Formins enhance the assembly of actin filaments, which are part of the cytoskeleton and play important roles in cell motility, cell division, and muscle contraction. Small molecule inhibitor of formin homology 2 (SMIFH2) inhibits formin-regulated actin assembly. Formins have been found to be overexpressed in metastatic cancers, motivating interest in formin inhibition for drug development. Additionally, studies on SMIFH2 and its analogs could lead to a deeper understanding of how formins function in biological systems. We have synthesized a variety of SMIFH2 analogs and tested their biochemical activities with the goals of elucidating structure-function relationships of the inhibitor and finding molecules that selectively inhibit different formin families. Synthetic approaches include application of stoichiometric palladium cross coupling at the aryl bromide site to form the SMIFH2 oxidative addition complex and enable subsequent diversifying cross coupling reactions without the need for catalyst regeneration. Additionally, we have employed Knoevenagel condensations of a thiobarbituric acid core with a variety of aldehydes to generate another diverse set of SMIFH2 analogs for biochemical evaluation.

Synthetic and biochemical studies of the formin inhibitor SMIFH2

Macromolecular Chemistry: The Second Century

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ACS Spring 2020 National Meeting & Expo

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.