DNA interactive agents have been used in the clinical setting for the treatment
of cancer since the beginning of modern-era chemotherapy. Despite a shift of
focus towards molecular targeted therapy, DNA remains a critical macromolecular
target for anti-cancer intervention and the next generation of agents must conform to
the optimum combination of increased therapeutic activity and reduced off-target toxicity.
We evaluate the potential of non-covalent DNA binding small molecules as
“gene-control” agents, exploiting inherent or engineered sequence selectivity, to target
critical genomic sequences. In addition we review examples of natural products and synthetic derivatives that exert their
activity through sequence specific DNA-covalent modification.
Keywords: Alkylating agents, Anticancer chemotherapeutics, Covalent binding, DNA recognition, DNA-targeting agents,
Non-covalent binding, Polyamides, Sequence specificity.
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