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    • University of Missouri-Columbia
    • Graduate School - MU Theses and Dissertations (MU)
    • Theses and Dissertations (MU)
    • Dissertations (MU)
    • 2008 Dissertations (MU)
    • 2008 MU dissertations - Freely available online
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    Chemical mechanisms underlying the medicinal activity of metabolically-activated N-oxide antitumor agents

    Junnotula, Venkatraman, 1976-
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    [PDF] research.pdf (2.582Mb)
    Date
    2008
    Format
    Thesis
    Metadata
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    Abstract
    Tirapazamine (TPZ) belongs to a new class of bio-reductively activated hypoxiaselective anti-cancer agents and is currently undergoing in various clinical trials including Phase I, II and III. Anti-cancer activity of TPZ derives from its ability to cause the DNA strand cleavage in oxygen poor environment found in solid tumors. However, the exact nature of DNA damaging agent produced from activated TPZ is not well understood. In our studies, we carried out systematic mechanistic studies to understand the exact nature of DNA damaging agent(s) produced from enzymatically activated TPZ and structurally similar heterocyclic di-oxides. Our data shows that TPZ and its related di-Noxides release known DNA damaging agent hydroxyl radical. Thus, our data suggests that TPZ and its analogs deliver known radiotherapeutic DNA damaging agent hydroxyl radical under oxygen poor environment found in solid tumors.
    URI
    https://doi.org/10.32469/10355/5543
    https://hdl.handle.net/10355/5543
    Degree
    Ph. D.
    Thesis Department
    Chemistry (MU)
    Rights
    OpenAccess.
    This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivs 3.0 License.
    Collections
    • 2008 MU dissertations - Freely available online
    • Chemistry electronic theses and dissertations (MU)

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