Discovery and Delivery of Bioactive Natural Products

Simple item page
dc.contributor.authorDu, Yongleen
dc.contributor.committeechairKingston, David G. I.en
dc.contributor.committeememberGandour, Richard D.en
dc.contributor.committeememberCarlier, Paul R.en
dc.contributor.committeememberSantos, Webster L.en
dc.contributor.departmentChemistryen
dc.date.accessioned2018-06-26T08:00:45Zen
dc.date.available2018-06-26T08:00:45Zen
dc.date.issued2018-06-25en
dc.description.abstractAs a part of search for bioactive natural products from the plants in collaboration with the Natural Products Discovery Institute (NPDI), ten plant extracts were investigated for their antiplasmodial activity against Plasmodium falciparum Dd2 strain. Twenty-eight compounds were isolated, and twelve of them were new compounds. The structures of all these compounds were determined by analysis of their mass spectrometric, 1D and 2D NMR, and ECD spectrum. Among these natural products, there were three compounds with good antiplasmodial activity, trichospirolide A with an IC50 value of 1.5 μM, malleastrumolide A with an IC50 value of 2.7 μM, and (+)-lariciresinol with an IC50 value of 3.7 μM. In addition to the studies of drug delivery of bioactive natural product, doxorubicin, a novel thiolated doxorubicin analog were designed and synthesized. Its analogs and PEG stabilizing ligands were then conjugated to gold nanoparticles and the resulting Au-Dox constructs were evaluated by TEM. The release of native drug can be achieved by the action of reducing agents, and that reductive drug release gave the cleanest drug release.en
dc.description.abstractgeneralNatural products from plants have been used as medicines for a very long history, with the best known example of antimalarial drugs. There were two famous antimalarial natural products used as medicines. The first one is an alkaloid, quinine which was isolated from cinchona bark in 1817. Its analog chloroquine was discovered in 1934 and was very effective. But in 1950’s the Plasmodium parasite developed resistance and chloroquine resistant plasmodia were widely spread all over the world. Today, the major antimalarial drug is a sesquiterpenoid, artemisinin which was isolated from artemisia in 1972. Unfortunately, the first report on drug resistance to artemisinin derivative have appeared in 2010. In the future, artemisinin may be useless. So we need to discover new antimalarial natural products. This dissertation focuses on the isolation and structural elucidation of fourteen new natural products with potential antimalarial activities from ten plant extracts.en
dc.description.degreePh. D.en
dc.format.mediumETDen
dc.identifier.othervt_gsexam:15423en
dc.identifier.urihttp://hdl.handle.net/10919/83762en
dc.publisherVirginia Techen
dc.rightsIn Copyrighten
dc.rights.urihttp://rightsstatements.org/vocab/InC/1.0/en
dc.subjectNatural Productsen
dc.subjectAntiplasmodialen
dc.subjectAntiproliferativeen
dc.subjectSesquiterpenoiden
dc.subjectNeolignanen
dc.subjectDiterpenoiden
dc.subjectCoumarinen
dc.subjectButanolideen
dc.titleDiscovery and Delivery of Bioactive Natural Productsen
dc.typeDissertationen
thesis.degree.disciplineChemistryen
thesis.degree.grantorVirginia Polytechnic Institute and State Universityen
thesis.degree.leveldoctoralen
thesis.degree.namePh. D.en

Files

Original bundle
Now showing 1 - 1 of 1
Thumbnail Image
Name:
Du_Y_D_2018.pdf
Size:
14.9 MB
Format:
Adobe Portable Document Format
Download

Collections

Doctoral Dissertations