Cyclopropane-containing polyamine analogues are efficient growth inhibitors of a human prostate tumor xenograft in nude mice

Polyamine analogues 7, 10, 18, 27, and 32 containing cyclopropane rings were obtained by chemical synthesis. Their antineoplastic activities were assessed against the cultured human prostate tumor cell lines DU-145, DuPro, and PC-3. Decamines 32 and 27 exhibited variable levels of cytotoxicity against all three cell lines, while 7, 10, and 18 were efficacious against DU-145 and DuPro. Maximum tolerated doses (MTD) for all five compounds in a NCr-nu mouse model were determined at dosing schedules of q1d × 5 (ip) in two cycles with a break of 10 days between cycles. Their antitumor efficacies were then tested against DU-145 tumor xenografts in mice treated with all five agents at their respective MTDs. In addition, the efficacies of 7 and 10 against the same tumor xenograft were assessed at doses below their respective MTDs. In all experiments, administration began two weeks after tumor implantation. All compounds efficiently inhibited tumor growth for up to 50 days postimplantation, with negligible animal ...