The discovery and development of potential anticancer drugs from marine sources

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2014-08
Authors
Chock, Christopher H.W
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[Honolulu] : [University of Hawaii at Manoa], [August 2014]
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Abstract
The signal transducer and activator of transcription 3 (STAT3) protein is widely considered to be a valid target for anticancer drug discovery. In the search for STAT3 inhibitors from marine sources, the marine sponge Hyrtios sp. collected from Haleiwa Trench, Oahu and the sea cucumber Holothuria sp. collected from Black Point Beach, Oahu were investigated. Bioassay-guided fractionation of the crude extract from the marine sponge yielded two compounds, 15α-methoxypuupehenol and puupehenone, and evidence for a third compound, 15-hydroxypuupehenol, from the active fractions of the isolation. Derivatives of 15α-methoxypuupehenol were also developed with the goal of preventing the compound from interconverting to puupehenone, but with as little structural modification to the compound as possible, and the bioactivity of 15α-methoxypuupehenol and these derivatives were evaluated. Preliminary work was also completed towards the development of an LC-MS analytical method that could be used to identify the structural modifications that might take place on 15α-methoxypuupehenol when the compound is administered to cancer cells in vitro. From the sea cucumber Holothuria sp., the triterpene glycoside holothurinoside C was isolated as the major compound from one of the active fractions in the bioassay-guided fractionation of the crude extract of the organism. The NMR data presented for the compound in this manuscript are believed to be a correction to the values presented in the literature.
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M.S. University of Hawaii at Manoa 2014.
Includes bibliographical references.
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STAT3
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Theses for the degree of Master of Science (University of Hawaii at Manoa). Chemistry.
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