What Are Isoxazolines?
Isoxazolines are compounds with an isoxazole ring, the pentagonal ring structure with Nitrogen and Oxygen, shown in the figure below on the right side. The figure details the cyclization process where the oxime, on the left, is converted into the isoxazoline by closing the isoxazole ring.
Isoxazolines have a wide variety of applications, from combating both types of diabetes to possibly acting as a pesticide. The research finds a cost-effective pathway to synthesize the isoxazoline with relatively high yields. This would lower production costs of medicine or any other applications of it which makes it more affordable for the consumers. The isoxazoline produced in the research is similar in structure and a precursor, or starting material, to many other forms of isoxazolines and may have further reactions to transform into other compounds that have useful properties.
The compound above is named ISO-1, and it inhibits Macrophage Migratory Inhibition Factor (MIF) which plays a role in both types of diabetes (Mosher & Norman). ISO-1 is very similar in structure to the isoxazoline produced through this research and would most likely mimic ISO-1's effects. MIF is a pro-inflammatory cytokine which acts as an alarm bell to the immune system (Zamora & Sosa). Type I Diabetes is caused by the destruction of Beta cells in the pancreas, mainly by the immune system, and MIF is directly involved in Type I Diabetes as it promotes the apoptosis of Beta cells in the pancreas by signaling the immune system to destroy the Beta cells in the pancreas (Zamora & Sosa). By inhibiting MIF through ISO-1, the onset of Type I Diabetes would be slowed. There is a correlation between MIF and Type II Diabetes, but the exact nature of MIF is not known with respect to Type II Diabetes.
This has practical applications in counteracting Type II Diabetes by opposing an enzyme called Glycogen Phosphorylase. It binds to an allosteric site on the enzyme, changing the function of the enzyme by changing its structure (Goyard et al). Glycogen Phosphorylase works by breaking down glycogen into glucose, raising blood sugar levels (Goyard et al). Type II Diabetes is characterized by the target cells not absorbing glucose from the blood stream, leading to high blood sugar levels (Ross et al). By inhibiting an enzyme that releases glucose into the blood stream, there will be less sugar in the blood stream, and it will mitigate harmful symptoms.
Protein Tyrosine Phosphatases
Isoxazoline is similar in structure to inhibitors of protein tyrosine phosphatases (PTPase). “A number of these PTPase that act as negative regulators of the insulin signaling cascade have been identified as novel targets for the therapeutic enhancement of insulin action in insulin-resistant disease states like Type II Diabetes” (Maurya, Gupta, & Ahmad).