Design, synthesis and antitumor cytotoxicity of novel bis-benzimidazoles.

A series of novel bis-benzimidazoles, IIa-e, IIIa-e and IVa-g, was designed, synthesized and evaluated for anticancer properties. Certain additional analogs were also designed by introducing the p-quinone moiety, a characteristic feature found in mitomycin C, indolequinones and other examples of bioreductively activated alkylating agents. Structural changes of the bis-benzimidazole nucleus with various leaving groups were investigated for their effects on their pharmacological properties. These compounds were evaluated for their cytotoxicity against human cancer cell lines. The results of the studies indicate that the compounds IIa, IIc, IVa, IVc, IVd and IVg possess significant cytotoxic activities against 22 cell lines in seven cancer panels with GI50 values between <0.01 and 99.5 microM especially in the cases of renal cancer, CNS cancer, colon cancer, melanoma and breast cancer.