Polarographic Reduction and Potential Carcinogenity of Substituted 1,3,5-Triazine Nucleosides

Abstract

The DC polarographic reduction of 11 new 5-azacytidine (5-azaCyd) and 5-azauridine (5-azaUrd) derivatives in strictly anhydrous dimethylformamide (DMF) was investigated. The reduction occurred within one two-electron step for all of the substances except 6-amino-3-(β-D-ribofuranosyl)-1,3,5-triazine-2,4(1H,3H)-dione, which was reduced in two one-electron steps. The 5-azaCyd monomethyl derivatives (6-methyl-5-azaCyd and N4-methyl-5-azaCyd) gave polarographic maxima of the 1st kind. Substitution in position 6 poses a marked hindrance to the reducibility of the nucleoside analogues. The α-lipoic acid test was applied to all the compounds to obtain the potential carcinogenity index (tg α). The highest tg α value, viz. 0.372, was found for 6-methyl-5-azaCyd; this value even exceeds that of 5-azaCyd (0.295), a compound which has been included in the category of substances probably carcinogenic to humans in the WHO classification. For the majority of the remaining compounds, the tg a values do not suggest any significant carcinogenic activity.