Design, synthesis, and biological evaluation of achiral analogs of duocarmycin SA
Daniell, K.; Stewart, M.; Madsen, E. C.; Le, M.; Handl, H. L.; Brooks, N.; Kiakos, K.; Hartley, J. A.; Lee, M. Design, synthesis, and biological evaluation of achiral analogs of duocarmycin SA. Bioorg. Med. Chem. Lett. 2005, 15, 177-80.
The design, synthesis, as well as biochemical and biological evaluation of two novel achiral analogs of duocarmycin SA (DUMSA), 1 and 2, are described. Like CC-1065 and adozelesin, compounds 1 and 2 covalently reacted with adenine-N3 in AT-rich sequences and led to the formation of DNA strand breaks upon heating. The cytotoxicity of compounds 1 and 2 against human cancer cells (K562, LS174T) was determined using a MTT assay giving IC(50) values in the low nanomolar. Further cytotoxicity screening of compound 2 conducted by the NCI against a panel of 60 different human cancer cell lines indicated that it was particularly active against several solid tumor cells lines derived from the lung, colon, CNS, skin, and breast.
Bioorganic & Medicinal Chemistry Letters