Structures and cytotoxic properties of sponge-derived bisannulated acridines.
A reinvestigation of sponge natural products from additional Indo-Pacific collections of Xestospongiacf. carbonaria and X. cf. exigua has provided further insights on the structures, biological activities, and biosynthetic origin of bisannulated acridines. These alkaloids include one known pyridoacridine, neoamphimedine (2), and three new analogues, 5-methoxyneoamphimedine (4), neoamphimedine Y (5), and neoamphimedine Z (6). A completely new acridine, alpkinidine (7), was also isolated. A disk diffusion soft agar assay, using a panel of five cancer cell lines (solid tumors and leukemias) and two normal cells, was used to evaluate the differential cytotoxicity (solid tumor selectivity) of the sponge semipure extracts and selected compounds including amphimedine (1), 2, 4, and 7. While all four compounds were solid tumor selective, 1 and 2 were the most potent and 4 was the most selective. The rationale used to characterize the new structures is outlined along with the related biosynthetic pathways envisioned to generate 2 and 7.
Thale
Zia
Z
Department of Chemistry and Biochemistry, University of California, Santa Cruz, California 95064, USA.
Johnson
Tyler
T
Tenney
Karen
K
Wenzel
Philip J
PJ
Lobkovsky
Emil
E
Clardy
Jon
J
Media
Joe
J
Pietraszkiewicz
Halina
H
Valeriote
Frederick A
FA
Crews
Phillip
P
D000166:Acridines / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D000470:Alkaloids / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D000818:Animals; D004354:Drug Screening Assays, Antitumor; D007214:Indonesia; D015394:Molecular Structure; D019906:Nuclear Magnetic Resonance, Biomolecular; D010219:Papua New Guinea; D011161:Porifera / Q000737:chemistry*; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
D000166:Acridines; D000470:Alkaloids; C474173:neoamphimedine