Synthesis and biological evaluation of symmetrically and unsymmetrically substituted alkylpolyamines as potential anti-neoplastic and anti-parasitic agents

• Main Author: Ward, Tracey D
• Format: Dissertation
• Language: English
• Published: Ann Arbor ProQuest Dissertations & Theses 2003
• Subjects: Organic chemistry; Pharmacology; pharmacy sciences
• ISBN: 9780496639823; 049663982X

The polyamines putrescine, spermidine and serine are naturally occurring polycations that are absolutely required for normal cell function, especially in rapidly dividing cells, including parasitic organisms. There have been numerous attempts to develop synthetic agents that interrupt polyamine metabolism in mammalian cells, with the underlying theme that disruption of polyamine metabolism could result in targeted cell death. We have extended our work to the development of anti-parasitic agents and anti-neoplastic agents, and have synthesized a series of terminally alkylated polyamine analogues that have specific anti-parasitic and anti-neoplastic activity both in vitro and in vivo. Further, we have used the results of biological studies to refine a set of structure/function correlations. Our analogues have shown structure dependent activity against a number of targets.