Establishment of substituent effects in the DNA binding subunit of CBI analogues of the duocarmycins and CC-1065

Academic Article
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related to degree

  • Kastrinsky, David, Ph.D. in Synthetic Organic Chemistry, Scripps Research 2000 - 2005

publication date

  • 2003

abstract

  • An extensive series of CBI analogues of the duocarmycins and CC-1065 exploring substituent effects within the first indole DNA binding subunit is detailed. In general, substitution at the indole C5 position led to cytotoxic potency enhancements that can be >/=1000-fold providing simplified analogues containing a single DNA binding subunit that are more potent (IC(50)=2-3 pM) than CBI-TMI, duocarmycin SA, or CC-1065.