Antineoplastic agents. 380. Isolation and X-ray crystal structure determination of isoaaptamine from the Republic of Singapore Hymeniacidon sp. and conversion to the phosphate prodrug hystatin 1.
By use of bioassay (murine P388 lymphocytic leukemia cell line) guided isolation procedures, extracts of the Republic of Singapore marine sponge Hymeniacidon sp. were found to contain demethyloxyaaptamine (1) and aaptamine (3) as prominent cancer cell growth inhibitory constituents accompanied by the trace, albeit more active, component isoaaptamine (4). The isolation, X-ray structure elucidation, and antineoplastic and antimicrobial activities of isoaaptamine (4) have been summarized. Because of instability, isoaaptamine (4) was converted to a stable sodium phosphate prodrug designated hystatin 1 (7).
Pettit
George R
GR
Cancer Research Institute and Department of Chemistry and Biochemistry, Arizona State University, Tempe, Arizona 85287-2404, USA.
Hoffmann
Holger
H
McNulty
James
J
Higgs
Kerianne C
KC
Murphy
Alison
A
Molloy
David J
DJ
Herald
Delbert L
DL
Williams
Michael D
MD
Pettit
Robin K
RK
Doubek
Dennis L
DL
Hooper
John N A
JN
Albright
Leslie
L
Schmidt
Jean M
JM
Chapuis
Jean-Charles
JC
Tackett
Larry P
LP
D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D018360:Crystallography, X-Ray; D004354:Drug Screening Assays, Antitumor; D007941:Leukemia P388; D015394:Molecular Structure; D009287:Naphthyridines / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D009792:Oceans and Seas; D010710:Phosphates; D011161:Porifera / Q000737:chemistry*; D011355:Prodrugs / Q000737:chemistry / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D009287:Naphthyridines; D010710:Phosphates; D011355:Prodrugs; C485042:demethyloxyaaptamine; C485041:hystatin 1; C417553:isoaaptamine; C018279:sodium phosphate