Chemical reduction of the radiosensitizer misonidazole by zinc or glucose

Abstract

Misonidazole, 1-(2-nitroimidazol-1-yl)-3-methoxypropan-2-ol, was reduced by zinc dust or glucose in almost neutral or alkaline solutions. T.l.c. of the reduction mixtures has revealed the presence of several products. Two of them have been identified as the azo and the azoxy derivatives of misonidazole. When the reduction was carried out in alkaline solution, another reaction, competitive with the reduction, was observed. This reaction, involving the loss of the nitro group, led to two products, the former deriving from a nucleophilic substitution by OH^– and the latter from an intramolecular displacement. This kind of denitrative process must be considered when the reduction of misonidazole is performed at basic pH. In such conditions two other reduction products have been identified and a possible reaction mechanism for their formation is suggested.