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
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.