King's College London

Since their discovery in Streptomyces bacteria over half a century ago, pyrrolobenzodiazepines (PBDs) have generated significant interest as potential chemotherapeutic agents due to their sequence-selective DNA alkylating capacity. The development of synthetic PBD compounds from their naturally derived bacterial counterparts has enhanced both the potency and safety profiles of PBDs. Interestingly, such modifications of traditional PBD cores have sometimes led to an expansion of the mechanism of action of these compounds from simple DNA alkylation. This review documents one such change in mechanism of action of the PBDs, which has been engineered through chemical modifications of traditional PBD structures: the inhibition of transcription factor activity.