Synthetic and molecular modeling studies of antiangiogenic compounds based on Solenopsin A lead structure

UNCG Author/Contributor (non-UNCG co-authors, if there are any, appear on document)
Shavon L. Ford (Creator)
Institution
The University of North Carolina at Greensboro (UNCG )
Web Site: http://library.uncg.edu/
Advisor
Phillip Bowen

Abstract: The imported fire ants, Solenopsis invicta, were introduced into the United States by way of Alabama in the mid 1930s. Their devastating impact on the agriculture of the south led to a project to eradicate them, which in turn resulted in the discovery of the antiangiogenic activity of a component of their venom. The discovery of 2-methyl-6-alkyl piperidines has led to the synthesis and study of solenopsin A, a trans-2-methyl-6-n-undecyl piperidine and analogs. Solenopsin A has proven effective in biological testing of zebrafish for antiangiogenic studies, thus qualifying it and its analogs as viable candidates for further studies. Angiogenesis, a term coined by P. Shubik in 1968, is the growth of blood vessels from previously existing vessels. Angiogenesis is a normal physiological process in humans during early childhood development, but seldom in adults. The dominant disease that is affected by angiogenesis is cancer, which progresses through tumor growth. Angiogenesis inhibition, also termed antiangiogenesis, appears to have a very exciting future in cancer therapy. Antiangiogenic molecules have been prepared and studied as potential new therapeutics, and they should be advantageous over the commonly used cancer therapies. Several Williamson ether techniques were investigated to develop analogs of solenopsin A to submit for biological testing as antiangiogenic agents. Computational chemistry techniques were utilized to gain insight into conformation preferences for the ether products. Each molecule was calculated using quantum and molecular mechanics in Spartan. The calculations were performed using equilibrium geometry and the Hartree-Fock model with the 6-31G* basis set. Each structure was subject to a molecular mechanics conformer search followed by quantum mechanical calculations for the lowest energy conformers. The dihedral angles were recorded for each conformer, and again for the minimized conformers.

Additional Information

Publication
Thesis
Language: English
Date: 2009
Keywords
Solenopsis invicta,
Subjects
Cancer $x Treatment $x Research.
Neovascularization inhibitors.
Neovascularization, Pathologic.
Neovascularization, Physiologic.
Solenopsis invicta.
Fire ants $x Research.

Email this document to