Author ORCID Identifier

https://orcid.org/0000-0002-3410-2799

Year of Publication

2021

Degree Name

Master of Science (MS)

Document Type

Master's Thesis

College

Arts and Sciences

Department/School/Program

Chemistry

First Advisor

Dr. Samuel G. Awuah

Abstract

Indoleamine 2 3-dioxygenase (IDO) has recently been highlighted as a promising target for small molecule based immunotherapy. IDO is often coopted by various cancer cells to promote an immune-suppressive environment around tumors. DNA damage repair (DDR) enzymes have recently been targeted for inhibition to promote genetic instability and bolster immune recognition. DDR enzymes such as PARP and POLγ are common inhibition targets due to their direct effects on cellular function. In the process of designing conjugate inhibitors of IDO and DDR enzymes, novel synthetic methodology was developed for the mild deprotection of N-Tert-butyloxycarbonyl (N-BOC) group from various amines. Conjugate inhibitors of IDO and PARP were synthesized using the parent molecules 1-MLT and Olaparib. The conjugate molecules showed more potent cytotoxicity in various cancer cell lines than their precursor molecules. The novel conjugate inhibitors could be used as probes to explore interplay between the PARP and IDO signaling pathways and elucidate any synergy or dependency between the two enzymes.

Digital Object Identifier (DOI)

https://doi.org/10.13023/etd.2021.174

Funding Information

University of Kentucky, Start up funding. 2016

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