Endometriosis is a chronic inflammatory disease in which endometrial tissue, normally found inside the uterus, is found in other regions of the body. This leads to chronic pain, heavy menstrual cycles, and an increased risk of infertility for affected women. One pathway through which the disease progresses is the abnormal expression of the protein aromatase. Aromatase produces estradiol, the biologically active form of estrogen, from its substrate androstenedione. Aromatase inhibitor drugs have the potential to reduce symptoms of endometriosis. Currently, there are four aromatase inhibitor drugs on the market: letrozole, exemestane, anastrozole, and testolactone. However, these drugs can be problematic because they have numerous unwanted side effects, including skin conditions, loss of bone density, and depression. The goal of this project is to find a new aromatase inhibitor that could treat endometriosis with fewer side effects than the existing drugs. This project focuses on isoflavanones, a class of molecules structurally similar to the natural substrate of aromatase, androstenedione. Recent literature has suggested that isoflavanones may work as aromatase inhibitors with less harmful side effects than current drugs. In this project, a list of possible ligands was compiled based off of the isoflavanone scaffold (Figure 1). Various computational chemistry programs, such as AMBER’s molecular dynamics (MD) and MMPBSA, were then used to assess the binding of each ligand to aromatase. Many of these ligands have shown promise as potential aromatase inhibitor drugs for the treatment of endometriosis.

Computational drug design of aromatase inhibitors as a treatment for endometriosis

ACS Spring 2022

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