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: G R Pettit, F Gao, R L Cerny, D L Doubek, L P Tackett, J M Schmidt, J C Chapuis
• Journal: Journal of medicinal chemistry (J Med Chem) Vol. 37 Issue 8 Pg. 1165-8 (Apr 15 1994) ISSN: 0022-2623 [Print] United States
• PMID: 8164258 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S., Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Antineoplastic Agents
• Peptides, Cyclic
• axinastatin 2
• axinastatin 3

Topics

• Amino Acid Sequence
• Animals
• Antineoplastic Agents (chemistry, isolation & purification)
• Colonic Neoplasms (drug therapy)
• Female
• Humans
• Leukemia (drug therapy)
• Lung Neoplasms (drug therapy)
• Magnetic Resonance Spectroscopy
• Mass Spectrometry
• Molecular Sequence Data
• Molecular Structure
• Ovarian Neoplasms (drug therapy)
• Peptides, Cyclic (chemistry, isolation & purification, therapeutic use)
• Porifera (chemistry)
• Spectrometry, Mass, Fast Atom Bombardment
• Tumor Cells, Cultured