| Abstract
| - 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), neoamphimedineY (5), and neoamphimedine Z (6). A completely new acridine, alpkinidine (7), was also isolated. Adisk 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) ofthe 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 themost selective. The rationale used to characterize the new structures is outlined along with therelated biosynthetic pathways envisioned to generate 2 and 7.
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