Several new pyridoacridine alkaloids, dehydrokuanoniamine B (1), shermilamine C 
(2), and cystodytin J (3), in addition to the known compounds cystodytin A (4), 
kuanoniamine D (5), shermilamine B (6), and eilatin (7), were isolated from a 
Fijian Cystodytes sp. ascidian. Their structures were determined by analyses of 
spectroscopic data. These compounds along with a previously reported 
pyridoacridine, diplamine (8), showed dose-dependent inhibition of proliferation 
in human colon tumor (HCT) cells in vitro. All compounds inhibited the 
topoisomerase (TOPO) II-mediated decatenation of kinetoplast DNA (kDNA) in a 
dose-dependent manner. The pyridoacridines' ability to inhibit TOPO II-mediated 
decatenation of kDNA correlated with their cytotoxic potencies and their ability 
to intercalate into calf thymus DNA. These results suggest that disruption of 
the function of TOPO II, subsequent to intercalation, is a probable mechanism by 
which pyridoacridines inhibit the proliferation of HCT cells. Incorporation 
studies show that pyridoacridines disrupt DNA and RNA synthesis with little 
effect on protein synthesis. It appears that DNA is the primary cellular target 
of the pyridoacridine alkaloids. These results are consistent with those for 
known DNA intercalators.