Please login first
Gunars Duburs   Professor  Other 
Timeline See timeline
Gunars Duburs published an article in October 2018.
Research Keywords & Expertise
0 A
0 ATP
0 Blood Pressure
0 Cytokines
0 0
Top co-authors See all
Neven Zarkovic

110 shared publications

Laboratory for Oxidative Stress, Rudjer Boskovic Institute, 10000 Zagreb, Croatia

Marina Petrova

94 shared publications

Latvian Institute of Organic Synthesis

Aiva Plotniece

31 shared publications

Latvian Institute of Organic Synthesis, Aizkraukles Str. 21, Riga LV-1006, Latvia

Lidija Milkovic

22 shared publications

Laboratory for Oxidative Stress (LabOS), Ruđer Bošković Institute, Division of Molecular Medicine, 10 000 Zagreb, Croatia;(L.M.);(A.Č.G.)

Anatoly Mishnev

21 shared publications

Latvian Institute of Organic Synthesis, Aizkraukles str. 21, Riga, LV-1006, Latvia

52
Publications
40
Reads
5
Downloads
116
Citations
Publication Record
Distribution of Articles published per year 
(1997 - 2018)
Total number of journals
published in
 
33
 
Publications See all
Article 0 Reads 0 Citations Crystal structure and metabolic activity of 4-(thien-2-yl)-2-methyl-5-oxo-1,4,5,6,7,8-hexa­hydro­quinoline-3-carb­oxy­li... Anatoly Mishnev, Egils Bisenieks, Ilona Mandrika, Ramona Pet... Published: 12 October 2018
Acta Crystallographica Section E Crystallographic Communications, doi: 10.1107/S2056989018014251
DOI See at publisher website PubMed View at PubMed ABS Show/hide abstract
In this condensed 1,4-di­hydro­pyridine derivative, which exhibits metabolism-regulating activity, the 1,4-di­hydro­pyridine ring adopts a flattened boat conformation while the cyclo­hexenone ring is in an envelope conformation. Mol­ecules in the crystal are assembled into chains along the a-axis direction via N—H⋯O hydrogen bonds.
Article 2 Reads 2 Citations Antioxidative 1,4-Dihydropyridine Derivatives Modulate Oxidative Stress and Growth of Human Osteoblast-Like Cells In Vit... Lidija Milkovic, Tea Vukovic, Neven Zarkovic, Franz Tatzber,... Published: 19 September 2018
Antioxidants, doi: 10.3390/antiox7090123
DOI See at publisher website PubMed View at PubMed ABS Show/hide abstract
Oxidative stress has been implicated in pathophysiology of different human stress- and age-associated disorders, including osteoporosis for which antioxidants could be considered as therapeutic remedies as was suggested recently. The 1,4-dihydropyridine (DHP) derivatives are known for their pleiotropic activity, with some also acting as antioxidants. To find compounds with potential antioxidative activity, a group of 27 structurally diverse DHPs, as well as one pyridine compound, were studied. A group of 11 DHPs with 10-fold higher antioxidative potential than of uric acid, were further tested in cell model of human osteoblast-like cells. Short-term combined effects of DHPs and 50 µM H2O2 (1-h each), revealed better antioxidative potential of DHPs if administered before a stressor. Indirect 24-h effect of DHPs was evaluated in cells further exposed to mild oxidative stress conditions induced either by H2O2 or tert-butyl hydroperoxide (both 50 µM). Cell growth (viability and proliferation), generation of ROS and intracellular glutathione concentration were evaluated. The promotion of cell growth was highly dependent on the concentrations of DHPs used, type of stressor applied and treatment set-up. Thiocarbatone III-1, E2-134-1 III-4, Carbatone II-1, AV-153 IV-1, and Diethone I could be considered as therapeutic agents for osteoporosis although further research is needed to elucidate their bioactivity mechanisms, in particular in respect to signaling pathways involving 4-hydroxynoneal and related second messengers of free radicals.
Article 0 Reads 0 Citations Searching for inhibitors of human H 2 S-synthesizing enzymes by orthogonal methods Karim Zuhra, Pedro M.F. Sousa, Giulia Paulini, Ana Rita Lemo... Published: 01 May 2018
Free Radical Biology and Medicine, doi: 10.1016/j.freeradbiomed.2018.04.509
DOI See at publisher website
Article 0 Reads 1 Citation Study of interactions of mononucleotides with 1,4-dihydropyridine vesicles using NMR and ITC techniques Ruslan Muhamadejev, Marina Petrova, Rufus Smits, Aiva Plotni... Published: 01 January 2018
New Journal of Chemistry, doi: 10.1039/c8nj00160j
DOI See at publisher website
CONFERENCE-ARTICLE 16 Reads 0 Citations <strong>Design and Synthesis of Small-molecule Hepatitis B Virus Capsid Self-assembly Inhibitors</strong> Anda Sīpola, Unda Dubova, Brigita Vīgante, Karīna Spunde, Ta... Published: 01 November 2017
Proceedings of 3rd International Electronic Conference on Medicinal Chemistry, doi: 10.3390/ecmc-3-04679
DOI See at publisher website ABS Show/hide abstract

An estimated 240 million persons worldwide are chronically infected with hepatitis B virus (HBV). Chronic hepatitis B (CHB) in up to 40% of cases progresses to liver cirrhosis, hepatic decompensation, and hepatocellular carcinoma, a leading cause of cancer-related morbidity and mortality worldwide [1]. We are focused on original antiviral strategy intended to suppress the self-assembly process of HBV core (HBc) protein as one of the promising ways to cure CHB without induction of drug resistance. Targeting the capsid protein of HBV and thus interrupting normal capsid formation have been an attractive approach to block the replication of HBV.

Heteroaryldihydropyrimidines (HAPs) were shown to bind the HBV core proteins and misdirect the assembly of the capsid in vitro. We carried out structural optimizations based on HAPs analogue Bay 41-4109 and structure-activity relationship studies [2].

Newly synthesized HAPs 1 and 2 were evaluated for their ability to disrupt the capsid assembly in cell culture, and promising candidates were selected for further evaluation of antiviral activity and discovery of mechanisms of compound action.

 

Acknowledgments: The author gratefully acknowledges Gunārs and Renāte Duburi for provided scholarship.

References:

[1] World Health Organization (2016) WHO Hepatitis B Fact Sheet (World Health Organization, Geneva)

[2] Qiu, Z. et.al. (2016), Design and Synthesis of Orally Bioavailable 4-Methyl Heteroaryldihydropyrimidine Based Hepatitis B Virus (HBV) Capsid Inhibitors. J. Med. Chem. 59, 7651-7666

Article 0 Reads 2 Citations Modifications of expression of genes and proteins involved in DNA repair and nitric oxide metabolism by carbatonides [di... Kristīne Ošiņa, Elina Leonova, Sergejs Isajevs, Larisa Bauma... Published: 26 September 2017
Archives of Industrial Hygiene and Toxicology, doi: 10.1515/aiht-2017-68-2945
DOI See at publisher website ABS Show/hide abstract
Studies on the pathogenesis of diabetes mellitus complications indicate that the compounds reducing free radicals and enhancing DNA repair could be prospective as possible remedies. Carbatonides, the disodium-2,6-dimethyl-1,4- dihydropyridine-3,5-bis(carbonyloxyacetate) derivatives, were tested for these properties. EPR spectroscopy showed that metcarbatone was an effective scavenger of hydroxyl radicals produced in the Fenton reaction, etcarbatone, and propcarbatone were less effective, styrylcarbatone was ineffective. UV/VIS spectroscopy revealed that styrylcarbatone manifested a hyperchromic effect when interacting with DNA, while all other carbatonides showeda hypochromic effect. Rats with streptozotocin induced type 1 DM were treated with metcarbatone, etcarbatone or styrylcarbatone (all compounds at doses 0.05 mg kg-1 or 0.5 mg kg-1) nine days after the DM approval. Gene expression levels in kidneys and blood were evaluated by quantitative RT-PCR; protein expression - immunohistochemically in kidneys, heart, sciatic nerve, and eyes; DNA breakage - by comet assay in nucleated blood cells. Induction of DM induced DNA breaks; metcarbatone and styrylcarbatone (low dose) alleviated this effect. Metcarbatone and etcarbatone up-regulated mRNA and protein of eNOS in kidneys of diabetic animals; etcarbatone also in myocardium. Etcarbatone reduced the expression of increased iNOS protein in myocardium, nerve, and kidneys. iNos gene expression was up-regulated in kidneys by etcarbatone and metcarbatone in diabetic animals. In blood, development of DM increased iNos gene expression; etcarbatone and metcarbatone normalised it. Etcarbatone up-regulated the expression of H2AX in kidneys of diabetic animals but decreased the production of c-PARP1. Taken together, our data indicate that carbatonides might have a potential as drugs intended to treat DM complications.
Top