Benzimidazo[1,2-c]quinazoline dimers as potential antitumor agents

The 6-substituted benzimidazo[1,2-c]quinazoline 1 is a lead structure from our DNA intercalator program and is cytotoxic to the human colon cancer tumor line HT-29 with an inhibitory concentration 50, IC50 of 4.00 mu M. In order to try and improve the limited cytotoxicity of this class of compound we prepared a series consisting of two benzimidazo[1,2-c]quinazoline moieties linked by a polyalkylamino bridge, of different length and substitution. The compound with the -NH-(CH2)(3)-N(CH3)-(CH2)(3)-NH-bridge had an inhibitory concentration 50, IC50 of 0.5 mu M. When tested in vivo, however, no clear antitumor activity was produced in the human breast cancer tumor line MX-1 or the human melanoma tumor line LOX, human tumor xenografts models.