Natural and synthetic bis-indole alkaloids as cytotoxic agents

dc.contributor.authorGerhart, Bruce B.en
dc.contributor.departmentChemistryen
dc.date.accessioned2017-03-10T18:28:53Zen
dc.date.available2017-03-10T18:28:53Zen
dc.date.issued1976en
dc.description.abstractThe National Cancer Institute, in conjunction with the U.S. Department of Agriculture, procured the African tree species Tabernaemontana johnstonii and found that the plant possessed anti-tumor activity in two bioassay tests. Consequently, extraction and systematic fractionation of the plant in conjunction with bioassay monitoring revealed that most of this activity was concentrated in the alkaloidal portion. Purification of active compounds was attempted by open column liquid chromatography with both alumina and silica gel supports and by thin layer and high pressure liquid chromatography on silica gel. A compound was eventually isolated and purified and it proved to be a new bis-indole alkaloid. It was given the name tabernamine and showed an activity of 1.9 μg/ml (ED₅₀) in the PS in vitro system and a T/C % of 125 at a dose of 25 mg/kg in the PS in vivo system. In conjunction with these results and the knowledge of the structure and activity levels of similar alkaloids a new bis-indole alkaloid called peribogamine was synthesized. It was conjectured that this compound would elicit a greater cytotoxic activity since it combined the apparently beneficial qualities of the others. Vobasivindoline was also synthesized since it contained the specified O-N-O triangular dimensions, a pharmacophore feature prevalent in many anti-leukemic drugs. Finally, a synthesis of 19-acetonyl voacamine was attempted as a result of the high activity of the previously isolated isomer 19-acetonyl conodurine.en
dc.description.degreeMaster of Scienceen
dc.format.extentvi, 97 leavesen
dc.format.mimetypeapplication/pdfen
dc.identifier.urihttp://hdl.handle.net/10919/76138en
dc.language.isoenen
dc.publisherVirginia Polytechnic Institute and State Universityen
dc.relation.isformatofOCLC# 33879643en
dc.rightsIn Copyrighten
dc.rights.urihttp://rightsstatements.org/vocab/InC/1.0/en
dc.subject.lccLD5655.V855 1976.G45en
dc.titleNatural and synthetic bis-indole alkaloids as cytotoxic agentsen
dc.typeThesisen
dc.type.dcmitypeTexten
thesis.degree.disciplineChemistryen
thesis.degree.grantorVirginia Polytechnic Institute and State Universityen
thesis.degree.levelmastersen
thesis.degree.nameMaster of Scienceen
Files
Original bundle
Now showing 1 - 1 of 1
Loading...
Thumbnail Image
Name:
LD5655.V855_1976.G45.pdf
Size:
3.79 MB
Format:
Adobe Portable Document Format
Collections