Document Type

Thesis

Publication Date

Fall 12-3-2010

Advisor

Roman Manetsch

Advisor Email

manetsch@cas.usf.edu

Abstract

β-Secretase is the enzyme responsible for the Amyloid-β plaques found in Alzheimer’s disease. Inhibition of this enzyme should prove to be very useful in combating Alzheimer’s disease by preventing this build-up. After a computational screening of the NCID-2 library a molecule was found to possess a 2- propanol structure with aromatic groups on either side. This moiety was replicated by a combinatorial library of 150 compounds. These compounds were screened initially against β-secretase at 100, 50, and then 25 μM to narrow down to 17 structures showing 50% inhibition at 25 μM. The IC50 for each of the 17 molecules was found experimentally resulting in one lead compound 15, 4.93 μM ± 0.86 μM. This compound was modified by making slight changes to the 2-propanol moiety resulting in mostly loss of activity.

Comments

Chemistry

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