Synthesis of a water-soluble vitamin D derivative

Authors' Affiliations

Abbas Shilabin, Department of Chemistry, College of Arts and Sciences, East Tennessee State University, Johnson City, TN. Andy Clark, Department of Nutrition, College of Clinical and Rehabilitative Health Sciences, East Tennessee State University, Johnson City, TN. Michael Cartwright, Department of Pathology, Bill Gatton College of Pharmacy, East Tennessee State University, Johnson City, TN.

Location

D.P. Culp Center Ballroom

Start Date

4-5-2024 9:00 AM

End Date

4-5-2024 11:30 AM

Poster Number

61

Name of Project's Faculty Sponsor

Mary Andreae

Faculty Sponsor's Department

Rehabilitative Sciences

Classification of First Author

Undergraduate Student

Competition Type

Competitive

Type

Poster Presentation

Presentation Category

Health

Abstract or Artist's Statement

Vitamin D deficiency is a global health problem that affects approximately 50% of the world’s population. This is problematic because individuals with a vitamin D deficiency have an increased risk for developing and dying from cancer. Since vitamin D is a fat-soluble vitamin, a person’s ability to absorb vitamin D is largely based on their ability to absorb dietary fat. Therefore, for people with gastrointestinal (GI) diseases, such as Celiac or Chron’s disease, their ability to absorb vitamin D will be impaired. Because of this, a water-soluble vitamin D derivative was synthesized by linking vitamin D to polyethylene glycol (PEG). Vitamin D was reacted with pyridine and cooled until 0 ℃. 4-Dimethylaminopyridine (DMAP) and succinic anhydride were then added mixed continuously overnight. The following day the reaction beaker was washed with acetone and then left under a bench hood for five days to allow the acetone to fully evaporate. Next an extraction was done with dichloromethane (DCM) and hydrochloric acid (HCl), and then the product was reacted with DCM, ethylene dichloride (EDC), DMAP, and PEG for 4 days and then quenched with deionized water and filtered. The reaction was monitored with TLC. The result of this synthesis was approximately 34 grams of crude product. In addition to helping people with GI diseases increase their vitamin D absorption, this research has potential in cancer prevention. Previous studies from this lab have shown that in a CACO-2 cell model the vitamin D-PEG derivative absorption increased by 1083% when compared to 1,25-dihydroxyvitamin D. This research can also be applied to studies involving chemotherapy drugs, as research has shown that vitamin D combined with chemo drugs have an increased effectiveness, most likely due to vitamin D’s inhibitory action on p-glycoprotein (a protein that functions as a barrier by keeping toxins and xenobiotics out of cells), as well as its involvement in the regulation of the cell cycle. Future research goals for the vitamin D-PEG product include a dissolution study (for supplemental delivery) and testing in an animal model. This research shows promise not only in treating vitamin D deficiencies but in terms of an additional cancer treatment option for patients.

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Apr 5th, 9:00 AM Apr 5th, 11:30 AM

Synthesis of a water-soluble vitamin D derivative

D.P. Culp Center Ballroom

Vitamin D deficiency is a global health problem that affects approximately 50% of the world’s population. This is problematic because individuals with a vitamin D deficiency have an increased risk for developing and dying from cancer. Since vitamin D is a fat-soluble vitamin, a person’s ability to absorb vitamin D is largely based on their ability to absorb dietary fat. Therefore, for people with gastrointestinal (GI) diseases, such as Celiac or Chron’s disease, their ability to absorb vitamin D will be impaired. Because of this, a water-soluble vitamin D derivative was synthesized by linking vitamin D to polyethylene glycol (PEG). Vitamin D was reacted with pyridine and cooled until 0 ℃. 4-Dimethylaminopyridine (DMAP) and succinic anhydride were then added mixed continuously overnight. The following day the reaction beaker was washed with acetone and then left under a bench hood for five days to allow the acetone to fully evaporate. Next an extraction was done with dichloromethane (DCM) and hydrochloric acid (HCl), and then the product was reacted with DCM, ethylene dichloride (EDC), DMAP, and PEG for 4 days and then quenched with deionized water and filtered. The reaction was monitored with TLC. The result of this synthesis was approximately 34 grams of crude product. In addition to helping people with GI diseases increase their vitamin D absorption, this research has potential in cancer prevention. Previous studies from this lab have shown that in a CACO-2 cell model the vitamin D-PEG derivative absorption increased by 1083% when compared to 1,25-dihydroxyvitamin D. This research can also be applied to studies involving chemotherapy drugs, as research has shown that vitamin D combined with chemo drugs have an increased effectiveness, most likely due to vitamin D’s inhibitory action on p-glycoprotein (a protein that functions as a barrier by keeping toxins and xenobiotics out of cells), as well as its involvement in the regulation of the cell cycle. Future research goals for the vitamin D-PEG product include a dissolution study (for supplemental delivery) and testing in an animal model. This research shows promise not only in treating vitamin D deficiencies but in terms of an additional cancer treatment option for patients.