| Abstract | Pyridinophane molecules have recently been shown to have both antioxidant and pharmacological properties suitable for therapeutic applications targeting neurodegenerative diseases, including Alzheimer's. One pyridinophane in particular (P1) demonstrated remarkable antioxidant ability as both a radical scavenger and metal chelator. While the reactivity of previously synthesized parent was satisfactory, its permeability across the blood-brain barrier was poor. Thus, the Green Group synthesized derivatives of this parent molecule, substituting moieties onto various attachment points on the molecule. These substitutions are designed to enhance the permeability of the parent molecule in the hopes of producing a molecule that is suitable for pharmacological testing in animal models. To establish a principle between substitution and the change in pharmacological properties, we have substituted an indole, a hydrophobic moiety and established antioxidant in our lab, in varying locations on the parent (L1, L2). The results presented here will detail evaluation of the substitution of an indole in varying location and its impact on the molecules pharmacological permeability through a series of measurements, including intestinal absorptivity, metabolic stability in a liver microsome, and blood-brain barrier permeability. |
