Date of Award

Fall 2013

Degree Type


Degree Name

Doctor of Philosophy (PhD)



First Advisor

Mark A. Lipton

Committee Chair

Mark A. Lipton

Committee Member 1

Jean A. Chmielewski

Committee Member 2

Alexander Wei

Committee Member 3

Jonathan Wilker


The work in this thesis details the design, synthesis, and biological evaluation of molecular inhibitors for the inhibition of biologically relevant enzymes. The first three chapters of this thesis concern the polyphenol resveratrol and its inhibition of the quinone reductase 2 (QR2) enzyme. The work on this subject resulted in the complete design, synthesis, biological and structural evaluation of a second generation library of resveratrol analogues. From this work we identified a novel resveratrol analogue that inhibits QR2 in a previously unknown binding orientation. The fourth chapter of this thesis details the de novo design of molecules for the inhibition of the Class II HMGR enzyme. The work on this subject involved the de novo design and in silico screening of a set of phenothiazine molecules for the inhibition of II-HMGR. These molecules were synthesized and assayed against II-HMGR, resulting in the identification of a substituted phenothiazine compound found to inhibit II-HMGR with an IC50 of 130 µM. This work resulted in a successful strategy for the identification of II-HMGR inhibitors.