Synthesis of 4-Thiazolidinone Small Molecules as Potential Inhibitors of the Arp2/3 Complex

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