Vivian L. 2023 | BASIS Independent Silicon Valley
- Project Title: Synthesis of Novel Fluorinated Corticosteroid Analogs of Dexamethasone as Anti-inflammatory Agents
- Basis Independent Advisor: Dr. Ivana Bozidarevic
- Internship Location: Aspiring Scholars Distinguished Research Program
- Onsite Mentor: Edward Njoo
Corticosteroids are a type of anti-inflammatory drug derived from steroids or hormones to bind to a receptor in the nucleus to induce transcription and gene upregulation or downregulation. Dexamethasone is a highly potent and fluorinated corticosteroid that is commonly used to treat diseases including arthritis, asthma, and skin conditions. As a glucocorticoid, a class within corticosteroids, the drug binds to the glucocorticoid receptor (GR), which inhibits the NF-κB signaling pathway that promotes inflammation, thereby producing anti-inflammatory effects. The stability of the drug, target selectivity to GR, and thus overall efficiency may be improved through the synthesis of dexamethasone analogs with selective alcohol functionalization. The first steps, which will all be conducted at the Aspiring Scholars Directed Research Program, include specifically targeting the hydroxyl group at C-11 to attach on different functional groups, including esters or ketones; however, this also involves installing either an acetonide or TBS-protecting group onto the D-ring hydroxyls. To test the effectiveness of the synthesized analogs, inflammation assays will be conducted; the activation of inflammasomes (depending on the levels of the inflammatory response in the treated cells) leads to signaling cascades where the enzyme luciferase is eventually activated to produce bioluminescence, which is then measured. Computational modeling was additionally performed to calculate their relative binding affinities in order to gain insight on currently existing dexamethasone analogs. Conducting this research will provide a better understanding towards synthesizing efficient corticosteroids for better drug treatment covering a wide range of conditions and diseases.