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Eleganine A total synthesis

Continuing studies on eleganine A total synthesis, Dr. Smits (Laboratory of CNS Active Compounds) and Dr. Zemribo elaborated a new synthetic approach towards the core of a structurally unique cytotoxic indole alkaloid eleganine A.

Graphical abstract: Stereoselective synthesis of an eleganine A core

The research is published in the Organic & Biomolecular Chemistry (IF= 3.490, 2019):

Gints Smits, Ronalds Zemribo
Stereoselective synthesis of an eleganine A core
Org. Biomol. Chem., 2020,18, 4566-4568, doi: 10.1039/D0OB00939C

President of Latvia Egils Levits visited the Latvian Institute of Organic Synthesis

On 29 June, President of Latvia Egils Levits visited the Latvian Institute of Organic Synthesis (LIOS) to receive Solomon Hiller Medal, an award honouring scientific achievements and contribution to the development of science.

During the visit, President Levits toured Laboratory of Large-Scale Synthesis, Laboratory of Pharmaceutical Pharmacology, Laboratory of Advanced Technologies for Organic Synthesis and Laboratory of Physical Organic Chemistry. Egils Levits then met with the administration and members of Scientific Board to discuss the role of independent institutes in a national scientific framework, support to scientific excellence at the national level, national Covid-19 research programme and financing of science in Latvia.

Photo: Ilmārs Znotiņš, Chancery of the President of Latvia

Address of the President of Latvia Egils Levits at the Latvian Institute of Organic Synthesis

Dear esteemed scientists,

Dear family of the Organic Synthesis Institute,

I am happy to visit your institute and flattered to witness how mankind’s newest breakthroughs and knowledge become products that people here in Latvia and the whole wide world will appreciate. You belong to the scientific elite of Latvia and we need your organic synthesis innovations now more than ever before.

The world has been hit hard by Covid-19, and it will probably never look the same. Pandemic has changed the world. We have successfully overcome the unexpected challenges. This summer, right now, we are in much better situation than many other countries. And only because we followed warnings of scientists. Instead of panicking, turning a blind eye on them, we did what scientists told us to do, and here we are. We have to believe science. But virus is still out there. We, the people of Latvia, will have to continue looking up to our scientists for guidance.

Scientists of Latvian Biomedical Research and Study Centre, Institute of Solid State Physics, University of Latvia, Riga Technical University and Organic Synthesis Institute have decided to collaborate on national research programme project ‘New methods for treatment and prevention of Coronavirus and effects of infections caused by it’. Once approved, this project will enable scientists to develop a unique testing platform for assessing the efficiency of new and repurposed active substances against SARS-CoV-2 virus. Latvia and the whole world badly need these new solutions and I truly hope that this project and other socially-significant projects will get the needed support.

Dear friends and colleagues,

Science is not easy. Most people only see the amazing fruits of scientific labour – the astonishing innovations. Very few know how many extra manhours, days and years of relentless and hard work have gone into these inventions, often without tangible results, especially in fundamental sciences. We often do not know what we wight stumble upon, yet quite often results are not only applicable, but also ground-breaking and very innovative. So, let me use this opportunity to underline the role of fundamental sciences in raising the public image of science and bringing scientific policy forward. Dear experts of the Latvian Institute of Organic Synthesis, we do acknowledge and appreciate your work. You are not forgotten. We constantly refer to you, your achievements, accomplishments and selfless dedication. And I will do my best to advocate for increased scientific funding because our future relies on it. Your success is the success of the whole Latvia. You help promote Latvia’s name globally and also are responsible for major contribution to our national economy. We all want to become a knowledge society. There just is no other way. We want to become a welfare state and we to do it together with you and other exceptional scientists.

One of the best examples of what years of dedication and excellence can achieve is the new active substance that is a candidate for treatment of cardiovascular diseases. It can save lives. A study conducted last year showed very promising results. Now we just have to wait for the decision on what will happen with this first drug candidate next.

LOSI is a brand well-known in Europe. Your scientists are highly revered around the world. Latvian Institute of Organic Synthesis has successfully participated in various European Commission framework programme activities and projects both with local industries and international companies. This means that you are competitive, inventive and capable of producing European and world class research.

I am very grateful and extremely proud about what you have done for our country. Science is one of the priorities of Latvia and my presidency. We appreciate what you are doing for our people and for our common future.

I wish you success in your scientific endeavours, many great discoveries and, of course, plenty of scientific excellence!

Source of information: Chancery of the President of Latvia

 

Research in the field of β-lactam antibacterials

Research against resistance to β-lactam antibacterials by Dr. Trapencieris group and colleagues from the University of Oxford, University of Leeds and Jacobs University Bremen has been published in the Biomolecules (IF= 4.082, 2019): 

Lang P. A., Parkova A., Leissing T. M., Calvopiña K., Cain R., Krajnc A., Panduwawala T.D., Philippe J., Fishwick C. W. G.,Trapencieris P, Page M. G. P., Schofield C. J. , Brem J.
Bicyclic Boronates as Potent Inhibitors of AmpC, the Class C β-Lactamase from Escherichia coli.
Biomolecules 2020, 10(6), 899; doi: 10.3390/biom1006089

New article in the field of natural product synthesis

Dr. Dace Rasiņa et.al. (Organic Synthesis Methodology group) have published a concise bioinspired semisynthesis of rumphellaones A–C and their C-8 epimers from β-caryophyllene in the Journal of Natural Products (IF=4.257, 2019).

Stakanovs G., Mishnev A., Rasina D.*, Jirgensons A.
A Concise Bioinspired Semisynthesis of Rumphellaones A–C and Their C-8 Epimers from β-Caryophyllene.  J. Nat. Prod. 2020, doi: 10.1021/acs.jnatprod.0c00403

This is the first semisynthetic route toward rumphellaones B and C and their C-8 epimers as well as the shortest synthesis of rumphellaone A and its C-8 epimer from the most accessible sesquiterpene, β-caryophyllene.

Published improved method for the preparation of nonyl acridine orange analogues and utilization in detection of cardiolipin

Dr. Pavel Arsenyan group elaborated a fast and convenient methodology for the preparation of 10-nonyl acridine orange (NAO) and its silyl analogues to improve their photo-physical properties for the detection and quantification of cardiolipin (CL). This study is published in the New Journal of Chemistry (IF= 3.069, 2019):

Dimitrijevs P., Domracheva I., Arsenyan P.*
Improved method for the preparation of nonyl acridine orange analogues and utilization in detection of cardiolipin. New J. Chem., 2020, doi: 10.1039/D0NJ02116D

The optimized conditions allow synthesizing NAO analogues in good yield and excellent purity. Authors showed that the introduction of a 3-(trimethylsilyl)propyl moiety improves the dye’s solubility and stability in buffer solution and increases its emission intensity by ≈30% as well. The novel dye can be used for the selective quantification of CL in a liposomal inner mitochondrial membrane model with greater fluorescence intensity and linear slope compared to NAO. The novel silicon-containing NAO analogue has lower cytotoxicity, and is a convenient fluorescent dye for cell staining.

Empagliflozin Protects Cardiac Mitochondrial Fatty Acid Metabolism

Researchers from the Laboratory of Pharmaceutical Pharmacology have shown that empagliflozin treatment preserves mitochondrial fatty acid oxidation in the heart under conditions of chronic lipid overload.

The research was performed within the Horizon 2020 FAT4BRAIN project and published in the journal Cardiovascular Drugs and Therapy (IF=3.367, 2018).

Makrecka-Kuka M., Korzh S., Videja M., Vilks K, Cirule H., Kuka J., Dambrova M., Liepinsh E.   Empagliflozin Protects Cardiac Mitochondrial Fatty Acid Metabolism in a Mouse Model of Diet-Induced Lipid Overload.   Cardiovasc. Drugs. Ther. 2020. doi: 10.1007/s10557-020-06989-9

The antibiotic furagin and its derivatives are isoform-selective human carbonic anhydrase inhibitors

Continuing studies of carbonic anhydrase (CA) inhibitors, professors Raivis Žalubovskis’ (LIOS) and Claudiu T. Supuran’s groups showed that clinically used antibiotic Furagin and its derivatives possess inhibitory activity on human CA. It gives the solid base for investigation of drug repurposing of Furagin for anti-cancer therapy. The research is published in the Journal of Enzyme Inhibition and Medicinal Chemistry (IF=4.027, 2018):

Pustenko, A., Nocentini, A., Gratteri, P., Bonardi, A., Vozny, I., Žalubovskis, R., Supuran, C.T.  The antibiotic furagin and its derivatives are isoform-selective human carbonic anhydrase inhibitors.  J. Enzyme Inhib. Med. Chem. 2020, 35 (1), p. 1011-1020, DOI: 10.1080/14756366.2020.1752201

Furagins

 

 

Research on New Calcium Ion Transport Modulators

Dr. Domracheva et.al. have published studies about novel 4-pyridinio-1,4-dihydropyridine (1,4-DHP) derivatives possessing calcium channel modulating activity.  The antagonist, agonist, and dual-action effect of the 1,4-DHP were evaluated.  The research is published in the journal “Oxidative Medicine and Cellular Longevity” (IF=4.868, 2018).

Ilona Domracheva*, Iveta Kanepe-Lapsa, Reinis Vilskersts, Imanta Bruvere, Egils Bisenieks, Astrida Velena*, Baiba Turovska, Gunars Duburs.
4-Pyridinio-1,4-Dihydropyridines as Calcium Ion Transport Modulators: Antagonist, Agonist, and Dual Action.
Oxid. Med. Cell. Longev. 2020, 2075815, DOI 10.1155/2020/2075815

This research was financially supported by Latvian Council of Science, National Research Programme PUBLIC HEALTH/Biomedicine of the Republic of Latvia, as well as projects NFI/R/2014/051 and INNOVABALT (REGPOT-CT-2013-316149).