Natural and synthetic bis-indole alkaloids as cytotoxic agents

• Main Author: Gerhart, Bruce B.
• Other Authors: Chemistry
• Format: Others
• Language: en
• Published: Virginia Polytechnic Institute and State University 2017
• Subjects: LD5655.V855 1976.G45
• Online Access: http://hdl.handle.net/10919/76138

The 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. === Master of Science