SYNTHESIS AND BIOLOGICAL EVALUATION OF PHENANTHRENE-DERIVED CARBOXAMIDES AS CYTOTOXIC AGENTS

A series of phenanthrene-based tricyclic carboxamides has been synthes ized as angular analogues of the clinical acridine carboxamide DACA, a nd their DNA binding, in vitro cytotoxicities and in vivo antitumour a ctivities have been investigated. The compounds fall into two broad to pological classes, where the carboxamide side chain is appended either to one of the terminal rings or to the central ring. In general, comp ounds of the first class showed stronger DNA binding than those of the second, and were the more potent in vitro cytotoxins. However, they w ere considerably less effective than DACA, both as DNA binders and cyt otoxins. A 1,10-phenanthrolinecarboxamide derivative showed significan t in vivo activity. As a class, these fused angular tricyclic carboxam ides do not show sufficiently interesting activity to warrant further studies.