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

作者：Chavda Sameer; Babu Balaji; Yanow Stephanie K; Jardim Armando; Spithill Terry W; Kiakos Konstantinos; Kluza Jerome; Hartley John A; Lee Moses^*

来源：Bioorganic & Medicinal Chemistry, 2010, 18(14): 5016-5024.

DOI：10.1016/j.bmc.2010.05.078

• Duocarmycins
• Centanamycin
• Achiral
• Minor groove
• DNA
• Alkylation
• Adenine-N3
• Anticancer
• Anti-parasite
• Antimalaria
• Antitrypanosoma
• Antileishmania

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.

• 出版日期2010-7-15