Submission Title
Synthesis of 4-Thiazolidinone Small Molecules as Potential Inhibitors of the Arp2/3 Complex
Faculty Sponsor(s)
Andrew Baggett
Location
Jereld R. Nicholson Library: Grand Avenue
Subject Area
Chemistry
Description
Life-essential cellular processes such as endocytosis, motility, and division rely on a cell’s ability to precisely regulate construction of actin filaments in response to external factors and signals. Intrinsically involved in this process is the Actin Related Protein 2/3 (Arp2/3) Complex, a seven-subunit ATPase that functions by nucleating a daughter branch of actin from the side of a pre-existing microfilament. Active Arp2/3 complex is necessary for the proliferation of certain metastatic cancers, and inhibition of Arp2/3 complex is emerging as a potentially useful treatment strategy for such cancers. We describe synthesis and in vitro assays of 4-thiazolidinones predicted by computational methods to inhibit of Arp2/3 Complex strongly, and therefore serve as potential lead compounds for drug development. Known Arp2/3 inhibitor CK-869 serves as the starting point for derivative synthesis. We discuss the efforts towards the synthesis of new compounds and the biochemical data collected about their potency.
Recommended Citation
Smith, Haley; Nolen, Brad J.; and Baggett, Andrew W., "Synthesis of 4-Thiazolidinone Small Molecules as Potential Inhibitors of the Arp2/3 Complex" (2019). Linfield University Student Symposium: A Celebration of Scholarship and Creative Achievement. Event. Submission 44.
https://digitalcommons.linfield.edu/symposium/2019/all/44
Synthesis of 4-Thiazolidinone Small Molecules as Potential Inhibitors of the Arp2/3 Complex
Jereld R. Nicholson Library: Grand Avenue
Life-essential cellular processes such as endocytosis, motility, and division rely on a cell’s ability to precisely regulate construction of actin filaments in response to external factors and signals. Intrinsically involved in this process is the Actin Related Protein 2/3 (Arp2/3) Complex, a seven-subunit ATPase that functions by nucleating a daughter branch of actin from the side of a pre-existing microfilament. Active Arp2/3 complex is necessary for the proliferation of certain metastatic cancers, and inhibition of Arp2/3 complex is emerging as a potentially useful treatment strategy for such cancers. We describe synthesis and in vitro assays of 4-thiazolidinones predicted by computational methods to inhibit of Arp2/3 Complex strongly, and therefore serve as potential lead compounds for drug development. Known Arp2/3 inhibitor CK-869 serves as the starting point for derivative synthesis. We discuss the efforts towards the synthesis of new compounds and the biochemical data collected about their potency.
