Koshikamide B, a cytotoxic peptide lactone from a marine sponge Theonella sp.
Koshikamide B (1) has been isolated from two separate collections of the marine sponge Theonella sp. as the major cytotoxic constituent. Koshikamide B is a 17-residue peptide lactone composed of six proteinogenic amino acids, two D-isomers of proteinogenic amino acids, seven N-methylated amino acids, and two unusual amino acid residues. The unusual amino acids are N(delta)-carbamoylasparagine and 2-(3-amino-2-hydroxy-5-oxopyrrolidin-2-yl)propionic acid (AHPP); the former is first found as the constituent of peptides, whereas the latter is a new amino acid residue. The N-terminus of koshikamide B is blocked by a methoxyacetyl group. The structure of koshikamide B (1) has been determined by interpretation of spectral data and analysis of chemical degradation products. Koshikamide B (1) exhibits cytotoxicity against P388 murine leukemia cells and the human colon tumor (HCT-116) cell line with an IC50 value of 0.45 and 7.5 microg/mL, respectively.
Araki
Takahiro
T
Laboratory of Aquatic Natural Products Chemistry, Graduate School of Agricultural and Life Sciences, The University of Tokyo, Bunkyo-ku, Tokyo 113-8657, Japan.
Matsunaga
Shigeki
S
Nakao
Yoichi
Y
Furihata
Kazuo
K
West
Lyndon
L
Faulkner
D John
DJ
Fusetani
Nobuhiro
N
D000818:Animals; D001216:Asparagine / Q000031:analogs & derivatives / Q000737:chemistry; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D020128:Inhibitory Concentration 50; D007783:Lactones / Q000737:chemistry; D051379:Mice; D009842:Oligopeptides / Q000737:chemistry* / Q000633:toxicity*; D011422:Propionates / Q000737:chemistry; D011759:Pyrrolidines / Q000737:chemistry; D047232:Theonella / Q000737:chemistry* / Q000378:metabolism; D014407:Tumor Cells, Cultured
C534355:2-(3-amino-2-hydroxy-5-oxopyrrolidin-2-yl)propionic acid; D007783:Lactones; C534354:N(delta)-carbamoylasparagine; D009842:Oligopeptides; D011422:Propionates; D011759:Pyrrolidines; C534353:koshikamide B; D001216:Asparagine