Synthesis of potential Plasmodium falciparum heat shock protein 70 modulators

WCC 17

Nora Jameson1, Jeffrey Brodsky2, and Peter Wipf1. (1) Department of Chemistry, University of Pittsburgh, Parkman Ave. CSC 906, Pittsburgh, PA 15260, (2) Department of Biological Sciences, University of Pittsburgh, 274A Crawford Hall, 4249 Fifth Avenue, Pittsburgh, PA 15260
Dihydropyrimidines formed by a Biginelli reaction possess interesting pharmacological properties such as acting as Heat Shock Protein 70 modulators. Using multifunctionalized Biginelli scaffolds as the primary template and then forming larger heterocyclic molecules via a copper catalyzed amidation reaction, a library can be synthesized.

These novel heterocyclic molecules were designed based on the chemistry of previously identified agents impacting the viability of P. falciparum, the causative agent of malaria. We are now reporting extensions of these projects toward a 2nd generation chemical library.

After completion of the synthesis, the potencies of the derived agents will be examined both in assays that measure P. falciparum viability and in vitro. The in vitro assay will employ purified Plasmodium falciparum heat shock protein 70 isolated from Escherichia coli. The rationale for this assay is that some existing anti-malarial agents inhibit chaperone function, albeit with low specificity.

 

The Merck Index Women in Chemistry
2:30 PM-4:30 PM, Monday, August 17, 2009 Walter E. Washington Convention Center -- Hall D, Poster

Women Chemists Committee

The 238th ACS National Meeting, Washington, DC, August 16-20, 2009