Antineoplastic agents 491. Synthetic conversion of aaptamine to isoaaptamine, 9-demethylaaptamine, and 4-methylaaptamine.
Aaptamine (1) was used as starting material for synthetic transformation to isoaaptamine (2), 9-demethylaaptamine (5), and 4-methylaaptamine (6). A general method for the selective O-demethylation of such 1H-benzo[de][1,6]-naphthyridine (1) marine sponge constituents at position C-9 has been developed. Selective O-demethylation of aaptamine (1) and 1-methylaaptamine (11) with 48% hydrobromic acid led to 9-demethylaaptamine (5) and isoaaptamine (2), respectively. A selection of other aaptamine derivatives were synthesized, and their structures were unambiguously determined by X-ray methods. In addition, their cancer cell growth inhibitory properties were evaluated against the murine P388 lymphocytic cell line and a minipanel of human cancer cell lines. Evaluation as inhibitors of the PKC signal transduction pathway and against a selection of microorganisms was also undertaken. Aaptamine derivatives 3 and 5 had broad-spectrum antimicrobial activities.
Pettit
George R
GR
Cancer Research Institute and Department of Chemistry and Biochemistry, Arizona State University, P.O. Box 872404, Tempe, Arizona 85287-2404, USA.
Hoffmann
Holger
H
Herald
Delbert L
DL
McNulty
James
J
Murphy
Alison
A
Higgs
Kerianne C
KC
Hamel
Ernest
E
Lewin
Nancy E
NE
Pearce
Larry V
LV
Blumberg
Peter M
PM
Pettit
Robin K
RK
Knight
John C
JC
D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D001419:Bacteria / Q000187:drug effects; D002176:Candida albicans / Q000187:drug effects; D003455:Cryptococcus neoformans / Q000187:drug effects; D004354:Drug Screening Assays, Antitumor; D007941:Leukemia P388; D051379:Mice; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D009287:Naphthyridines / Q000138:chemical synthesis* / Q000737:chemistry* / Q000494:pharmacology; D011161:Porifera / Q000737:chemistry; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured
C486054:4-methylaaptamine; C486052:9-demethylaaptamine; D000970:Antineoplastic Agents; D009287:Naphthyridines; C417553:isoaaptamine; C043986:aaptamine