Synthesis and Biological Properties of New Benz[h]isoquinoline Derivatives

In order to determine the importance of the pyrrolic nitrogen atom in a series of suitably substituted γ-carbolines derivatives for their cytotoxic and antitumor properties, a series of structurally related benz[h]isoquinolines were synthesized. When compared to the "parent" γ-carbolines, these new compounds showed greatly decreased effects on topoisomerases I and II. Whereas the 8-hydroxylated derivatives retained a significant cytotoxicity, all the new compounds were devoid of antitumor effect in the P388 murine ip-ip system.