3 Bachelor's thesis finished and 2 new ERASMUS student in

One thing that makes the days always busy at this time of year (including the end of the previous year) is the Bachelor's thesis in Pharmacy and their supervision. I have yearly about 3 student's for which I give the titles and then their write about. The schedule is tight, the thesis needs to be accepted in very early January, since the students will give their seminar presentations of their topic in late January, this year the presentations were already during this week. This year we had the following topics:

1. Valproic acid - something more than an antiepileptic drug?

2. Choline esterases as drug targets and drug metabolizing enzymes

3. Metabolism of amino acids in cancer - novel targets for drug development?

All the students of this year did a great job and they were really self-orientated and easy to supervise, so well done, Lura, Suvi, and Elisa! And now I have few weeks time to figure out the new titles for the next years' students, so in that perspective, the students have the whole year time to write the thesis, but in most cases, they usually start to work on it October earliest! 😊

We have also received new ERASMUS student to work in our group until next May. The plan is to synthesize couple of prodrugs under and then study their bionconversion and release rate of the parent drugs in different biological media, such as human plasma. So welcome Ines and Catarina!

A second paper for this year out!

We have had a superior start for this year, a second paper already out! Well, to tell the truth this is all about hard work last year, so once again, thank you all the co-authors for your great contribution! In this paper called "Comparison of Experimental Strategies to Study l-Type Amino Acid Transporter 1 (LAT1) Utilization by Ligands" (link for the publication, open access), we have compared different kind of methods how transporter-utilizing compounds can be studied and what is needed to be taken into account when interpretting these results. Of course we utilized LAT1 as an example transporter and this was submitted as a part of our special issue in Molecules (link to the special issue). To this study, a Ph.D. student Mahmoud from Pharos University of Alexandria (Egypt) participated with his great contribution, when he visited us as an ERASMUS student in 2018. So, it took a while until we got everything wrapped into this nice paper! 😁

SBBN Virtual meeting

There will be an interesting mini-symposium this Friday online, come to see the hot topics around brain drug delivery! 😀 Originally, we planned to have this in real-life, but COVID-19 is still bugging us...

 

DRA online symposium , 14/01/2022 10:00–16:45 (CET)

4'th Scandinavian Blood-brain Barrier Network Symposium

University of Copenhagen, Faculty of Health and Medical Sciences, PharmaSchool

 

The symposium is free of charge and open for attendance by all interested parties.

Organizing Committee: Margareta Hammarlund-Udenaes, Kristiina Huttunen,

Christoffer Bundgaard & Birger Brodin

Programme

10:00               Welcome, introduction of the program of the day and the network

                        Org Committee/ Birger Brodin, Department of Pharmacy, University of Copenhagen

10:15               Pharmacoproteomics of the CNS barriers: A fingerpost for the drug discovery and development
 Tetsuya Terasaki, Research Director, School of Pharmacy, University of Eastern Finland

11:15               CNS uptake of prodrugs via the amino acid transporter LAT-1, possibilities and pitfalls
 Kristiina Huttunen, Group leader, University of Eastern Finland

12:00              Lunchbreak

13:00              Two-photon imaging studies of uptake of nanoconstructs in the brain vasculature                                  Martin Lauritzen, Professor, Department of Neuroscience, University of Copenhagen

14:00              Transcytosis in the brain capillary endothelium studied in vitro                                                                Morten Schallburg Nielsen, Department of Biomedicine, University of Aarhus

14:45              Coffee break

15:00             The combinatory mapping approach and it's use in brain drug delivery studies                                          Irena Loryan, Group leader, Department of Pharmacy, University of Uppsala

15:45             Peptide drug delivery to the brain:  An industry perspective                                                                   Stephen Buckley, Director, Novo Nordisk

16:30             Final comments from the Organizing Committee

 

Zoom link: https://ucph-ku.zoom.us/j/69729192863?pwd=Tm1mQ1RlNGFzK1pCVjFCODdFSEFXZz09
Meeting ID: 697 2919 2863
Passcode: 742687

New paper for the New Year

The Year 2022 started effectively, we already have our first paper for this year out! 😀 This paper is a continuation of our collaborative metformin project, in which we have designed and synthesized different kind of metformin analogues, and then studied their cellular uptake, the uptake mechanisms (what transporters are carrying them) and if they would have better cytotoxic effects in cancer cells than metformin itself and by which mechanism. We found that the sulfonamide derivative of metformin with long fatty acid tail attached to the benzyl ring had increased cellular accumulation in human breast cancer cells (MCF-7 and MDA-MB-231 lines) resulting in induced early and late apoptosis due to the cell cycle arrest in the G0/G1 and G2/M phases. This compound also induced intracellular reactive oxygen species (ROS) production and reduced mitochondrial membrane potential, which can ultimately lead to mitochondrial dysfunction and activation of the mitochondrial-associated apoptosis-signaling pathway. So in overall, this compound seems to be one of the best metformin analogues we have had so far, which guides us in the structural design of new analogues and encourages to continue to study this compound even further. However, you can read more about the present results here (not open access, unfortunately):

Sulfonamide metformin derivatives induce mitochondrial-associated apoptosis and cell cycle arrest in breast cancer cells (link for the publication)

And greatest thanks of this publication goes to the first and corresponding author Magdalena! Job well done! And now since this paper is out, she has already submitted another manuscript related to the anti-coagulation properties of these compounds. Let's hope I can have something more to write about this topic during the upcoming spring! 😀