Phidianidine A and B have been shown to have a range of biological activities. These molecules consist of three distinct regions: indole, 1,2,4-oxadiazole, and side chain. Analogues of these molecules that introduce a biaryl side chain have been reported to protect nerve cells from oxidative damage. This type of damage implicated in the onset and progression of neurodegenerative diseases such as Alzheimer’s. We have developed a synthetic approach to these phidianidine analogues that allows for the indole region to be varied. These novel compounds have been tested in Caenorhabditis elegans, an established model for observing oxidative stress. Coupling KillerRed, a photosensitive protein that generates reactive oxygen species when illuminated, to GABA neurons in C. elegans creates a clear, nonlethal phenotypic response due to neurodegeneration. The goal of this project is to identify new phidianidine analogues using C. elegans that provide greater protection against oxidative damage.

Synthesis of biological evaluation of phidianidine analogues as neuroprotective agents

255th National Meeting (2018)

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