent cytotoxicity against cultured P388 cells, and leptosins A and C exhibited significant antitumour activity against Sarcoma 180 ascites.' 3C NMR spectra of 1 (Table 1) by distortionless enhancement by polarization transfer (DEPT) and 'H-'H and 'H-13C correlation spectroscopy (COSY) experiments and comparison with spectral data for related compounds revealed signals for two hydroxy methine groups (C-31 and C-11') linked to two quaternary sp3-hybridized carbons, two methines (C-5a and C-5'a) bearing two nitrogens and a quaternary sp3-carbon, four quaternary sp3-carbons (C-3, C-12, C-3' and C-12') each 1 x = 4

Diketopiperazines from Marine Organisms

“…are cytotoxic dimeric derivatives that were obtained from the fungus Leptosphaeria sp. found on the brown alga Sargassum tortile [54]. The structures of 28 -33 were determined by spectroscopic analyses.…”

 

“…In addition, leptosins A and C can inhibit the growth of rat ascites tumor cells effectively, and leptosin M has an important inhibitory effect on topoisomerase II and protein kinase PTK, CaMKIII. [14,15] The structures of bisindole alkaloids (12-45) were shown in Figure 6.…”

Mycochemistry of marine algicolous fungi

“…Furthermore, 242 was evidenced to be a cell cycle inhibitor and exhibited in vivo activity against P388 leukemia and Lewis lung carcinoma cells (Kanoh et al 1997(Kanoh et al , 1999. [262][263][264][265][268][269][270], each featuring two sulfur bridges, exhibited extreme activity against P388 cells with ED 50 values ranging from 0.0023 to 0.0057 μM (Table 6) (Takahashi et al 1994a(Takahashi et al , b, 1995aYamada et al 2002Yamada et al , 2004. In order to explore the cytotoxic mechanism of leptosins, their effect on DNA topoisomerases (topo) I and II and cell apoptosis was investigated.…”

“…Moreover, the metabolites even varied with algal species and locations. Despite the lack of direct evidences, the growth and metabolic specialty of MAFs may correlate with algal constituents and interact with commensal microbes to some extent (Kuwada et al 2006; (Takahashi et al 1994a(Takahashi et al , b, 1995aYamada et al 2002Yamada et al , 2004 No.…”