Synthetic derivatives of Solenopsin A

UNCG Author/Contributor (non-UNCG co-authors, if there are any, appear on document)
Michael Robert Baker (Creator)
The University of North Carolina at Greensboro (UNCG )
Web Site:
Phillip Bowen

Abstract: Malignant neoplasm is a condition that encompasses many disease states. One unifying theme of these broadly diverse diseases is the requirement for angiogenesis, the formation of new blood vessels, as a prerequisite for tumor growth and metastasis. Because abnormal cell proliferation requires sufficient blood supply, one method for slowing tumor growth may be altering tumor vasculature with angiogenic inhibitors. The Center for Drug Discovery, headed by Dr. Phillip Bowen, in collaboration with Dr. Jack Arbiser at the Emory University School of Medicine, have recently discovered that the natural compound, solenopsin A, is an effective inhibitor of angiogenesis. Solenopsin A's potent antiangiogenic activity was first identified using SVR proliferation assays. To probe the mode of action in which solenopsin A was inhibiting angiogenesis, further studies were conducted in cells. These studies suggest that solenopsin A is suppressing the phosphatidylinositol-3-kinase (PI3K)/Akt pathway by inhibiting a step in the signaling cascade upstream PI3K. The ultimate goal of this work is to develop an antiangiogenic drug based on solenopsin A. Our immediate research objective, however, is to explore structure- activity relationships for benzamide, ether, and amine side chain analogs of solenopsin A. Benzamide analogs of solenopsin A were first synthesized and screened for antiangiogenic activity using the SVR assays conducted at the Emory SOM. The assay results indicate that none of the analogs tested were antiangiogenic. To further explore the structural effects on angiogenic inhibition, ether side chain analogs were synthesized with varying alkyl chain lengths and the benzamide derivatives, previously synthesized, were reduced to amine side chain analogs. To assess the effect of n-alkyl chain length on angiogenic inhibition, one long-chain analog was also generated. These ether, amine, and long-chain analogs are under consideration for testing using the SVR assays.

Additional Information

Language: English
Date: 2012
Malignant neoplasm, Angiogenesis
Fire ants $x Venom $x Therapeutic use
Cancer $x Treatment
Neovascularization inhibitors $x Therapeutic use

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