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    Cross-linking and sequence-specific alkylation of DNA by aziridinylquinones. 3. Effects of alkyl substituents.

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    Authors
    Hargreaves, Robert H J
    O'Hare, C Caroline
    Hartley, John A
    Ross, David
    Butler, John
    Affiliation
    CRC Section of Drug Development and Imaging, Paterson Institute for Cancer Research, Christie Hospital NHS Trust, Manchester M20 9BX, U. K.
    Issue Date
    1999-06-17
    
    Metadata
    Show full item record
    Abstract
    The cytotoxicities and DNA cross-linking abilities of several alkyl-substituted diaziridinylquinones have been investigated. The cytotoxicities were determined in DT-diaphorase-rich (H460 and HT29) and -deficient (H596 and BE) cell lines. It was shown that the cytotoxicities in these cell lines correlated with the relative rates of reduction by the purified human enzyme and with the cross-linking efficiencies. The rates of reduction by DT-diaphorase were more dependent on the structures of the compounds than the reduction potentials, as determined by cyclic voltammetry. A computer model was also used to explain high efficiency of cross-linking and the GNC sequence selectivity of the reduced methyl-substituted diaziridinylquinones.
    Citation
    Cross-linking and sequence-specific alkylation of DNA by aziridinylquinones. 3. Effects of alkyl substituents. 1999, 42 (12):2245-50 J. Med. Chem.
    Journal
    Journal of Medicinal Chemistry
    URI
    http://hdl.handle.net/10541/91340
    DOI
    10.1021/jm991007y
    PubMed ID
    10377230
    Type
    Article
    Language
    en
    ISSN
    0022-2623
    ae974a485f413a2113503eed53cd6c53
    10.1021/jm991007y
    Scopus Count
    Collections
    All Paterson Institute for Cancer Research

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