Document Type

Thesis

College

College of Pharmacy and Health Sciences

Department

Pharmaceutical and Administrative Sciences

Degree

MS in Pharmaceutical Sciences

Date Completed

Spring 2024

First Committee Member

Kinney, Shannon

Second Committee Member

Ghoneim, Ola

Abstract

Objectives: To design analogs of natural products with known anticancer and anti-inflammatory activities. Then assess the effects of the compounds on the cell viability of the HCT116 colorectal cancer cell line. Rationale: Analogs of natural products isolated from plants consumed in our diet and with reported anticancer activity, will potentially have activity against colorectal cancer. Methods: Analogs of stilbenes and anethole were synthesized in one step through Wittig reactions. Analogs of caffeic acid were synthesized in one-step reactions using caffeic acid as starting material, N, N′-Dicyclohexylcarbodiimide (DCC) and amines of varying sizes and polarities. The compounds were isolated using automated flash chromatography and the chemical structure was confirmed by nuclear magnetic resonance (NMR). The analogs and parent compounds were tested for their ability to inhibit the cell viability of HCT 116 cells using the MTS assay. Results: A total of six stilbenes and four caffeic acid analogs were successfully synthesized. The synthesis of menthol analogs could not be accomplished and anethole analogs could not be purified. All parent and derivative compounds showed varying concentration dependent levels of anticancer activity, except for caffeic acid. Conclusions: A total of ten derivative compounds were successfully synthesized with moderate yields. Proton and carbon NMR spectra confirmed the structures of the compounds. Most stilbenes exhibited a clear concentration dependent decrease in cell viability, with some appearing to be better than the parent compound. The caffeic acid analogs showed better activity than the parent compound, especially at the highest dose tested.

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