Tritium labelling of antitumour DNA bis intercalators: synthesis of [3H] ditercalinium

Ditercalinium: 2,2'-[4,4'-bipiperidine-1,1'-bis(ethane-1,2-diyl)] bis(10-methoxy-7H-pyrido[4,3-c] carbazolium) tetramethanesulfonate (NSC 366241) is a potent antitumor DNA bis-intercalator characterized by a new mechanism of action. In order to elucidate its biological action at the cellular level and its pharmacokinetic and metabolic properties, radiolabelled ditercalinium was prepared. In the present paper, we report the synthesis of the 11-bromo-10-methoxy-7H-pyrido [4,3-c] carbazole precursor and its reductive tritiation by exchange with [3H]2. The pyrido[4,3-c]carbazole ring labelled in position 11 is then condensed either with the 1,1'bis (2-chloroethyl)-4,4'-bipiperidine chain to provide tritiated ditercalinium or with the 1-(2-chloroethyl) piperidine chain to yield its monomeric analog. (author)