Isolation, Structure Elucidation, and Total Synthesis of Biologically Active Natural Products from Plants

dc.contributor.authorPresley, Christopher Charlesen
dc.contributor.committeechairKingston, David G. I.en
dc.contributor.committeememberSantos, Webster L.en
dc.contributor.committeememberCarlier, Paul R.en
dc.contributor.committeememberJosan, Jatinderen
dc.contributor.departmentChemistryen
dc.date.accessioned2017-11-07T09:00:18Zen
dc.date.available2017-11-07T09:00:18Zen
dc.date.issued2017-11-06en
dc.description.abstractAs a part of the continuing search for bioactive compounds with the Madagascar International Cooperative Biodiversity Group (ICBG), and in collaboration with the Natural Products Discovery Institute of the Institute for Hepatitis and Virus Research (IHVR), thirteen plant extracts were investigated for antiplasmodial activity, thirteen plant extracts were investigated for antiproliferative activity, and one extract was investigated for inhibitors of the shikimate pathway in Plasmodium falciparum. Bioassay-guided fractionation of the extracts led to the identification of nineteen compounds with both antiplasmodial and antiproliferative activity, and thirteen compounds with only antiproliferative activity. Thirteen of these compounds (2.1 – 2.9, 3.3, 3.4, 4.5, and 5.1) were previously unknown. In addition total synthesis was used to confirm the structure of one new compound (4.5) and two other new natural-product like compounds (4.6 and 4.7) were also synthesized and investigated for antiplasmodial activity.en
dc.description.abstractgeneralPlants have a long history of producing compounds (Natural Products) that have been used as medicines. This dissertation focuses on the isolation of potential anticancer and antimalarial natural products from plants and their structure determination. The isolation of compounds was aided by the use of cell-based bioassays to determine the inhibition of cell growth. Growth inhibition of human ovarian cancer cells (the A2780 cell line) was used to test for potential anticancer activity, and growth inhibition of the malaria-causing parasite Plasmodium falciparum was used to test for potential antimalarial activity. Twenty-seven plant extracts from two different plant libraries were found to have biological activity in one of these bioassays, and bioassay-guided isolation performed on nine of these extracts led to the isolation of thirteen new compounds and fourteen known compounds. The isolation, structure determination, and biological evaluation of all isolated compounds are discussed in this work.en
dc.description.degreePh. D.en
dc.format.mediumETDen
dc.identifier.othervt_gsexam:12994en
dc.identifier.urihttp://hdl.handle.net/10919/79978en
dc.publisherVirginia Techen
dc.rightsIn Copyrighten
dc.rights.urihttp://rightsstatements.org/vocab/InC/1.0/en
dc.subjectNatural Productsen
dc.subjectAntiproliferativeen
dc.subjectAntiplasmodialen
dc.subjectChromaneen
dc.subjectChromeneen
dc.subjectCrinumen
dc.subjectCripowellinen
dc.subjectQuinoloneen
dc.subjectDiterpeneen
dc.subjectTriterpeneen
dc.titleIsolation, Structure Elucidation, and Total Synthesis of Biologically Active Natural Products from Plantsen
dc.typeDissertationen
thesis.degree.disciplineChemistryen
thesis.degree.grantorVirginia Polytechnic Institute and State Universityen
thesis.degree.leveldoctoralen
thesis.degree.namePh. D.en

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