A Novel Achiral Seco-cyclopropylpyrido[e]indolone (CPyI) Analog of CC-1065 and the Duocarmycins: Synthesis, DNA Interactions, in Vivo Anticancer and Anti-parasitic Evaluation
Document Type
Article
Publication Date
7-15-2010
Publication Source
Bioorganic and Medicinal Chemistry
Volume Number
18
Issue Number
14
First Page
5016
Last Page
5024
Publisher
Pergamon-Elsevier Science LTD
ISSN
0968-0896
Abstract
The synthesis of an achiral seco-hydroxy-aza-CBI-TMI analog (8) of the duocarmycins is reported. Its specificity for the DNA minor groove of AT-rich sequences and covalent bonding to adenine-N3 was ascertained by a thermal cleavage assay. Compound 8 was found to be cytotoxic in the nanomolar range against murine and human cancer cells. It was further demonstrated that compound 8 was active against murine melanoma (B16-F0) grown in C57BL/6 mice. Compound 8 was also shown to inhibit the growth of the protozoan parasites Leishmania donovani, Leishmania mexicana, Trypanosoma brucei, and Plasmodium falciparum in culture.
Recommended Citation
Published in: Bioorganic and Medicinal Chemistry, Volume 18, Issue 14, July 15, 2010, pages 5016-5024. Copyright © 2010 Pergamon-Elsevier Science LTD, Oxford. The final published version is available at: http://dx.doi.org/10.1016/j.bmc.2010.05.078
