Inhibiting Acid Ceramidase with Phenolphthalein Compounds as a Potential Cancer Treatment

Cancer is a prevalent issue. The most common current treatments for cancer include radiation therapy and chemotherapy. However, recent developments in cancer treatment have included targeted therapy. Targeted therapy drugs are directed at molecules in cancer cells that promote proliferation. This approach to treating cancer is more specific to cancer cells, allowing healthy cells to be unharmed. The focus of our research was to create a targeted therapy drug to inhibit acid ceramidase, an enzyme that functions in the sphingomyelin pathway. The sphingomyelin pathway creates lipids for the plasma membrane of cells. Acid ceramidase converts ceramide into sphingosine, while later in the sphingomyelin pathway, sphingosine is converted into sphingosine-1-phosphate. A high concentration of ceramide in the plasma membrane promotes apoptosis, while a high concentration of sphingosine-1-phosphate promotes cell proliferation. Many cancer cells have increased proliferation due to an overactivity of acid ceramidase. This makes acid ceramidase a promising target for targeted therapy. The goal of our study was to synthesize an effective inhibitor of acid ceramidase. We designed eight derivatives of phenolphthalein, each with different groups attached to the ortho position on the phenols. We then tested each derivative in silico , all of which had promising results. We were able to successfully synthesize all proposed derivatives by reacting 2 equivalents of phenol with phthalic anhydride using an acid catalyst in a microwave. Future works will evaluate the bioavailability of the compounds using tissue culture assays