Syntheses and properties of 1-methyl-3-phenylaminobenzimidazolium salts, models of DNA adducts of N7-arylaminodeoxyguanosinium salt

When arylaminating carcinogens are administered to cells, they mainly gener ate the C8-arylamino-2'-deoxyguanosine adduct in DNA. A mechanism for this was proposed in which N7-arylaminated 2'-deoxyguanosine acts as an intermed iate; however, it remained unclear whether this is actually the case. To el ucidate the mechanisms involved in the generation of this adduct, a series of 5-substituted 1-methylbenzimidazole derivatives were used as models of t he imidazole moiety of 2'-deoxyguanosine. Syntheses of a series of 5-substi tuted (CH3, H, F, CF3, or NO2) 1-methyl-3-phenylaminobenzimidazolium salts (7) and their related compounds were carried out, and the chemical characte ristics of these products were examined. Keating compound 7 at 80 degreesC for 48 h in H2O/MeOH provided 5-substituted 1-methyl-2-oxo-2,3-dihydrobenzi midazoles but only when this compound contained a CF3 or NO2 substituent. C ompound 7 decomposed in alkaline media, and its rate of decomposition incre ased when this compound had a stronger electron-withdrawing substituent. Th e product obtained under these conditions was 4-substituted N-1-methyl-2-ph enylazoaniline. On the other hand, when 1-methyl-3-(4-nitrophenylamino)benz imidazolium salt was treated under the same conditions as described above, it generated, a demethylated product, 1-(4-nitrophenylamino)benzimidazole, when heated in H2O/MeOH and N-1-formyl-N-1-methyl-2-phenylazoaniline when t reated in alkaline media. When the chemical characteristics of 3-phenylamin o and 3-amino groups were compared using 3-substituted 1-methyl-5-(trifluor omethyl)benzimidazole the 3-phenylamino derivative was found to be more rea ctive.