A DNA intercalating alkylating agent

In a programme devoted to the synthesis of new anticancer drugs, we have prepared a series of acridine and benzo[b][1,7]phenanthroline derivatives (in collaboration with Pierre Fabre Medicament Laboratories). Of all the products tested (in vitro and in vivo), the most interesting molecules were the ortho-methylamino-hydroxymethyl derivatives. We have shown that these compounds react by formation of quinone-imine-methide intermediates. These highly reactive species are able to react with nucleophiles. The ortho-methylamino-hydroxymethyl derivatives react with DNA by covalent binding. The ratio was estimated to be one drug for three base pairs.
A detailed study of this type of molecule (in the benzophenanthroline series) was presented at the ECTOC conference.