title: Antineoplastic agents. 278. Isolation and structure of axinastatins 2 and 3 from a western Caroline Island marine sponge.
abstract: The Republic of Palau marine sponge Axinella sp. was found to be an exceptionally productive source of cell growth inhibitory substances. The strongly antineoplastic polyether macrocyclic lactones halichondrin B (1) and homohalichondrin B (2) were isolated in 1.2 x 10(-6)% and 5.4 x 10(-7)% yields, respectively. In addition to axinastatin 1 (3), two new and cytostatic (GI50 values of 0.35 to 0.0072 microgram/mL against six human cancer cell lines) cycloheptapeptides designated axinastatins 2 (4) and 3 (5) were discovered in 1.4 x 10(-6)% and 1.25 x 10(-6)% yields. Structures were elucidated by high-resolution FABMS and tandem MS/MS techniques augmented by high-field (400 and 500 MHz) 2D-NMR spectral analyses. The absolute configurations were established by a combination of hydrolysis, derivatization, and chiral gas chromatographic methods.
authors.affiliation: Cancer Research Institute, Arizona State University, Tempe 85287-1604.
authors.forename: G R
authors.initials: GR
authors.lastname: Pettit
authors.forename: F
authors.initials: F
authors.lastname: Gao
authors.forename: R L
authors.initials: RL
authors.lastname: Cerny
authors.forename: D L
authors.initials: DL
authors.lastname: Doubek
authors.forename: L P
authors.initials: LP
authors.lastname: Tackett
authors.forename: J M
authors.initials: JM
authors.lastname: Schmidt
authors.forename: J C
authors.initials: JC
authors.lastname: Chapuis
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000302:isolation & purification*; D003110:Colonic Neoplasms / Q000188:drug therapy; D005260:Female; D006801:Humans; D007938:Leukemia / Q000188:drug therapy; D008175:Lung Neoplasms / Q000188:drug therapy; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D008969:Molecular Sequence Data; D015394:Molecular Structure; D010051:Ovarian Neoplasms / Q000188:drug therapy; D010456:Peptides, Cyclic / Q000737:chemistry / Q000302:isolation & purification* / Q000627:therapeutic use; D011161:Porifera / Q000737:chemistry*; D016339:Spectrometry, Mass, Fast Atom Bombardment; D014407:Tumor Cells, Cultured
chemical_list: D000970:Antineoplastic Agents; D010456:Peptides, Cyclic; C086904:axinastatin 2; C086905:axinastatin 3