A novel achiral seco-cyclopropylpyrido [e] indolone (CPyI) analog of CC-1065 and the duocarmycins: synthesis, DNA interactions, in vivo anticancer and anti-parasitic …
S Chavda, B Babu, SK Yanow, A Jardim… - Bioorganic & medicinal …, 2010 - Elsevier
Bioorganic & medicinal chemistry, 2010•Elsevier
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 …
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 …
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.
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