College of Graduate Studies: Theses & Dissertations

Term of Award

Summer 2026

Degree Name

Master of Science in Applied Physical Science (M.S.)

Document Type and Release Option

Thesis (restricted to Georgia Southern)

Copyright Statement / License for Reuse

Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.

Department

Department of Chemistry and Biochemistry

Committee Chair

Shainaz Landge

Committee Member 1

Rebecca Kocerha

Committee Member 2

Rocio Perez

Abstract

Pyridazines are six-membered nitrogen heterocycles with an N-N bond that yields a strong molecular dipole, robust hydrogen-bonding capacity, and favorable physicochemical properties that have established them as privileged scaffolds in both medicinal chemistry and agrochemistry. Conventional routes to pyridazines frequently demand transition-metal catalysts, elevated temperatures, and lengthy multistep sequences that run counter to the principles of green chemistry. This work develops a one-pot, room-temperature synthesis of 3,4,6-trisubstituted (triaryl) pyridazines that utilizes a binary ionic-liquid catalyst system; the basic tetrabutylammonium hydroxide component promotes the initial aldol condensation, while a neutral pyridinium ionic liquid electrostatically activates the carbonyl groups toward cyclization with hydrazine, eliminating the need for external heat or a metal catalyst. A library of para-substituted derivatives was prepared and characterized by ¹H- and ¹³C-NMR spectroscopy and melting-point analysis. Because protein tyrosine phosphatases such as PTP1B and PRL-3 are validated yet under-drugged oncogenic targets implicated in tumor progression and metastasis, the library was screened as phosphatase inhibitors. Enzymatic inhibition assays, Hammett correlation analysis, and half-maximal inhibitory concentration (IC₅₀) determination demonstrated that electron-withdrawing para substituents enhance the inhibition of both PTP1B and PRL-3, with the 4-cyanophenyl derivative emerging as the most potent PTP1B inhibitor (IC₅₀ ≈ 28.5 µM). Cytotoxicity was subsequently evaluated in BT549 triple-negative breast cancer cells using the MTS assay, in which the 4-fluorophenyl derivative produced the greatest reduction in cell viability (64%) along with distinct changes in cell morphology. In A549 lung carcinoma cells, the same 4-fluorophenyl derivative was likewise the most cytotoxic, reducing the mean nuclei count measured by confocal microscopy to approximately 5% of the vehicle control. Collectively, these findings establish a sustainable synthetic platform for functionalized pyridazines and structure-activity relationships that support their continued development as phosphatase-targeted anticancer agents.

Research Data and Supplementary Material

No

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