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Biological and Chemical Investigation of Cultured Cyanobacteria

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Title: Biological and Chemical Investigation of Cultured Cyanobacteria
Author(s): Kim, Hyunjung
Advisor(s): Orjala, Jimmy
Contributor(s): Swanson, Steven M.; Federle, Michael J.; Murphy, Brian T.; Ho, Yee-Kin
Department / Program: Medicinal Chemistry and Pharmacognosy
Graduate Major: Pharmacognosy
Degree Granting Institution: University of Illinois at Chicago
Degree: PhD, Doctor of Philosophy
Genre: Doctoral
Subject(s): Cyanobacteria Biological evaluation Cytotoxicity 20 S Proteasome Chemical evaluation Structure elucidation
Abstract: Cyanobacteria have been used as a source of natural products for drug development. Previous studies have demonstrated that compounds with cytotoxic activity are widely distributed in cyanobacteria and that the chemical classes of the cytotoxic compounds are diverse. Several compounds derived from cyanobacteria are approved by FDA or under clinical evaluations for cancer treatment, validating that these organisms have great potential as a source for anticancer drugs or drug leads. In this study, over 300 cyanobacteria strains were cultured, harvested, and extracted. A total of 306 cyanobacterial extracts were evaluated for both cytotoxicity using a set of cancer cells (HT-29, MCF-7, NCI-H460, and SF268 as well as a cancer cell panel consisting of 12 different cancer cells) and inhibition of 20S proteasome, an established target for cancer treatment. Of the 306 screened extracts, nine displayed cytotoxicity and seven showed inhibition of 20S proteasome. Five of these bioactive cyanobacterial strains, Fischerella sp. (SAG 46.79), Westiellopsis sp. (SAG 20.93), Fischerella muscicola (UTEX LB1829), Nostoc sp. (UIC 10047), and Oscillatoria sp. (UIC 10109), were selected for chemical investigation. Activity-guided fractionation led to the isolation of 22 compounds. Structures of these isolated compounds were elucidated using a variety of spectroscopic analyses and 9 of 22 were found to be novel compounds. Most of these compounds showed moderate to strong cytotoxicity and/or 20S proteasome inhibition. It has been shown that cyanobacteria have a great potential as a source for discovery of anticancer lead compounds, and the results of this study also support this. We believe that continued efforts on the chemical and biological evaluation of these organisms will provide a great opportunity for the discovery of new anticancer lead compounds.
Issue Date: 2012-12-13
Genre: thesis
URI: http://hdl.handle.net/10027/9488
Rights Information: Copyright 2012 Hyunjung Kim
Date Available in INDIGO: 2012-12-13
Date Deposited: 2012-08
 

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