Date of Award

5-2020

Document Type

Thesis

Degree Name

Master of Science (MS)

College/School

College of Science and Mathematics

Department/Program

Chemistry and Biochemistry

Thesis Sponsor/Dissertation Chair/Project Chair

David Rotella

Committee Member

Nina Goodey

Committee Member

Magnus Bebbington

Abstract

With increasing age, individuals begin to experience cognitive decline, especially memory deficits. Given the lack of effective treatments for memory loss, a new promising approach includes targeting second messenger systems that play a critical role in cognitive processes by inhibiting phosphodiesterases (PDEs), specifically PDE11A since its expression is restricted to the brain. PDE11A is responsible for regulating levels of second messengers, such as cyclic AMP and cyclic GMP, which participate in several biochemical processes relating to long term memory function. Since these signaling cascades are controlled by PDEs that result in turning off the signaling pathway, inhibiting phosphodiesterases will lead to an elevated level of cyclic nucleotides and in turn restore memory function. Based on a PDE11A inhibitor identified during an initial screening, a variety of bisamide and sulfonamide analogs were synthesized to test if they have improved potency and selectivity for PDE11A. Given the limited information regarding the structure activity relationship, this data provided insight on the structure affects the biological activity.

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