Title page for ETD etd-12012005-181123


Type of Document Dissertation
Author Williams, Russell B.
URN etd-12012005-181123
Title Searching for Anticancer Natural Products From the Rainforest Plants of Suriname and Madagascar
Degree PhD
Department Chemistry
Advisory Committee
Advisor Name Title
Kingston, David G. I. Committee Chair
Carlier, Paul R. Committee Member
Gandour, Richard D. Committee Member
Tanko, James M. Committee Member
Taylor, Larry T. Committee Member
Keywords
  • Cytotoxic
  • Anticancer
  • Natural Products
  • Diterpene
  • Naphthaquinone
  • Casimerella ampla
  • Mendoncia cowanii
  • Vernonia pachyclada
  • Casearia nigrescens
  • Sesquiterpene lactone
Date of Defense 2005-11-29
Availability unrestricted
Abstract
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.

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