Synthesis and in vitro biological evaluation of new polyamine conjugates as potential anticancer drugs

The synthesis of new polyamine derivatives containing dimeric quinoline (3a-c), cinnoline (4a-c) and phthalimide (7a-c and 8a-c) moieties is described. Three different polyamines: (1,4-bis(3-aminopropyl) piperazine (a), 4,9-dioxa-1,12-dodecanediamine (b), 3,3'-diamino-N-methyldipropylamine (c) were used as linkers. The new compounds were obtained according to known procedures. Their biological activity was assessed in vitro in a highly aggressive melanoma cell line A375. Polyamine diimides containing phthalimide moieties demonstrated no inhibitory activities against melanoma cells. Quinoline diamides were more efficient than cinnoline ones. Mainly cytostatic activity exerted as altered cell cycle profiles was observed at the concentrations causing about 50% reduction of adherent cell proliferation. Based on their structure as well as their biological activity, we assume that some of the newly synthesized compounds may act as DNA bisintercalators. This study might be useful for further designing and developing anticancer drugs with potent activities. (C) 2010 Published by Elsevier Masson SAS.