In silico binding analysis of sphingosine kinase 1 inhibitors for improved oral bioavailability
Session Title
Physical Sciences
Faculty 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
Sphingosine kinase is a naturally occurring enzyme that exists along the sphingomyelin pathway that is responsible for actively converting sphingosine into sphingosine-1-phosphate (S1P). S1P is linked to the proliferation of cancerous cells and tumors development throughout the body. Sphingosine kinase has been shown to exist at high concentrations in cancerous cells because of this anti-apoptotic outcome. Using UCSF Chimera, Marvin Sketch, Molinspiration, and Autodock Vina, data was collected about the binding energies of the proposed sphingosine kinase 1 inhibitor molecules. The properties of these structures were calculated using Molinspiration, and Marvin Sketch was used to build the structures. The LogP value, and molecular weight were the two properties focused on in this project. The lowest recorded LogP was 1.32, and the highest recorded LogP was 5.58. The latter value violates Lipinski’s Rule of Five making it a less desirable drug candidate. After docking the inhibitor into the enzyme using Chimera and Autodock Vina, the binding energies of the proposed molecules were reported. It was found that the lowest binding energy was -11.3, while the highest was -9.6. Using this information, it was noticed that there may be a correlation between polarity and binding energy. One interesting compound was identified as a potential sphingosine kinase 1 enzyme inhibitor called amygdalin. A synthetic scheme was developed to prepare this compound and ultimately have it evaluated for inhibitory activity.
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Course Assignment
MCNR 300 - Fortner-Wood
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 Department of Chemistry, Physics, and Geology. McNair Scholars Program
Start Date
16-4-2021 3:30 PM
In silico binding analysis of sphingosine kinase 1 inhibitors for improved oral bioavailability
Sphingosine kinase is a naturally occurring enzyme that exists along the sphingomyelin pathway that is responsible for actively converting sphingosine into sphingosine-1-phosphate (S1P). S1P is linked to the proliferation of cancerous cells and tumors development throughout the body. Sphingosine kinase has been shown to exist at high concentrations in cancerous cells because of this anti-apoptotic outcome. Using UCSF Chimera, Marvin Sketch, Molinspiration, and Autodock Vina, data was collected about the binding energies of the proposed sphingosine kinase 1 inhibitor molecules. The properties of these structures were calculated using Molinspiration, and Marvin Sketch was used to build the structures. The LogP value, and molecular weight were the two properties focused on in this project. The lowest recorded LogP was 1.32, and the highest recorded LogP was 5.58. The latter value violates Lipinski’s Rule of Five making it a less desirable drug candidate. After docking the inhibitor into the enzyme using Chimera and Autodock Vina, the binding energies of the proposed molecules were reported. It was found that the lowest binding energy was -11.3, while the highest was -9.6. Using this information, it was noticed that there may be a correlation between polarity and binding energy. One interesting compound was identified as a potential sphingosine kinase 1 enzyme inhibitor called amygdalin. A synthetic scheme was developed to prepare this compound and ultimately have it evaluated for inhibitory activity.
