Malevamide D:  Isolation and Structure Determination of an Isodolastatin H Analogue from the Marine CyanobacteriumSymplocahydnoides

Abstract

Malevamide D (1), a highly cytotoxic peptide ester, and the known compound curacin D (5) were isolated from a Hawaiian sample of Symploca hydnoides. The structure of 1 was elucidated by spectroscopic analysis including NMR and high-resolution MS/MS. Partial stereochemical assignments of 1 were made by chiral HPLC analysis of acid and base hydrolysates. Malevamide D (1) demonstrated toxicity against P-388, A-549, HT-29, and MEL-28 cell lines in the subnanomolar range, while curacin D (5) was weakly cytotoxic. Malevamide D (1) is closely related to isodolastatin H (2), which was previously isolated in low yield from the sea hare Dolabella auricularia. A second Hawaiian sample of S. hydnoides yielded curacin D (5) along with the known dolastatin-10 analogue symplostatin-1 (3).

Cloning, sequencing, and biochemical characterization of the nostocyclopeptide biosynthetic gene cluster: molecular basis for imine macrocyclization

“…PCC 7120 (Black and Wolk, 1994;Kaneko et al, 2001) and N. punctiforme ATCC29133. Furthermore, the reduced C-terminal amino acid residues in aeruginosin 298-A from Microcystis aeruginosa (Murakami et al, 1994) and malevamide D from a Hawaiian Symploca hydnoides (Horgen et al, 2002) imply the involvement of a reductive release mechanism in the formation of the primary alcohol in these cyanobacterial peptides.…”

Filamentous tropical marine cyanobacteria: a rich source of natural products for anticancer drug discovery

“…1) have been reported from various Symploca species (Harrigan et al 1998;Luesch et al 2002c;Horgen et al 2002;Simmons et al 2006;Linington et al 2009;Taori et al 2009). A number of these analogues possess potent cytotoxic activity against various cancer cell lines in the nanomolar range and were shown to interfere with the normal function of microtubules.…”

Thiostrepton selectively targets breast cancer cells through inhibition of forkhead box M1 expression

“…A thiazole ring containing antibiotic, thiostrepton (Fig. 1A), originally isolated from Streptomyces azureus ATCC 149215 (15) has been reported to possess antitumor activities (16). Despite the discovery that in prokaryotic cells thiostrepton is an inhibitor of protein translation through binding to the 23sRNA with L11 ribosomal protein (17), little is known about its mechanism of action, its cellular target(s), and its specificity in eukaryotic cells.…”