Searching for Anticancer Natural Products From the Rainforest Plants of Suriname and Madagascar

Through the ICBG (International Cooperative Biodiversity Group) program and a continuing search for anticancer compounds, plant extracts were obtianed from Suriname and Madagascar and screened for cytotoxic activity in the A2780 human ovarian cancer cell line. Fractionation of a leaf and flower extract of Casearia nigrescens led to the isolation of six new clerodane diterpenes. Four were new natural products and the other two were previously unreported hydrolysis products. Their structures were determined using mass spectrometry and 1-D and 2-D NMR. All six compounds were cytotoxic in the A2780 human ovarian cancer cell line. Fractionation of a leaf extract of Vernonia pachyclada led to the isolation of four new sesquiterpene lactones. Their structures were determined using mass spectrometry, 1-D and 2-D NMR, and (in one case) single crystal X-ray diffraction. All four compounds were cytotoxic in the A2780 human ovarian cancer cell line. Fractionation of an extract of Casimirella ampla led to the isolation of three new diterpenes and two known diterpenes. Their structures were determined using mass spectrometry and 1-D and 2-D NMR. All five compounds were cytotoxic in the A2780 human ovarian cancer cell line. Fractionation of root and stem extracts of Mendoncia cowanii led to the isolation of two new naphthaquinones, and two known naphthaquinones. Their structures were determined using mass spectrometry and 1-D and 2-D NMR. All four compounds were cytotoxic in the A2780 human ovarian cancer cell line and three compounds exhibited weak inhibition of Akt kinase. The fractionation of five additional extracts resulted in the isolation of twelve known compounds. Their structures were determined using mass spectrometry, 1-D and 2-D NMR, and comparison to literature data. All twelve compounds were cytotoxic in the A2780 human ovarian cancer cell line.

Name thesis:degree_name

Ph. D.

Level thesis:degree_level

doctoral

Discipline thesis:degree_discipline

Chemistry

Department dc:contributor.department

Chemistry

Grantor dc:publisher

Virginia Tech

Year dc:date.issued

2005

Author dc:creator

• Williams, Russell B.

Chair dc:contributor.committeechair

• Kingston, David G. I.

Committee members dc:contributor.committeemember

• Carlier, Paul R.
• Gandour, Richard D.
• Tanko, James M.
• Taylor, Larry T.

• Cytotoxic
• Anticancer
• Natural Products
• Diterpene
• Naphthaquinone
• Casimerella ampla
• Mendoncia cowanii
• Vernonia pachyclada
• Casearia nigrescens
• Sesquiterpene lactone

Statement dc:rights

• In Copyright

Licence dc:rights.uri

• http://rightsstatements.org/vocab/InC/1.0/

Dc Identifier Other

etd-12012005-181123

OAI identifier oai:identifier

oai:vtechworks.lib.vt.edu:10919/29861