Benzo-derivatives of Mutagenic-carcinogenic 2-Aminodipyrido[1,2-a:3',2'-d]imidazole

Benzo-derivatives of mutagenic-carcinogenic 2-aminodipyridol1,Z-a:3'.2'-dlimidazole (Glu-P-2) were synthesized in short steps.The interaction of the compounds with DNA and their mutagenicity were investigated.2-Aminodipyrido[l,2-a:3'.2'-dlimidazoles (Glu-P's) are potent mutagen/carcinogens isolated from a pyrolysate of L-glutamic acid.' Glu-P's bind to DNA in vivo at the position 8 of guanine residues in DNA after metabolic activation.2The chemical modification of DNA with Glu-P's is believed to he responsible for their mutagenic-carcinogenic activity.In the path of the chemical modification of DNA, the intercalation of Glu-P's into DNA base pairs preceding the covalent reaction is one of important Recently, we reported the a y n t h e ~i s , ~ physical interaction (intercalation) with D N A , ~ and mutagenicity of methyl-substituted G ~u -P ' s .~ The molecular shapes of Glu-P-derivatives effect on their intercalative ability and the conformation of the intercalated complex,5 which seem to be important factors determining their mutagenic activity.In this communication, we describe synthesis and interaction with DNA of benzo-derivatives of Glu-P-2, compounds 1, 2 and 1, which are structurally related to intercalative antitumor agents