Pyrrolobenzodiazepines as Sequence Selective DNA Binding Agents

The heritability of cancers is usually affected by complex interactions between carcinogens and the host's genome. New aspects of the genetics of cancer pathogenesis, such as DNA methylation, and micro RNAs are increasingly recognized as important events. Chemotherapeutic drugs interfere with cell division in different ways, e.g. with the duplication of DNA or the separation of newly formed chromosomes. Most forms of chemotherapy target rapidly dividing cells and are not specific for cancer cells, although some degree of specificity may come from the inability of many cancer cells to repair DNA damage. Hence, chemotherapy has the potential to harm healthy tissues, especially those tissues that have a high replacement rate (e.g. intestinal lining). These cells usually repair themselves after chemotherapy.[1] DNA has long been considered a favored target for cancer chemotherapeutic agents. Indeed many of the most effective clinical agents, such as alkylating and interactive agents, are DNA interactive. Achieving the desired sequence specificity with DNA-interactive agents is considered to be one of the most formidable hurdles in the development of new agents to achieve therapeutic invention.[2]