PhD Scientific Days 2022

Pharmaceutical Sciences III. (Poster discussion will take place on the terrace of the room during the Coffee Break)

Synthesis and Characterization of Novel Quinoline Photoremovable Protecting Groups

Előadó neve

Kontra, Bence, MSc

Előadó munkahelye

Semmelweis University, Department of Organic Chemistry, Budapest

Előadó telefonszáma

+36202862500

Előadó e-mail címe

kontrabence@gmail.com

Az előadás címe

Synthesis and Characterization of Novel Quinoline Photoremovable Protecting Groups

Szerző(k) neve és munkahelye

András Karajos 1, Bence Kontra 1,2, Tekla Abonyi 1, Attila Csomos 3,4, Ervin Kovács 5, Zoltán Mucsi 3,6 Petra Dunkel 1
1 Department of Organic Chemistry, Semmelweis University, H-1092 Hőgyes Endre utca 7, Budapest
2 BrainVision Center, H-1096 Vendel utca 11, Budapest
3 Department of Chemistry, Femtonics Ltd., H-1094 Tűzoltó utca 59, Budapest
4 Hevesy György PhD School of Chemistry, ELTE, H-1117 Pázmány Péter stny. 1/A, Budapest
5 Institute of Materials and Environmental Chemistry, Research Centre for Natural Sciences, H-1117 Magyar tudósok körútja 2, Budapest
6 Institute of Chemistry, University of Miskolc, H-3515 Egyetem út 1, Miskolc

Bemutatás módja

Poszter

Szekció

Pharmaceutical Sciences III. (Poster discussion will take place on the terrace of the room during the Coffee Break)

Language of the presentation

English

Preferred session

Pharmaceutical Sciences

Összefoglaló szövege

Introduction: Photoremovable protecting groups (PPGs) could be used for the temporary inactivation of the biological activity of various substrates. The activity could be restored with high spatiotemporal precision with light irradiation as a bioorthogonal trigger. Since the first examples described in the 1970s, PPGs have found widespread application for studying dynamic biological processes, and as drug delivery systems[1]. Depending on their application, PPGs should comply with several criteria, including efficient removal via photoexcitation, as well as a reasonable solubility in the (biological) medium. Novel chemical probes are continuously developed to address unmet needs in terms of physicochemical or photochemical characteristics/performance.
Aims: We have set out to study two structural modifications of the previously disclosed 8-DMAQ scaffold[2]. On the one hand, we planned to introduce hydrophilic groups to improve their solubility. On the other hand, we attempted to improve the efficiency of their removal, and red shift their absorption maxima, by synthetizing derivatives with a more rigid side chain.
Method: The novel derivatives were prepared by a multi-step sequence based on literature pathways, using palladium-catalyzed coupling or alkylation reactions as the key synthetic steps. As model substrate, acetic acid was used via an ester linkage. The probes were characterized by their UV/VIS absorption, aqueous solubility, hydrolytic stability, and photolysis (measured with HPLC monitoring).
Results: A small set of novel quinoline derivatives with hydrophilic side chains were prepared, using different approaches, as necessary. Introduction of rigid side chains was addressed in position 6 and 7 of the quinoline scaffold, using de novo ring synthesis. In this synthetic pathway, the amination and oxidation steps proved to be challenging.
Conclusion: Synthetic pathways were developed for novel, modified quinoline PPGs. Based on the results of the solubility and photolysis studies, we plan to use the most efficient probes for preparing the caged version of neurotransmitters for biological studies.
Funding: National Research, Development and Innovation Office (NKFIH) grant number SNN 135825, ÚNKP-20-5 New National Excellence Program of the Ministry of Innovation and Technology
[1]Cancers 2021, 13, 3237; [2]Org. Lett. 2012, 14, 6366-6369

University and Doctoral School

Semmelweis University, Doctoral School of Pharmaceutical Sciences

Supervisor

Dr. Petra Dunkel

Publication of my abstract

I do not give consent to the publication of my abstract on the website of the congress.

Kind

Szabad

Status

elfogadva

Accepted presentation method

poszter

Előadás fájl jóváhagyás

nem rendelkezett róla

Előadó

6904

Start

13:20

End

13:25

Authors (legacy)

András Karajos 1, Bence Kontra 1,2, Tekla Abonyi 1, Attila Csomos 3,4, Ervin Kovács 5, Zoltán Mucsi 3,6 Petra Dunkel 1
1 Department of Organic Chemistry, Semmelweis University, H-1092 Hőgyes Endre utca 7, Budapest
2 BrainVision Center, H-1096 Vendel utca 11, Budapest
3 Department of Chemistry, Femtonics Ltd., H-1094 Tűzoltó utca 59, Budapest
4 Hevesy György PhD School of Chemistry, ELTE, H-1117 Pázmány Péter stny. 1/A, Budapest
5 Institute of Materials and Environmental Chemistry, Research Centre for Natural Sciences, H-1117 Magyar tudósok körútja 2, Budapest
6 Institute of Chemistry, University of Miskolc, H-3515 Egyetem út 1, Miskolc