Title of Abstract

Modifying Acid Ceramidase Inhibitors to Encourage Cancer Cell Apoptosis

Faculty Mentor

One WU mentor: T. Christian Grattan, Ph.D.; grattanc@winthrop.edu

College

College of Arts and Sciences

Department

Chemistry, Physics & Geology

Faculty Mentor

T. Christian Grattan, Ph.D.

Abstract

In 2020 alone 1.9 million new cases of cancer were diagnosed. This challenging disease has a multitude of treatments that all hope to cure the cancer completely without recurrence. This research focused on the sphingolipid metabolic pathway with a special interest in ceramidase. Ceramidase, if inhibited, encourages cell apoptosis. The final product of this pathway, sphingosine-1-phosphate, encourages cell growth and proliferation. The goal of this research was to inhibit the activity of ceramidase in hopes of increasing the amount of ceramide in the cell which increases apoptosis in cancer cells. There are multiple types of ceramidase that are present in different cells in different parts of the body. Our research focused on the most common and most researched, acid ceramidase. In order to prevent acid ceramidase from binding with ceramide a variety of known inhibitors were evaluated using in silico docking studies in Chimera and AutoDock Vina. The inhibitors that were determined successful were also compounds known as thymidylate synthase inhibiting compounds. The goal of the research was to identify the compounds that would have the most success in silico and can be later be synthesized and tested in vitro. Our results showed that a compound with two iodine ions, and two isobutyl chains performed the best in silico. Future research for this topic includes accomplishing the synthesis of these pure derivatives and completing in vitro analysis with the target enzyme.

Additional Fields About Your Abstract

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Grant Support

Support was provided by an NIH-INBRE grant from the National Center for Research Resources and the National Institute for General Medical Sciences as well as the Winthrop University

Start Date

1-1-2021 12:00 AM

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Jan 1st, 12:00 AM

Modifying Acid Ceramidase Inhibitors to Encourage Cancer Cell Apoptosis

In 2020 alone 1.9 million new cases of cancer were diagnosed. This challenging disease has a multitude of treatments that all hope to cure the cancer completely without recurrence. This research focused on the sphingolipid metabolic pathway with a special interest in ceramidase. Ceramidase, if inhibited, encourages cell apoptosis. The final product of this pathway, sphingosine-1-phosphate, encourages cell growth and proliferation. The goal of this research was to inhibit the activity of ceramidase in hopes of increasing the amount of ceramide in the cell which increases apoptosis in cancer cells. There are multiple types of ceramidase that are present in different cells in different parts of the body. Our research focused on the most common and most researched, acid ceramidase. In order to prevent acid ceramidase from binding with ceramide a variety of known inhibitors were evaluated using in silico docking studies in Chimera and AutoDock Vina. The inhibitors that were determined successful were also compounds known as thymidylate synthase inhibiting compounds. The goal of the research was to identify the compounds that would have the most success in silico and can be later be synthesized and tested in vitro. Our results showed that a compound with two iodine ions, and two isobutyl chains performed the best in silico. Future research for this topic includes accomplishing the synthesis of these pure derivatives and completing in vitro analysis with the target enzyme.