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 diffe rent 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 m u M. When tested in vivo, however, no clear antitumor activity was pro duced in the human breast cancer tumor line MX-1 or the human melanoma tumor line LOX, human tumor xenografts models.