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 generate the C8-arylamino-2'-deoxyguanosine adduct in DNA. A mechanism for this was proposed in which N7-arylaminated 2'-deoxyguanosine acts as an intermediate; however, it remained unclear whether this is actually the case. To elucidate the mechanisms involved in the generation of this adduct, a series of 5-substituted 1-methylbenzimidazole derivatives were used as models of the imidazole moiety of 2'-deoxyguanosine. Syntheses of a series of 5-substituted (CH(3), H, F, CF(3), or NO(2)) 1-methyl-3-phenylaminobenzimidazolium salts (7) and their related compounds were carried out, and the chemical characteristics of these products were examined. Heating compound 7 at 80 degrees C for 48 h in H(2)O/MeOH provided 5-substituted 1-methyl-2-oxo-2, 3-dihydrobenzimidazoles but only when this compound contained a CF(3) or NO(2) substituent. Compound 7 decomposed in alkaline media, and its rate of decomposition increased when this compound had a stronger electron-withdrawing substituent. The product obtained under these conditions was 4-substituted N(1)-methyl-2-phenylazoaniline. On the other hand, when 1-methyl-3-(4-nitrophenylamino)benzimidazolium salt was treated under the same conditions as described above, it generated a demethylated product, 1-(4-nitrophenylamino)benzimidazole, when heated in H(2)O/MeOH and N(1)-formyl-N(1)-methyl-2-phenylazoaniline when treated in alkaline media. When the chemical characteristics of 3-phenylamino and 3-amino groups were compared using 3-substituted 1-methyl-5-(trifluoromethyl)benzimidazoles, the 3-phenylamino derivative was found to be more reactive.
Kaiya
T
T
Faculty of Pharmaceutical Sciences, Nagoya City University, Tanabedori, Mizuho-ku, Nagoya 467-8603, Japan.
Fujiwara
T
T
Kohda
K
K
D000588:Amines / Q000138:chemical synthesis / Q000737:chemistry*; D001562:Benzimidazoles / Q000138:chemical synthesis / Q000737:chemistry*; D018736:DNA Adducts / Q000138:chemical synthesis / Q000737:chemistry*; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000138:chemical synthesis / Q000737:chemistry*; D006358:Hot Temperature; D006863:Hydrogen-Ion Concentration; D009682:Magnetic Resonance Spectroscopy; D008956:Models, Chemical
D000588:Amines; D001562:Benzimidazoles; D018736:DNA Adducts; D003849:Deoxyguanosine