Synthesis of Novel Thiazole Inhibitors of Intestinal Alkaline Phosphatase

Abstract

Alkaline phosphatases (APs) are a group of homodimeric metalloenzymes that hydrolyze monophosphate esters. The overexpression of Intestinal Alkaline Phosphatase (IAP) is associated with a variety of diseases. By inhibiting IAP these diseases can be more effectively treated or prevented. Thiazoles are aromatic heterocycles containing sulfur and nitrogen, with a wide range of pharmacological properties. This study focused on synthesizing thiazole derivatives and testing if they can inhibit IAP. Enzyme inhibition was tested by measuring the Km and Vmax of the enzyme reaction. Km and Vmax were derived from Lineweaver-Burke plots created from the reaction rates of a series of reactions. Reaction rates were determined by measuring the absorbance of p-nitrophenoxide produced by the enzyme in a spectrophotometer. Overall, we were successfully able to synthesize the thiazole derivatives and found they uncompetitively inhibited IAP.

Department: Biological Sciences

Faculty Mentor: Dr. Tina Bott