Substituent effects within the DNA binding subunit of CBI analogues of the duocarmycins and CC-1065

A series of CBI analogues of the duocarmycins and CC-1065 exploring substituent effects within the first indole DNA binding subunit are detailed. Substitution at the indole C5 position led to cytotoxic potency enhancements that are ≥1000-fold, providing simplified analogues containing a single DNA binding subunit that are more potent (IC50=2–3 pM) than CBI-TMI, duocarmycin SA, or CC-1065.