Date of Award

5-31-2026

Document Type

Open Access Dissertation

Degree Name

Doctor of Philosophy (PhD)

Department

Chemistry/Biological Chemistry

First Advisor

Marianna Torok

Abstract

The major goal of this work was to develop a therapeutic intervention against preeclampsia (PE). Preeclampsia affects up to 5-7% of all pregnancies and has no causative treatments. It is associated with oxidative stress caused by a prolonged ischemic state and increase in reactive oxygen species (ROS) in the placenta. The cardinal symptoms include high blood pressure, kidney dysfunction, and in severe cases, eclampsia. With no treatment for the underlying causes available, we offer small molecule antioxidants which may scavenge ROS in the placenta arising from the initiating event of PE, the oxidative stress. By reducing placental ROS, these antioxidants may help mitigate preeclampsia symptoms. This dissertation includes the following two major projects aiming for the development and evaluation of small molecule antioxidants as potential therapeutics against preeclampsia.

The first project focused on diaryl hydrazone derivatives as potential antioxidants. Different electron-withdrawing and electron-donating groups were added to the diaryl hydrazone scaffold to see how it would affect the antioxidant’s radical scavenging ability. Cationic diaryl hydrazones were also investigated to see if they could penetrate cellular and mitochondrial membranes at a higher percentage than their non-ionic counterpart. The hydrazone derivatives were analyzed in silico to determine potentially viable antioxidants. Once synthesized, the antioxidants were first evaluated by in vitro biochemical assays for their radical scavenging activity. If they passed this checkpoint, the antioxidants were further analyzed with in vitro cell based assays.

The second project focused on sulfur-based antioxidants to evaluate their potential for use as therapeutic agents. Thiophenols were one of the scaffolds that were analyzed by in vitro biochemical assays and compared to their phenol analogues. Sulfonamides, another group with broad bioactivity, were also analyzed with in vitro biochemical assays to determine their viability as antioxidants.

Comments

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