Date of Award
Spring 4-21-2026
Document Type
Thesis
Degree Name
Master of Science (MS)
Department
Chemistry
First Advisor
Chae Yi
Second Advisor
James Gardinier
Third Advisor
William Donaldson
Abstract
The Proviral integration site for Moloney Murine Leukemia virus (PIM) kinases belongs to the family of serine/threonine kinases consisting of three isoforms; PIM1, PIM2, PIM3. PIM kinase is involved in multiple cellular processes through the phosphorylation of several proteins within the JAK/STAT pathway, leading to cell proliferation, apoptosis inhibition, cell migration, transcription, and energy metabolism. However, disruption or overexpression of PIM within the cycle can have negative, tumorigenesis effects with increased fatality rates. Currently, there are no FDA approved PIM kinase inhibitors available for specific cancer target therapies, despite the growing need and high demand research interests. It is widely known rhodanine, its derivatives, and additional N-Heterocyclic compounds are chemically significant in the design and development of new drug therapies since they mimic ATP. Utilizing rhodanine and a variety of heteroaryl aldehydes via the Knoevenagel condensation, a series of thioxothiazolidine-4-one compounds were synthesized and evaluated against PIM1 for inhibition potency. Compounds 15-27 showed minimal presence of enzyme activity (0-7%) at a single 25 µM concentration, indicating high potent activity against PIM1. The most potent compounds were (Z)-5-((6-Metthoxypyridin-2-yl) methylene)-2-thioxothiazolidin-4-one (23) and (Z)-5-((6-Bromopyridin-2-yl) methylene)-2-thioxothiazolidin-4-one (18) respectively (IC50= 2.6 ± 0.1 and 10.8 ± 0.64 nM).