Isolation and Structures of Pipecolidepsins A and B, Cytotoxic Cyclic Depsipeptides from the Madagascan Sponge Homophymia lamellosa

Abstract

Two new cyclic depsipeptides, pipecolidepsins A and B (1 and 2), have been isolated from the sponge Homophymia lamellosa collected off the coast of Madagascar. Their structures were determined by a combination of NMR experiments and by LC-MS analysis of the amino acid fragments obtained by hydrolysis and derivatization using Marfey's reagent. In addition to several common amino acids, these peptides contain unusual residues, including 2-amino-3-hydroxy-4,5-dimethylhexanoic acid, 3-ethoxyasparagine, 3,4-dimethylglutamine, 4,7-diamino-2,3-dihydroxy-7-oxoheptanoic acid, and 3-hydroxyaspartic acid as well as a terminal 3-hydroxy-2,4,6-trimethylheptanoic acid residue. Pipecolidepsins A and B displayed cytotoxic activity against a panel of different human tumor cell lines.

Drugs and Drug Candidates from Marine Sources: An Assessment of the Current “State of Play”

“…The PharmaMar group recently presented data at the 2014 EORTEC meeting that demonstrated activity in these three modified marine-derived compounds (l " Fig. 7) [51,116,117]. Irvalec was pulled from clinical trials by PharmaMar at the Phase II level, so it is interesting that they are now reporting on it and the other two [118].…”

Anticancer potential of bioactive peptides from animal sources

“…Marine sponges are an abundant source of bioactive peptides with anticancer potential. In recent years, most researchers have focused on bioactive cyclic peptides and depsipeptides with highly unique structures that contain a wide variety of unusual amino acids and other building blocks (62)(63)(64).…”

“…Nine cyclodepsipeptides from the sponge Homophymia sp., homophymines B-E and A1-E1, have exhibited very potent cytotoxic activity with IC 50 values in the nM range against a panel of human cancer cell lines (71). Recently, two cyclic depsipeptides isolated from a Madagascan sponge (Homophymia lamellosa), pipecolidepsins A and B (64), have been found to exhibit cytotoxic activity against human lung, colon, and breast cancer cells (64,72).…”

Peptides, Peptidomimetics, and Polypeptides from Marine Sources: A Wealth of Natural Sources for Pharmaceutical Applications

“…The extract was found to be cytotoxic against human cell lines of lung cancer (A-549), colon cancer (HT-29), and breast cancer (MDA-MB-231) because of the presence of these two bioactive peptides [73]. Similarly, an acetonitrile/water extract of the marine sponge Geodia barretti extracted with acetonitrile/water in different ratios led to the discovery of two peptides, barrettides A and B, having two disulfide bonds each.…”