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Issue 10, 2005
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Bioreduction activated prodrugs of camptothecin: molecular design, synthesis, activation mechanism and hypoxia selective cytotoxicity

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Abstract

Several water-soluble derivatives (CPT3, CPT3a–d) of camptothecin (CPT) were synthesized, among which CPT3 bearing an N,N′-dimethyl-1-aminoethylcarbamate side-chain was further conjugated with reductively eliminating structural units of indolequinone, 4-nitrobenzyl alcohol and 4-nitrofuryl alcohol to produce novel prodrugs of camptothecin (CPT4–6). All CPT derivatives were of lower cytotoxicity than their parent compound of CPT. In contrast, CPT4 and CPT6 showed higher hypoxia selectivity of cytotoxicity towards tumor cells than CPT. A mechanism by which a representative prodrug CPT4 is activated in the presence of DT-diaphorase to release CPT was also discussed. The bioreduction activated CPT prodrugs including CPT4 and CPT6 are identified to be promising for application to the hypoxia targeting tumor chemotherapy.

Graphical abstract: Bioreduction activated prodrugs of camptothecin: molecular design, synthesis, activation mechanism and hypoxia selective cytotoxicity

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Publication details

The article was received on 24 Feb 2005, accepted on 04 Apr 2005 and first published on 14 Apr 2005


Article type: Paper
DOI: 10.1039/B502813B
Org. Biomol. Chem., 2005,3, 1905-1910

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    Bioreduction activated prodrugs of camptothecin: molecular design, synthesis, activation mechanism and hypoxia selective cytotoxicity

    Z. Zhang, K. Tanabe, H. Hatta and S. Nishimoto, Org. Biomol. Chem., 2005, 3, 1905
    DOI: 10.1039/B502813B

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