N4-(omega-aminoalkyl)-1-[(omega-aminoalkyl)amino]-4-acridinecarboxamides: Novel, potent, cytotoxic, and DNA-binding agents

A series of DNA-binding potential antitumor agents, (omega -aminoalkyl)-4-a cridinecarboxamides, has been prepared either by reduction:of the correspon ding (omega -aminoalkyl)-9-oxo-9,10-dihydro-4-acridinecarboxamides with alu minum amalgam or by aminolysis of the corresponding (omega -aminoalkyl)-1-c hloro -4-acridinecarboxamides with the suitable amine. The noncovalent DNA- binding properties of these compounds have been examined using a fluorometr ic technique. In vitro cytotoxic potencies of these derivatives toward six tumor cell lines, including human colon adenocarcinoma (HT29) and human ova rian-carcinoma (A2780-sensitive, A2780cisR cisplatin-resistant, CH1-sensiti ve, CH1cisR cisplatin-resistant, and SKOV-3) cells, are described and compa red to that of reference drugs.:One highly DNA affinic analogue (3a) has be en identified with a; useful broad spectrum of cytotoxic activity in the 4- 7 nM range (mean IC50 of 6 nM).