Disputas - Master of Science Aya Ismael

Master of Science Aya Ismael will Monday October 26th at 12:15 PM publically defend her thesis for the PhD degree in Science.

 Title of the thesis:

"Method development towards synthesis of carbapenemase inhibitors"

Popular scientific abstract:

 "Carbapenemases are enzymes that are known to hydrolyze last resort b-lactam antibiotics, which are used for treatment of bacterial infections. In order to overcome the hydrolytic activity of these enzymes, combination therapy of a b-lactam with a b-lactamase inhibitor have been clinically successful. Due to emerging resistance towards some of the clinically applied combinations, there is an urgent need to find new effective inhibitors that could potentially reach clinical use. The approach targeted in this thesis is to design new inhibitors against two types of carbapenemases (VIM-2 & OXA-48) and to develop synthetic methods in order to synthesize the potent inhibitors. In this thesis I discuss a fragment-based drug discovery (FBDD) study that we applied to design a new line of inhibitors against the clinically relevant SBL OXA-48. We synthesized a fragment library of substituted benzoic acids. The fragments were tested for their inhibition activity and crystal structures of OXA-48/fragment complexes were obtained. The structural information was used to in silico design overlay structures of overlapping fragment binding in two adjacent binding pockets (inn (R2) and out (R1) pocket). The best overlay structures were synthesized via a synthetic strategy based on selective Suzuki-Miyaura coupling that gave us access to a small library of unsymmetrically 3,5-disubstituted benzoic acids. The 3,5-disubstituted benzoic acids showed good inhibition and crystal structures in complex with OXA-48 were obtained.

I also devised an approach to synthesize 2-aroylbenzoic acids and derivatives, which have previously shown activity against the clinically relevant MBL VIM-2. In this thesis I present the developed synthetic strategy towards 2-aroylbenzoic acids and show the possibility of obtaining them in moderate to high yields via carbonylative Suzuki coupling using CO in a safe fashion. I also expanded our synthetic strategy to include testing of a wide range of sustainable solvents for better reactivity within carbonylative coupling reactions. The awareness of the environmental concerns also directed the research to contribute to greener chemistry practices. Overall, many of the sustainable solvents examined in this work led to good yields in some of the test reactions and showed excellent tolerance under all tested conditions. The synthetic strategies introduced in this thesis are considered to be a starting point to develop a synthetic approach towards a wide range of potent inhibitors against carbapenemases."


The thesis is published in Munin and is available at: https://hdl.handle.net/10037/19594


  • Associate Professor Annette Bayer, Department of Chemistry, UiT (main supervisor)
  • Professor Hanna-Kirsti Schrøder Leiros, Department of Chemistry, UiT
  • Doctor Johan Isaksson, Department of Chemistry, UiT

Evaluation committee:

  • Professor Nina Kann, Chalmers Tekniska Högskola, Sweden  (first opponent)
  • Professor Bård Helge Hoff, Department of Chemistry, NTNU (second opponent)
  • Dr. Vijayaragavan Elumalai, Department of Chemistry, UiT(internal member and leader of the commitee)

Reserve member : Dr. Yvonne Piotrowski, Department of Chemistry, UiT

Professor Nina Kann will participate remotely to the defence.

Leader of the public defense:
The leader of the public defense is Professor Alfred Hanssen, Vice dean for Innovation, UiT.

Opposition ex auditorio:
If you have any questions for the candidate during the public defence, please send an e-mail to the leader of the public defence. They will announce the questions during the defence.


Trial lecture:

The trial lecture is held Monday October 26th at 10:15 AM in the same auditorium.

Title of the trial lecture: «Replacing palladium in cross-couplings: methods, mechanism and sustainability»



The defense and trial lecture will be streamed via Mediasite:



UiT follows the national guidelines regarding infection control. A maximum of 20 people are allowed in the auditorium during the defence, as long as everybody keeps a distance of 1 meter at all times.

Få utskriftsvennlig versjon ved å trykke på denne
Når: 26. oktober 2020 kl. 12.15–15.00
Hvor: Auditorium 1.022, Teknologibygget
Studiested: Digitalt, Tromsø
Målgruppe: ansatte, Studenter, gjester / eksterne, inviterte
Kontakt: Marie-Josée Haglund Halsør