Gunars DUBURS

Born: June 12, 1934, Riga, Latvia.

Interests:

• Heterocyclic Chemistry (mainly partially hydrogenated azines: dihydro- (tetrahydro-) pyridines, pyrimidines, polycyclic derivatives) - studies of chemical, physical chemical and biological properties
• Medicinal Chemistry (synthesis and studies of neurotropic, cardiovascular, antioxidative, membrane protective, radioprotective, UV-protective, peptidomimetic, gene transfection agents)

Research in organic chemistry, especially – partially hydrogenated nitrogen and sulfur containing heterocycles, medicinal and food chemistry (antioxidants), drug research (radioprotectors, cardiovascular compounds and neuroprotectors). Scientific articles – 475, 64 patents, 105 authors certificates. Developed and registered 2 original preparations for medicine: antihypertensive, antianginal preparation foridone (riodipine), radioprotector diethone; for agriculture – antioxidant, feed and food stabilizer diludine; proposed preparations for organic analysis.

Education:

• University of Latvia (Faculty of Chemistry), 1957
• Dr.chem. (Candidate of Science in former USSR, Ph.D. in Western countries), Latvian Academy of Sciences, 1961
• Dr.habil.chem. (Doctor of Science in former USSR), Latvian Institute of Organic Synthesis, 1979

Experience:

Latvian Institute of Organic Synthesis -

• Researcher, 1957-1964
• Head of Laboratory, 1965 -
• Deputy Director, 1980 - 2003
• Professor (Organic Chemistry), 1988 -

 

Honours and Awards:

• Corresponding Member, Latvian Academy of Sciences , 1990
• Full Member, Latvian Academy of Sciences , 1992
• Latvian State Prize, 1977
• Latvian Academy of Sciences Gustavs Vanags Prize (in Chemistry), 1984
• Latvian Council of Ministers Prize , 1990
• S.Hiller Medal (Institute of Organic Synthesis), 1991
• Paul Walden Award (Riga Technical University) , 1994
• D.H.Grindel Medal (company ‘Grindex’, Latvia), 1996
• Latvian Cabinet of Ministers Prize, 1999
• Latvian Academy of Sciences and Latvian Patent Office Award, 2000
• Latvian Academy of Sciences Presidium Award, 1970, 1971, 1972, 1980, 1984
• Oswald Schmiedeberg Medal (Tartu University, Tartu, Estonia), 2001
• State Emeritus Scientist, 2002
• Certificate and Golden Medal  of World Intellectual Property Organisation (WIPO) for long-term and highly productive work as inventor, 2006

Professional Activities:

• Member of Scientific Council, Latvian Institute of Organic Synthesis
• Member, Habilitation and Promotion (Chemistry) Council, Faculty of Chemistry, University of Latvia
• Member of Editorial Board for Khimiya Geterotsikl. Soed. (Chemistry of Heterocyclic Compounds), International Journal of Molecular Science, International Journal of Applied Chemistry.

Memberships:

• International Society of Heterocyclic Chemistry
• Latvian Society of Medicinal Chemistry
• Latvian Chemical Society

Plenar lecturer, lecturer, participant of symposiums, conferences, congresses:

• 5th, 6th, 7th FECHEM Conferences on Heterocycles in Bio-organic Chemistry (1988, 1990, 1993)
• 12th International Symposium on Medicinal Chemistry, 1992
• 9th Noordwijkerhout-Camerino symposium "Trends in Drug Research" , 1993
• 14th International Congress of Heterocyclic Chemistry, 1993
• AFMC Intern. Medicinal Chem. Symp. (AIMECS 95), 1995
• The Nobel Forum "HIV-1 Infection of the Brain", 1995
• 11th Intern. Conference on Organic Synthesis, 1996
• 14th Intern. Symposium on Medicinal Chemistry, 1996
• 10th European Symposium on Organic Chemistry, 1997
• 12th Intern. Conference on Organic Synthesis, 1998
• 17th Intern. Congress of Heterocyclic Chemistry, 1999
• 2nd European Congress on Pharmacology,1999
• 16th  Intern. Symposium on Medicinal Chemistry, 2000
• 17th  Intern. Symposium on Medicinal Chemistry, 2002
• 18th  Intern. Symposium on Medicinal Chemistry, 2004
• Delivered lectures at University of Gent (Belgium), Wageningen Agricultural University (The Netherlands), University of Basque Country (Spain), Teikyo University (Japan), Univerisity of Leeds (UK), University of Kuopio (Finland), Institute of Organic and Biochemistry, Prague (Czech Republic).

 

Recent/Representative Publications:

• Tirzite D., Tirzitis G., Vigante B., Duburs G. The effect of some 1,4-dihydropyridine and 1,4-dihydroindeno[1,2-b]pyridine derivatives on glutathione S-transferase activity in vitro. - Biochem. Pharmacol., 1993, vol. 46, N 4, pp.. 773-775.
• Ivanov E.V., Ponomareva T.V., Borisova V.V., Vocvodina T.M., Artamonova E.A., Rusanova O.V., Vetuh V.A., Shubik V.M., Merkushev G.N., Bisenieks E.A., Dubur G.Y., Bokk M.I. The development of radioprotectors-anticancerogens for chronic irradiation. - Intern. J. Radiation Hygiene, 1993, vol. 1, N 1, pp. 39-49.
• Taraban M.B., Kruppa A.I., Polyakov N.E., Leshina T.V., Lusis V., Muceniece D., Duburs G. The mechanisms of the oxidation of NADH analogues. 1. Photochemical oxidation of N-unsubstituted 1,4-dihydropyridines by various acceptors. - J. Photochem. Photobiol. A: Chem., 1993, vol. 73, pp. 151-157.
• Karpova M., Germane S., Cebers G., Pankov O., Klusa V., Duburs G., Bisenieks E. Antiepileptic properties of glutapyrone: novel type derivatives of 1,4-dihydropyridines containing amino acids. - Bull. Exp. Biol. Med., 1993, vol. 116, N 9, pp. 283-285.
• Duburs G., Skrastins I., Kastrone V. Synthesis of polycyclic systems containing dehydropyridine nucleus. - 14th Intern. Congr. of Heterocyclic Chemistry, Aug. 1-6, 1993, Antwerp, Belgium: Abstr. - Antwerp, 1993. - PO3-168.
• Duburs G., Tirzitis G., Bisenieks E. Synthesis and investigation of free radical reaction modulators and development of membranoprotectors. - 9th Noordwijkerhout-Camerino Symp. Trends in Drug Research, May 23-27, 1993, The Netherlands: Abstr, 1993.
• Cekavicus B., Duburs G., Kirule I. Synthesis and antioxidant activity of partly hydrogenated pyridines . - 7th FECHEM Conf. on Heterocycles in Bio-organic Chemistry, Sept. 26-29, 1993, Santiago de Compostela, Spain, 1993. - PO-106.
• Polyakov N.E., Taraban M.B., Kruppa A.I., Avdievich N.I., Mokrushin V.V., Schastnev P.V., Leshina T.V., Lûsis V., Muceniece D., Duburs G. The mechanisms of oxidation of NADH analogues. 3. Stimulated nuclear polarization (SNP) and chemically induced dynamic nuclear polarization (CIDNP) in low magnetic fields in photo-oxidation reactions of 1,4-dihydropyridines with quinones. - J. Photochem. Photobiol. A: Chem., 1993, vol. 74, pp. 75-79.
• Poikans J., Tirzitis G., Bisenieks E., Uldrikis J., Gurevich V.S., Mikhailova I.A., Duburs G. The derivatives of 2,6-dimethyl-1,4-dihydroisonicotinic acid and their antiplatelet properties. - Eur. J. Med. Chem., 1994, vol. 29, pp. 325-328.
• Kazuss E., Sagun E., Tirzitis G., Duburs G. Quenching of singlet oxygen by electrondonating derivatives of 1,4-dihydropyridine . - Chem. Heterocycl. Comp., 1994, N 5, pp. 641-643.
• Makarova N., Koronova Zh., Plotniece A., Tirzite D., Tirzit G., Duburs G. Synthesis of 1,4-dihydropyridine derivatives possessing N-alkylpyridinium in position 4, their affinity to liposome membranes . - Chem. Heterocycl. Comp., 1995, N 8, pp. 1112-1117.
• Stradins J., Baumane L., Gavars R., Vigante B., Duburs G. Free radicals at electrochemical reduction of 3-nitro-1,4-dihydropyridin derivatives . - Chem. Heterocycl. Comp., 1995, N 3, pp. 355-364.
• Duburs G., Klusa V., Bisenieks E., Liepina I., Germane S., Biseniece D., Poikans J. Novel peptidomimetics: focus on cyclic dihydroisonicotinoyl structures containing amino acid moieties. - AFMC Intern. Medicinal Chemistry Symp. (AIMECS 95), Sept. 3-8, 1995, Tokyo, Japan: Progr., Abstr., Handbook, 1995, P. 229.
• Sausins A., Chekavichus B., Duburs G. Methods for the synthesis of 4-pyrazolyl- and 4-pyridyl-5-oxo-1,4,5,7-tetrahydrofuro[3,4-b]pyridines. - Chem. Heterocycl. Comp., 1995, N 7, pp. 966-972.
• Duburs G., Bisenieks E., Germane S., Klusa V., Bleidelis E., Misane I. Nootropic agent . -1994, Patent of Latvia LV 5577 .
• Skrastins I., Vitolina R., Kastrone V., Duburs G. Synthesis and cardiotonic activity of furo[3,4-b]- and difuro[3,4-b,3,4-e]pyridines. - Khim.-Pharm. Zh., 1995, vol. 29, N 5, pp. 31-35.
• Duburs G., Kazuss E., Tirzitis G. NADH model compounds - modulators of cell antioxidants, prooxidants, active oxygen forms and peroxynitrite. - Intern. Conf. New frontiers in cell and molecular biology, Oct. 2-7, 1995, Warsaw, Poland: Progr. a. Abstr, 1995, P. 90.
• Klusa V., Duburs G., Velena A., Svirskis S., Skujins A. Neuro- and myoprotective properties of cerebrocrast and glutapyrone, the novel endogenous ligand-containing dihydropyridines: focus on the mitochondrial effects. - The Nobel Forum HIV-1 infection of the brain: towards a better understanding of the pathogenic events, June 2-4, 1995, Stockholm, Sweden: Abstr, 1995. - S.l.
• Ozols A., Pelcers Yu., Kalme Z., Popelis Yu., Turovskis I., Duburs G. Synthesis and chemical properties of 8-aryl-7-acyl-1,6-dimethyl-6-hydroxy-4-cyano-5,6,7,8-tetrahydro-3(2H)-isoquinolinones and isoquinolinonethiones. - Chem. Heterocycl. Comp., 1996, N 1, pp. 59-66.
• Poikans J., Bisenieks E., Uldrikis J., Klusa V., Germane S., Kemme A., Duburs G. Octahydro derivatives of a novel heterocyclic system benzo[f][1,2]diazepino[5,4,3-c,d]indoles. - Heterocyclic Communications, 1997, vol. 3, N 1, pp. 73-78.
• Velena A., Skujins A., Svirskis S., Bisenieks E., Uldrikis J., Poikans J., Duburs G., Klusa V. Modification of swelling-contraction-aggregation processes in rat muscle mitochondria by the 1,4-dihydropyridines, cerebrocrast und glutapyrone, themselves and in the presence of azidothymidine. - Cell Biochem. Funct., 1997, vol. 15, pp. 211-220.
• Liepina I., Blanco M., Duburs G., Liwo A. Spatial structure of dihydropyridines and similarity of dihydropyridines with some amino acids. -   Mol. Engineering, 1997,  N 7, pp. 401-427.
• Poikans J., Bisenieks E., Uldrikis J., Klusa V., Germane S., Kemme A., Duburs G. Octahydro derivatives of a novel heterocyclic system benzo[f][1,2]diazepino[5,4,3-c,d]indoles. -   Heterocycl. Commun., 1997, vol. 3, N 1, pp. 73-78.
• Misane I., Klusa V., Dambrova M., Germane S., Duburs G., Bisenieks E., Rimoldidni R., Ogren S.O. Atypical neuromodulatory profile of glutapyrone, a representative of a novel "class" of amino-acid containing dipeptide-mimicking 1,4-dihydropyridine (DHP) compounds: in vitro and in vivo studies.- Eur. Neuropharmacol., 1998, N 8, pp. 329-347.
• Krauze A., Popelis J., Duburs G. Efficient regioselective one-pot synthesis of partially hydrogenated thiazolo[3,2-a]pyridines. - Tetrahedron, 1998, vol. 54, pp. 9161-9168.
• Krauze A., Vitolina R., Garaliene V., Klusa V., Duburs G. Search for agents possessing inotropic activity in a series of sulfur analogues of cardiotonic drug Milrinone. - Fundamental Clinical Pharmacol., 1999, vol. 13, Suppl. 1: 2nd Europ. congr. of pharmacology Drugs against disease to improve quality of life: gateway to the 21st century through EPHAR symposia, Bud, 1999. - P. 229s.
• Krauze A., Germane S., Eberlins O., Sturms I., Klusa V., Duburs G. Derivatives of 3-cyano-6-phenyl-4-(3'-pyridyl)- pyridine-2(1H)-thione and their neurotropic activity. - Eur. J. Med. Chem., 1999. - Vol. 34. - P. 301-310.
• Briede J., Daija D., Stivrina M., Duburs G. Effect of Cerebrocrast on the lymphocyte blast transformation activity in normal and streptozotocin-induced diabetic rats. - Cell Biochem. Funct. – 1999, vol. 17, pp. 89-96.
• Briede J., Stivrina M., Bisenieks E., Uldrikis J., Makarova N., Poikans J., Duburs G., Heidemanis K. Antidiabetic drug. - 01.07.1998., PCT/LV98/00005.
• A.Krauze, G.Duburs. Synthesis, dehydration and oxidation of 3-cyano-4,6-diaryl-5-ethoxycarbonyl-6-hydroxypiperidine-2-thiones. - Heterocycl. Commun., 2000, vol.6, N 3, pp. 239-244.
• A.Krauze, G.Duburs. Synthesis and properties of 4,5-trans-4-aryl-3-cyano-6-hydroxy-6-methyl-5-pyridinio-1,4,5,6-tetrahydropiridine-2-thiolates. - Heterocycl. Commun., 2000, vol.6, N 3, pp. 265-270.
• A.Krauze, G.Duburs. Synthesis and properties of 3-cyano-4-(4-cyanophenyl)-1,4-dihydropyridine-2(3H)-thiones. - Chem. Heterocycl. Comp.,   (Engl.Ed.), 2000, vol.36, N 6, pp. 693-697.
• A.Sobolev, M.C.R.Franssen, N.Makarova, G.Duburs, Aede de Groot. Candida antarctica lipase-catalyzed hydrolysis of 4-substituted bis(ethoxycarbonylmethyl) 1,4-dihydropyridine-3,5-dicarboxylates as the key step in the synthesis of optically active dihydropyridines. - Tetrahedron: Asymmetry, 2000, vol.11, N 22, pp. 4559-4569.
• A.Urtti, Z.Hyvönen, A.Plotniece, N.Makarova, I.Reine, G.Tirzitis, B.Vigante, B. Cekavicus, A.Krauze, R.Zhalubovskis, G.Duburs, M.Turunen, S. Ylä-Herttuala, I.Jääskelainen, M.-R.Toppinen. Cationic amphiphilic 1,4-dihydropyridine derivatives useful for delivery of nucleotide containing compounds.  - Internat. Patent WO 01/62946 A1 (30.08.2001)
• B.Cekavicus, E.Liepinsh, B.Vigante, A.Sobolevs, J.Ozols, G.Duburs.   Unusual cyclization of 1-thianaphthenone-3-dioxide-1,1 to a 1,5-diazabicyclo[3.3.1.]nonane - a heterocyclic analogue of a Troger's base. - Tetrahedron Lett., 2001, vol. 42, N 25, pp. 4239-4241.
• A.Sobolev, M.C.R. Franssen, B.Vigante, B.Cekavicus, R.Zhalubovskis,H.Kooijman, A.L.Spek, G.Duburs, Ae. de Groot. The effect of acyl chain lenght and branching on the enantiosel;ectivity of Candida rugosa lipase in the kinetic resolution of 4-(2-difluoromethoxyphenyl) substituted 1,4-dihydropyridine 3,5-diesters. -   J.Org.Chem., 2002, vol. 67, pp 401-410.
• A.Klegeris, E.Liutkevicius,G.Mikalauskiene,G.Duburs, P.L.McGreer, V.Klusa. Anti-inflammatory effects of cerebrocrast in a model of rat paw edema and on mononuclear THP-1 cells. - Eur. J. Pharmacol., 2002, vol. 441, pp. 203-208.
• J.Briede, K.Heidemanis, I.Dabina, G.Duburs. Effect of cerebrocrast on the function of human platelets and release of the arachidonic acid from plasma membrane. - Cell. Biochem. Funct., 2002, vol. 20, pp. 177-181.
• M.A.S.Fernandes, M.S.Santos, J.A.F.Vicente, A.J.M. Moreno,A.Velena, G.Duburs, C.R.Oliveira. Effects of 1,4-dihydropyridine derivatives (cerebrocrast, gamma-pyrone, glutapyrone,and diethone) on mitochondrial bioenergetics and oxidative stress: a comparative study. - Mitochondrion, 2003, vol.3, pp. 47-59.
• A.Krauze, L.Sile, G.Duburs. Convenient one-pot synthesis of 2-carbamoyl- methylthio-3-cyano- 4,6-diaryl- 5-ethoxycarbonyl-1,4-dihydropyridines. - Heterocyclic Commun., 2003, accepted.  
• M.A.S.Fernandes, M.S.Santos, A.J.M. Moreno, G.Duburs, C.R.Oliveira, J.A.F.Vicente.  Glibenclamide interferes with mitochondrial bioenergetics by inducing changes on membrane ion permeability. - J. Biochem. Mol. Toxicol., 2004, vol. 18, N 3, pp. 162-169.
• E.Bisenieks, J.Uldrikis, G.Duburs. Reaction of 3,5-carbonyl-substituted 1,4-dihydropyriodines with hydrazine hydrate. - Chem. Heterocycl. Comp.,   2004,  N 7, pp. 1014-1021.
• E.Bisenieks, J.Uldrikis, G.Duburs. 3,5-Dicyano-1,4-dihydropyridines as a source for preparation of pyrazole and pyrazolo[3,4-b]pyridine derivatives. - Heterocycl. Commun.   2005,  vol.11(Nr.1), pp. 9-12.
• A.Krauze, R.Vitolina, V.Garaliene, L.Sile, V.Klusa, G.Duburs. 5-(1-Pyridinio)-4,5-trans-1,4,5,6-tetrahydropyridine-2-thiolates - new group of potential cardiotonic drugs. - Eur. J. Med. Chem.   2005,  vol.40(No.11), pp. 1163-1167.
• M.A.S.Fernandes, A.S.Jurado, R.A.Videira, M.S.Santos, A.J.M.Moreno, A.Velena, G.Duburs, C.R.Oliveira, J.A.F.Vicente. Cerebrocrast promotes the contransport of H+ and Cl- in rat liver mitochondria. - Mitochondrion.   2005,  Vol.5, pp.341-351.
• A.Krauze, I.Sturms, J.Popelis, L.Sile, G.Duburs. Synthesis and properties of methyl 4,6-diaryl-2(3H)-thioxo-1,4-dihydropyridine-3-carboxylates. - Heterocycl. Commun.   2005,  Vol.11(Nr.1), pp. 37-42.
• N.I.Ryabokon, R.I.Goncharova, G.J.Duburs, J.Rzeszowska-Wolny. A 1,4-dihydropyridine derivative reduces DNA damage and stimulates DNA repair in human cells in vitro. - Mutation Res.   2005, Vol.587, pp. 52-58.
• J.A.F. Vicente, G.Duburs, V.Klusa, J.Briede, et al. Cerebrocrast as neuroprotective, anti-diabetic and mitochondrial bioenergetic effector: a putative mechanism of action. - Mitochondr. Pharmacol. & Toxicol.(8),  Transworld Research Network, Kerala, India, 2006, pp. 185-197.
• Klimaviciusa L., Klusa V., Duburs G., Kaasic A., Kalda A., Zharkovsky A. Distinct effects of atypical 1,4-dihydropyridines on 1-methyl-4-phenylpyridinium-induced toxicity. - Cell Biochem. Funct., 2007, 25, 15-21.
• Briede J., Duburs G. Protective effect of cerebrocrast on rat brain ischaemia induced by occlusion of both common carotid arteries. - Cell Biochem. Funct., 2007, 25, 203-210.

Research Projects:

• G.Duburs (Head of Project). Transformations and Intramolecular Cyclizations of Hydrated Azines for Synthesis of Polycyclic Systems. Latvian Council of Science (1997-2000).
• G.Duburs (Head of Project). Synthesis and Studies of Novel Potential Drugs, Derivatives of Hydrated Azines. Latvian Council of Science (1997-2000).
• G.Duburs (Associated Contractor), J.Van der Eycken (Coordinator , Gent). ERB-CIPA-CT94-0121: Investigation and Elaboration of Novel Chiral Drugs Prepared by Biotechnological Procedures. EC ( 1995-1998). Programme for Cooperation in Science and Technology with Central and Eastern Europe.
• G.Duburs (Head of Project). Synthesis of Novel Derivatives of Nitrogen Heterocycles - Neuroprotectors and Their Primary Investigation. Latvian Council of Science (2001 -2004).
• G.Duburs (Head of Subproject). Elaboration of Novel Methods of Organic Synthesis for the Preparation of Biologically Active Compounds. Synthesis of Pyridine Derivatives for Eventual Treatment of Neurodegenerative Processes (2002-2005).

Last update 29.02.2008