Event Information
Synthetic Studies toward Analogues of Manassantin A
- Abstract:
In response to oxygen deprivation, tumor cells express a transcription factor, hypoxia inducible factor 1 (HIF-1). HIF-1 regulates the expression of genes involved in erythropoiesis, angiogenesis and other adaptive responses to hypoxia, which encourage cell survival and proliferation. Overexpression of HIF-1 causes increased vascularization and tumor growth, while HIF-1 inhibition reverses these processes. The natural products, manassantins A and B, are potent HIF-1 inhibitors whose molecular mechanisms are unknown. This research aims to establish structure-activity relationships which will aid in the synthesis of manassantin A analogues with ideal drug-like properties. These analogues will be afforded by modifications of the tetrahydrofuran core and side chain regions of manassantin A. Preparation of the key synthetic intermediates of manassantin A analogues is described. Establishment of their pharmacological profiles will provide insight into the HIF-1 signaling pathway and drive the development of these natural products into probes of cancer biology.
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