News

Discovery of a novel method for characterization of insulin sensitivity

Despite extensive research efforts, very few markers are used in clinics for the diagnosis of type 2 diabetes mellitus. While fatty acid intermediates have been studied in diabetes patients and experimental models of insulin resistance, none of these markers have been successfully translated into clinical practice.

Authors from the Latvian Institute of Organic Synthesis show that a blunted decrease in long-chain acylcarnitine plasma concentrations during the glucose tolerance test is associated with muscle-specific insulin resistance, while postprandial changes in plasma FFA levels reflect adipose tissue insulin sensitivity. Authors propose that implementation of FFAs and long-chain acylcarnitine measurements would provide multiple clinical benefits. This diagnostic approach would provide novel possibilities to characterize tissue-specific insulin resistance during diabetes progression and intervention (both lifestyle changes and pharmacotherapy).

The research has been published in Frontiers in Endocrinology (IF=3.634):

E. Makarova, M. Makrecka-Kuka, K. Vilks, Kristine Volska, Eduards Sevostjanovs, Solveiga Grinberga, Olga Zarkova-Malkova, Maija Dambrova and Edgars Liepinsh
Decreases in Circulating Concentrations of Long-Chain Acylcarnitines and Free Fatty Acids During the Glucose Tolerance Test Represent Tissue-Specific Insulin Sensitivity
Front. Endocrinol., 2019, DOI: 10.3389/fendo.2019.00870

fendo-10-00870-g006

 

New studies on selenocystine peptides

Dr. Pavel Arsenyan group showed a new approach for the generation of selenocysteinyl electrophile by weak Lewis acids or oxidants. The elaborated protocol allows the construction of phenylindeno[1,2‐ c ]chromene moiety in 5‐ endo‐dig /6‐ endo‐dig cascade reactions. This method is published in the European Journal of Organic Chemistry (IF 3.029):

Sindija Lapcinska, Pavel Arsenyan.
Selenocystine peptides performance in 5‐endo‐dig reactions.
Eur. J. Org. Chem., 2020, DOI: 10.1002/ejoc.201901548

Arsenyan_Eur.J.Org.Chem_2020-2

The research was supported by Latvian Institute of Organic Synthesis internal student grant IG-2018-06.

Studies on carbonic anhydrases inhibitors

Continuing studies in the field of carbonic anhydrases (CA) inhibitors, professors R. Žalubovskis’ (LIOS) and Claudiu T. Supuran’s groups published an article in the Journal of Enzyme Inhibition and Medicinal Chemistry (IF=4.027, 2018).  Authors described the synthesis of a new series of homosulfocoumarins and investigated for the inhibition of four physiologically relevant CA isoforms –  the human (h) hCA I, II, IX and XII.

Pustenko, A., Nocentini, A., Balašova, A., Alafeefy, A., Krasavin, M., Žalubovskis, R., Supuran, C.T.
Aryl derivatives of 3H-1,2-benzoxathiepine 2,2-dioxide as carbonic anhydrase inhibitors
J. Enzyme Inhib. Med. Chem. 2020, 35, p. 245-254, https://doi.org/10.1080/14756366.2019.1695795

The research was supported by ERA.Net RUS plus joint programme project THIOREDIN (State Education Development Agency of Republic of Latvia) [grant number RUS_ST2017-309] and the Russian Foundation for Basic Research [grant number 18–515-76001].

Research in the field of new antivirulence drugs

Studies of enzyme Sortase A inhibitors by prof. Jaudzems group (Laboratory of Physical Organic Chemistry) and scientists from Latvian Biomedical Research and Study Centre has been published in the ACS Infectious Diseases (IF  4.911, 2018):

Kristaps Jaudzems, Viktorija Kurbatska, Atis Jēkabsons, Raitis Bobrovs, Zhanna Rudevica, Ainars Leonchiks.
Targeting Bacterial Sortase A with Covalent Inhibitors: 27 New Starting Points for Structure-Based Hit-to-Lead Optimization
ACS Infect. Dis. 2019,  DOI: 10.1021/acsinfecdis.9b00265

Enzyme sortase A has become an attractive target for the development of new antivirulence drugs against Gram-positive infections. 27 compounds as covalent inhibitors of Sortase A has been identified. These compounds have a potential to be developed into broad spectrum antivirulence agents.

New research in the field of traumatic brain injury

Research in the field of traumatic brain injury by Laboratory of Pharmaceutical Pharmacology (LIOS) and scientists from University Hospital Würzburg (Germany) and  Institute for Stroke and Dementia Research (Germany) has been published in the Journal of Neurotrauma (IF  3.754, 2018):

Liga Zvejniece, Gundega Stelfa, Edijs Vavers, Einars Kupats, Janis Kuka, Baiba Svalbe, Baiba Zvejniece, Christiane Albert-Weissenberger, Anna-Leena Sirén, Nikolaus Plesnila, and Maija Dambrova.
Skull Fractures Induce Neuroinflammation and Worsen Outcomes after Closed Head Injury in Mice.
Journal of Neurotrauma 2019, DOI: 10.1089/neu.2019.6524
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This study was supported by the framework of the EU-ERA-NET NEURON project CnsAflame.

 

Networking for excellence in functional pharmacology

On November 11 (2019), Latvian Institute of Organic Synthesis (LIOS) started Horizon 2020 project “Networking for excellence in functional pharmacology to study the role of fatty acid metabolism in neurological disorders” (FAT4BRAIN).

The FAT4BRAIN project is a cooperation between LIOS and world-leading partners in translational neuropharmacology (Uppsala University, Sweden), metabolism and neuropsychiatric imaging research (Eberhard Karls University Tuebingen, Germany) as well as innovative mitochondria research (Oroboros Instruments, Austria).

During the project, partners are going to establish a network of excellence focused on the pivotal and common role of fatty acid metabolism in the development of neurological disorders, a topic of highest biomedical and societal concern.

The FAT4BRAIN kick-off meeting was held from November 7th to 8th in LIOS. The project coordinator is prof. Maija Dambrova (LIOS).

F4B_Kick-off_08.11.2019

Identified a new lead compound for anticancer therapy

Research of Prof. R. Žalubovskis group (LIOS) and scientists from Serbia (Institute for Biological Research “Sinisa Stankovic”; Institute of Nuclear Sciences VINCA ) and Russia (Saint Petersburg State University) has been published in European Journal of Medicinal Chemistry (IF  4.833, 2018) on new  thioredoxin reductase 1 (TrxR1) inhibitors.  Studies identified DVD-445 as a new lead compound for anticancer therapy.

ejmech_111580_fx1_ga_wc_pdf

Mirna Jovanović, Daniil Zhukovsky, Ana Podolski-Renić, Ilona Domračeva, Raivis Žalubovskis, Milan Senćanski, Sanja Glišić, Vladimir Sharoyko, TatianaTennikova, Dmitry Dar’in, Milica Pešić, Mikhail Krasavin.
Novel electrophilic amides amenable by the Ugi reaction perturb thioredoxin system via thioredoxin reductase 1 (TrxR1) inhibition: Identification of DVD-445 as a new lead compound for anticancer therapy.
Eur. J. Med. Chem. 181, 2019, 111580, DOI: 10.1016/j.ejmech.2019.111580

The research was supported by the Russian Foundation for Basic Research (project grant 18–515-76001, Ministry of Education, Science and Technological Development of the Republic Serbia (project III41031), ERA.Net RUS plus joint program grant RUS_ST2017-309 and State Education Development Agency of Republic of Latvia (“THIOREDIN”). This work was also supported by a Short-Term Scientific Mission (STSM) Grant from COST Action CA17104 “New diagnostic and therapeutic tools against multidrug resistant tumors” and European Cooperation in Science and Technology.

New studies in the field of new RNA-binders

Research on the synthesis and RNA-binding properties of extended nucleobases for triplex-forming peptide nucleic acids by Dr. Martins Katkevics group (Latvian Institute of Organic Synthesis) and professor Eriks Rozners lab (Binghamton University) has been published in the Journal of Organic Chemistry (IF 4.745, 2018).

Ilze Kumpina, Nikita Brodyagin, James A. MacKay, Scott D. Kennedy, Martins Katkevics, Eriks Rozners.
Synthesis and RNA-Binding Properties of Extended Nucleobases for Triplex-Forming Peptide Nucleic Acids.
J. Org. Chem. 2019, DOI:  10.1021/acs.joc.9b01133

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This work was supported by the Latvian Institute of Organic Synthesis, internal research fund IG-2018-04, and the U.S. National Science Foundation grants CHE-1708761 to E.R. and CHE-1708699 to J.A.M.

New research in the field of purely organic luminescent materials

Prof. Suna (LIOS) group recently started a new research direction in the field of purely organic luminescent materials. The latest research on the design of aggregation induced emission luminogens is published in the journal Chemical Communications (Impact factor: 6.164):

Kaspars Leduskrasts,  Artis Kinens, Edgars Suna
Cation–π interactions secure aggregation induced emission of planar organic luminophores.
Chem. Commun., 2019, DOI: 10.1039/C9CC06829E

The research has showed that the use of non-covalent intermolecular π+–π interactions between quaternary pyridinium or imidazolium cations and aromatic π systems is an efficient approach to achieve AIE in planar purely organic luminophores.

Alliance4Life Formalizes its Existence

All4Life

Today, on 4th October 2019, the founding members of the Alliance4Life gathered at Vilnius University and signed the Memorandum of Understanding, which formalizes the alliance as a permanent structure. The Alliance4Life connects progressive life science institutions from Central and Eastern Europe. The mission of the Alliance4Life shall be to support and strengthen European research excellence and the impact of scientific research on society, human health, and quality of life. The signing of the memorandum is the crown jewel of Alliance4Life´s achievements during the past two years of its existence. It symbolizes the partners’ commitment to make this alliance a long lasting one, for the benefit of the members and the whole region.

The formal existence of the Alliance4Life is in line with the current shift of the EU research policy towards a more sensitive approach to research and innovation needs of the Central and Eastern European countries. The Alliance4Life´s voice has been heard also during the new Horizon Europe negotiations, and surely will be listened to in the future. Alliance4Life intends to become a role model for institutions in less performing regions and to serve as a hub of excellence, inspiring others.

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The Alliance4Life started two years ago as a project initiated by CEITEC Masaryk University with the clear mission to help close the innovation gap. Benchmarking exercises served as a starting point for development strategies for all seven focus groups – science evaluation, ethics and integrity, human resources and mobility, grants and funding, core facilities, knowledge and technology transfer, and science communication. The project enabled the members to gather for joint trainings and to develop best practice inventory, representing an enormous value for the members. During this meeting hosted by Vilnius University, all members confirmed that progress was made and a solid strategy was developed to be implemented in the years to come!

Masaryk University (CEITEC – Central European Institute of Technology) CZ
St. Anne’s University Hospital Brno (ICRC – International Clinical Research Center) CZ
Biomedical Research Center of the Slovak Academy of Sciences SK
Medical University of Lodz PL
University of Zagreb School of Medicine HR
University of Tartu EE
Vilnius University – Faculty of Medicine LT
Latvian Institute of Organic Synthesis LV
University of Ljubljana SI
SU Semmelweis University HU
EU-FLAG_cmyk_304dpi_small The project “Alliance for Life Sciences: Closing Research and Innovation Divide in
the European Union” received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement No. 779303.