Type of Document Dissertation Author Murphy, Brian Thacher URN etd-11152007-122510 Title Isolation and Structure Elucidation of Antiproliferative Natural Products from Madagascar Degree PhD Department Chemistry Advisory Committee
Advisor Name Title Kingston, David G. I. Committee Chair Carlier, Paul R. Committee Member Gibson, Harry W. Committee Member Riffle, Judy S. Committee Member Tanko, James M. Committee Member Keywords
- Chemistry; Cancer; Natural Products; Biodiversity
Date of Defense 2007-11-07 Availability unrestricted Abstract
As part of an ongoing search for bioactive natural products from the endemic rainforests and surrounding ocean in Madagascar, a total of four extracts were comprehensively studied and were found to contain novel and/or bioactive compounds. The following dissertation discusses the isolation, structure elucidation, and bioactivity studies of these isolates.
The following compounds from plants of Madagascar’s rainforest are discussed in the order they were studied: flavonoids and long-chain compounds from Schizolaena hystrix, a cyclohexene derivative and butenolides from Artabotrys madagascariensis, and limonoids from Malleastrum sp. From the Malagasy marine ascidian Trididemnum sp. collected in the Indian Ocean, the identification as well as the potential biosynthetic origin of polyketide derived bistramides is reported.
In an attempt to explore other facets of natural products chemistry, the second part of this dissertation discusses the process of designing potential anticancer agents based on the scaffold of a natural product. The biomolecular target of these studies is an enzyme that is overexpressed in tumor cells, namely Cdc25B, whose inhibition catalyzes cell cycle arrest at the G2/M transition of the cell cycle. Several analogs of a potent Cdc25B inhibitor were synthesized and tested in the enzyme-based assay.
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