Presentation Title

Limiting LOX Expression Through the Development of Pyridine Based Small Molecule Inhibitors

Faculty Mentor

Danielle Solano

Start Date

23-11-2019 10:00 AM

End Date

23-11-2019 10:45 AM

Location

187

Session

poster 3

Type of Presentation

Poster

Subject Area

health_nutrition_clinical_science

Abstract

Lysyl oxidase (LOX) is an enzyme that forms the cross linkages between connective tissues such as collagen and elastin. Research into LOX has found that an upregulation occurs in enzymatic activity when in the presence of cancer cells leading to a metastasis of the cells in the affected area. There have been several compounds that have been found to have the ability of inhibiting the enzyme, one of which being β-aminopropionitrile (BAPN). However, this compound has been found to be cytotoxic when directly administered to the body’s cells. The goal of this project is to explore the mechanism of action taken by the enzyme through the creation of various small molecule inhibitors containing the β-aminopropionitrile group attached that are capable of limiting LOX expression without the cytotoxic effects.

The targeted inhibitors for synthesis include various compounds with heterocyclic rings that are hypothesized to have the capability of limiting LOX expression while being soluble under physiological conditions. Due to prior testing of inhibitors, pyridine-containing BAPN derivatives were prepared from the addition of 3,3-iminopropionitrile to 3-pyridinecarboxaldehyde via reductive amination with pic borane. Along with an additional target prepared using the same methodology with BAPN and 4-quinolinecarboxaldehyde. These molecules were targeted for creation because of prior inhibitors tested which yielded various problems. One of the problems associated with the inhibitors made previously was solubility, so in order to make more soluble compounds, pyridine-based compounds were targeted for derivation.

These products are being purified and yields will be determined. Future developments to be made in this project include the development of other heterocyclic compounds with an increased solubility in physiological conditions and screening of the inhibitors to determine effectiveness in limiting LOX expression.

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Nov 23rd, 10:00 AM Nov 23rd, 10:45 AM

Limiting LOX Expression Through the Development of Pyridine Based Small Molecule Inhibitors

187

Lysyl oxidase (LOX) is an enzyme that forms the cross linkages between connective tissues such as collagen and elastin. Research into LOX has found that an upregulation occurs in enzymatic activity when in the presence of cancer cells leading to a metastasis of the cells in the affected area. There have been several compounds that have been found to have the ability of inhibiting the enzyme, one of which being β-aminopropionitrile (BAPN). However, this compound has been found to be cytotoxic when directly administered to the body’s cells. The goal of this project is to explore the mechanism of action taken by the enzyme through the creation of various small molecule inhibitors containing the β-aminopropionitrile group attached that are capable of limiting LOX expression without the cytotoxic effects.

The targeted inhibitors for synthesis include various compounds with heterocyclic rings that are hypothesized to have the capability of limiting LOX expression while being soluble under physiological conditions. Due to prior testing of inhibitors, pyridine-containing BAPN derivatives were prepared from the addition of 3,3-iminopropionitrile to 3-pyridinecarboxaldehyde via reductive amination with pic borane. Along with an additional target prepared using the same methodology with BAPN and 4-quinolinecarboxaldehyde. These molecules were targeted for creation because of prior inhibitors tested which yielded various problems. One of the problems associated with the inhibitors made previously was solubility, so in order to make more soluble compounds, pyridine-based compounds were targeted for derivation.

These products are being purified and yields will be determined. Future developments to be made in this project include the development of other heterocyclic compounds with an increased solubility in physiological conditions and screening of the inhibitors to determine effectiveness in limiting LOX expression.