Keira Chatwin

Andrographolide, a labdane diterpenoid extracted from Andrographis paniculata, has been investigated as a therapeutic lead for many diseases. Namely, it has been found to exert its biological activity through inhibition of Nf-kB, a transcription factor at the crossroads of a myriad of cell signaling pathways, including those pertaining to tumor survival. Synthesis of derivatives of the natural product has the potential to create analogs and prodrugs of the compound that could improve tolerability, selectivity, and potency. Here we present the synthesis of C-ring modified andrographolide analogs with altered Michael acceptor properties, as well as a series of acid hydrolyzable acetal and ketal analogs, which we assay for controlled delivery and release. We use a quantitative reverse transcriptase PCR (qRT-PCR) assay as a proxy for Nf-kB regulated gene expression.