Week 1 + 2: Intro And Computational Work
Hello, my name is Vivian, and welcome to my blog! Because this page ran into some technical difficulties the first week, here is a brief introduction to my senior project!
(What’s supposed to be) Week 1:
Dexamethasone is an anti-inflammatory corticosteroid that is commonly used to treat all sorts of inflammatory diseases like arthritis, eczema, and even some forms of cancer. I found dexamethasone very relevant personally as I struggle a lot with eczema, and I am a primary source of using too much corticosteroids. Anyways, corticosteroids are basically man-made hormones and can affect gene expression. In this case, dexamethasone enters the cell and binds to the glucocorticoid receptor; this binding event inhibits the NF-κB signaling pathway, known for enhancing inflammation. As a result, by downregulating the pathway, there is less inflammation! The focus and goal of this project is to synthesize different analogs of dexamethasone, which means producing more dexamethasones but just with slightly different changes, like altering various chemical functional groups. This helps see exactly which properties of the drug are contributing to its effectiveness, and these findings can possibly be applied to corticosteroids in general.
To start off with the project, I performed some computational modeling to give myself an idea of how these analogs might perform. I first came up with a bunch of analogs by altering the stereochemistry (arrangement of the atoms) at C-11, and adding various functional groups (acetate, furoate, and dipropionate groups) in the same position. I docked these analogs and received their various binding affinities to the glucocorticoid receptor. Theoretically, greater binding affinity might correlate to better drug effectiveness, though there are other factors to consider, like its bioavailability (drug absorption by the body). Here are the structures of the analogs I came up with (drawn with Marvinsketch):