Trial Lecture and Thesis Defense - Karoline Nordli

Master of Science Karoline Nordli will hold the Trial Lecture and Thesis Defense for the PhD degree in Science on Friday, October 2, 2026.

Trial Lecture

The Trial Lecture will take place 10:15 - 11:15.

The title of the Trial Lecture is:

« Buchwald-Hartwig Cross Coupling Reaction and Mechanism in the formation of carbon-nitrogen bonds »

Thesis Defense

The Thesis Defense will take place 12:15 - 15:00.

The title of the thesis is:

« CB-103/Medetomidine-Inspired Diaryl Scaffolds: Method Development, Library Construction, and Multitarget Biological Profiling with Exploratory Radiochemistry for Nuclear Imaging Applications »

Abstract

This thesis describes the design, synthesis, and biological evaluation of novel diaryl-based small molecules inspired by the pharmacophores of CB-103 and medetomidine. The work combines medicinal chemistry, radiochemistry, and biological screening to explore the potential of these compounds for both molecular imaging and antifouling applications.

The primary objective was to develop a chemical library targeting the Notch signaling pathway, with the long-term goal of identifying novel radiopharmaceutical candidates for positron emission tomography (PET) imaging of glioblastoma multiforme (GBM). GBM is an aggressive brain cancer with poor prognosis and limited treatment options, where dysregulated Notch signaling has been implicated in tumor progression and therapeutic resistance. CB-103, a first-in-class inhibitor of the Notch transcriptional activation complex, was selected as a lead structure for the development of new analogues with improved properties suitable for radiolabeling with the short-lived radionuclide carbon-11 (11C).

To support radiolabeling strategies, a ligand-free Cu(OH)₂-catalyzed methoxylation methodology for aryl halides was developed and investigated, providing access to methoxy-functionalized aromatic systems relevant for 11C radiochemistry. In parallel, a three-step, one-pot synthetic strategy toward unsymmetrical 1,1-diarylalkenes was explored to expand the accessible structural diversity of the compound library.

The thesis further investigates medetomidine-inspired diaryl ethers as potential antifouling agents targeting octopamine receptors in barnacle larvae. A diverse amphiphilic diaryl ether library was synthesized and evaluated in biological assays, including receptor-based screening and exploratory antibacterial and antifungal profiling through EU-OPENSCREEN collaborations.

Preliminary radiolabeling studies, in vitro assays, and in vivo evaluations of a selected compound were additionally performed to assess its suitability for molecular imaging applications.

Overall, this work demonstrates how small-molecule scaffold design can be applied across multiple biological systems and highlights the versatility of diaryl-based pharmacophores in medicinal chemistry, molecular imaging, and antifouling research. The findings contribute to new synthetic methodologies, expand the chemical space surrounding CB-103 and medetomidine analogues, and provide a foundation for future optimization of multifunctional bioactive compounds.

Supervisory Committee

• Professor Jørn H. Hansen, Department of Chemistry, UiT  (Main Supervisor)
• Dr. Sindhu Kancherla, Department of Chemistry, UiT
• Associate Professor II Angel Moldes-Anaya, Preclinical PET Core Facility (PETCore), UiT/UNN.
• Researcher Mathias Kranz, Department of Medical Biology, UiT.

Evaluation Committee

• 1st Opponent: Professor Artur Manuel Soares Silva, Department of Chemistry, University of Aveiro, Portugal.
• 2nd Opponent: Associate Professor Odd Reidar Gautun, Department of Chemistry and Biomedical Science, Norwegian University of Science and Technology (NTNU), Trondheim, Norway
• Internal member and leader of the committee: Associate Professor Kristine Bondo Pedersen, Department of Chemistry, UiT, Norway

Streaming

The Trial Lecture and Thesis Defense will be streamed via Panopto:

Trial Lecture (10:15 - 11:15)
Watch the Trial Lecture

Thesis Defense (12:15 - 15:00)
Watch the Thesis Defense

Thesis

The thesis is available in Munin:

View the thesis in Munin