Disputas - Master of Science Alexandra Kondratieva

Master of Science Alexandra Kondratieva will Wednesday June 26th, 2024, at 12:15 hold her disputas for the PhD degree in Science. The title of her thesis is:

"Exploring fluorination in MBL inhibitor design"


Antimicrobial resistance (AMR) achieved through, among others, β-lactamase activity, remains an ongoing challenge for the treatment of infections caused by antibiotic-resistant pathogens. Metallo-β-lactamase (MBL)-expressing bacteria, resistant to most β-lactam antibiotics, are of growing clinical relevance with currently no approved treatment options available. The most common approaches to combating AMR include the modification of existing compounds or the development of new drugs and inhibitors. Alternative strategies are also being explored, including novel drug delivery systems. Recently, an approach based on exploiting the ability of MBLs to hydrolyze β-lactams has been investigated using cephalosporin prodrugs. The reported conjugates consisted of aromatic thiol-based MBL inhibitors linked to a cephalosporin scaffold that was designed to release the inhibitors upon enzymatic hydrolysis.

The goal of the current work was to extend the concept of thiol-releasing conjugates to aliphatic thiolbased MBL inhibitors, as aliphatic thiols have been described to lack the required leaving group properties. The work is based on the hypothesis that fluorination in the vicinity of the thiol moiety can be used as a tool in the design of aliphatic thiol-releasing conjugates.

Thus, the initial focus was on designing fluorinated captopril analogues, exhibiting inhibitory activity against relevant MBLs, and investigating the influence of fluorination on their inhibitory effect. A library of fluorinated thiols, of which several exhibited IC50 values in the low micromolar region against NDM-1, was developed. Furthermore, the use of fluorinated inhibitors as probes for NMR-based binding studies was demonstrated on a representative compound.

Evaluation committee:

  • Professor Dr. Jörg Rademan, Freie University, Germany (1. Opponent)
  • Associate Professor Dr. Anders Vik, UiO, Norway (2. Opponent)
  • Post. Doc Torsha Moitra, Department of Chemistry, UiT (intern member and leader of the committee)

Streaming site:

The disputas and trial lecture will be streamed from these sites:
Disputas (12:15 - 15:00)
Trial Lecture (10:15 - 11:00)


The thesis is available at Munin here.

When: 26.06.24 at 12.15–15.00
Where: Auditorium 1.022, Teknologibygget
Location / Campus: Digital, Tromsø
Target group: Employees, Students, Guests, Invited, Unit
Contact: Helge Ravn
E-mail: helge.m.ravn@uit.no
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