Triple negative breast cancer is described as being a breast cancer deficient in estrogen (ER), progesterone (PgR), and HER2 receptors. Unfortunately, this deficiency causes the disease to be nonrespondent to hormonal therapy, or therapies that target the classic receptors. In order to effectively treat this type of cancer, we must target different receptors. Liver X Receptors (LXR) ligands have been proven to show anti-proliferative activity and induces cell death in breast cancer. Based on these findings, our aim is to design LXR ligands as anticancer agents. We synthesized the proposed LXR ligands using both traditional and microwave chemistry. Research has shown that a known inverse agonist of the LXR, T0901317, has great affinity for the Liver X receptor. Utilizing the chemical structures of known LXR agonist such as T0901317, we have made structural modifications to the phytochemical, berberine. Berberine is a known anti-tumorigenic, anti-cancer, and anti-viral agent. We hypothesize that structural modifications of berberine may lead to an even more effective LXR ligand, which will increase anti-proliferation and induction of breast cancer cell death. Based on molecular modeling studies, the addition of a new functional group to the berberine skeleton has shown an increase in the binding affinity of berberine greater than the known LXR ligand. We have utilized molecular modeling to aid in the design of Liver X receptor agonist.

Design and synthesis of liver X receptor ligands

2019 Spring National Meeting

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