ANTIPROLIFERATIVE ACTIVITY OF SOME UNSUBSTITUTED ANGULAR ANALOGOUES OF ELLIPTICINE

With the aim of obtaining further knowledge on the antiproliferative a ctivity of pyrroloquinolines and isoquinolines, we prepared four unsub stituted angular pyridotetrahydrocarbazoles having a fourth non-aromat ic ring, via modified Fischer synthesis. These compounds may be consid ered as simpler analogues of ellipticine. They induced evident antipro liferative effects in Ehrlich ascites and in CHO cells in vitro, but w ere ineffective on T2 bacteriophage. These compounds formed molecular complexes with DNA in vitro, while in CHO cells in vivo, they induced double-strand breaks in DNA and DNA-protein cross-links. These data su ggest that these ellipticine analogoues are capable of inhibiting topo isomerase II, as the parent compound does. The most active derivative was 2N-5H-6,7,8,9-tetrahydropyrido[2,3-a]carbazole, which represents a n interesting model for the study of new antitumor drugs.