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Gunars Duburs   Professor  Other 
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Gunars Duburs published an article in November 2018.
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Neven Zarkovic

122 shared publications

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

Marina Petrova

73 shared publications

Department of Medicinal Chemistry; Latvian Institute of Organic Synthesis; Aizkraukles 21 LV-1006 Riga Latvia

Aiva Plotniece

37 shared publications

Latvian Institute of Organic Synthesis, Riga, Latvia

Brigita Vīgante

28 shared publications

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

Anatoly Mishnev

26 shared publications

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

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Distribution of Articles published per year 
(1993 - 2018)
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33
 
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CONFERENCE-ARTICLE 17 Reads 0 Citations Pleiotropic focused anticancer approach by dihydropyridines, dihydropyrimidines and heteroaromatic compounds Gunars Duburs, Brigita Vigante, Egils Bisenieks, Aivars Krau... Published: 14 November 2018
Proceedings of 4th International Electronic Conference on Medicinal Chemistry, doi: 10.3390/ecmc-4-05778
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Complex, focused anticancer therapy approach has been developed in the Latvian Institute of Organic Synthesis by making use of privileged partially hydrogenated nitrogen-containing heterocycles, namely dihydropyridines, dihydropyrimidines, their oxidized heteroaromatic derivatives. Topics of research include:

1. Conventional approach by chemotherapy and synergism of anticancer drugs [1];

2. Inhibition of multidrug resistance by inhibition of drug efflux pumps [2];

3. Mitigation of cancer risk factors – e.g., hepatitis B virus chemotherapy for prevention of chronic liver diseases, because chronic hepatitis, in up to 40% of cases, progresses to cyrrhosis and further to hepatocellular carcinoma [3];

4. Improvement of efficacy of cancer radiotherapy by use of radioprotectors to prevent damage of normal tissues. So, radioprotector diethone (dietone) for skin protection was discovered, elaborated, and developed as ointment. Compounds for protection of eyes, mucous tissues, salivary glands etc have been synthesized. Toxicity of dietone and novel radioprotectors is very low;

5.Amphiphilic compounds have been synthesized, nanoparticles for anticancer drug and gene delivery have been created, pleiotropic properties have been checked, inclusion of magnetic particles for targeted transport performed [4].

Acknowledgements

The research was partially supported by the Latvian State Program Biomedicine.

References

1.Bisenieks E., Duburs G. et al., Pharmaceutical combination of 5-fluorouracil and derivatives of 1,4-dihydropyridine. US 8492413B2, 2013.

2.Krauze A., Grinberga S. et al., Thieno[2,3-b]pyridines – a new class of multidrug resistance (MDR) modulators. Bioorg.Med.Chem. 2014, 22 (21), 5860-5870.

3.Sipola A., Dubova U., et al., Synthesis and evaluation of 1,4-dihydropyrimidine derivatives – hepatitis B virus capsid self-assembly inhibitors. EFMC International Symposium on Medicinal Chemistry. Ljubljana, Slovenia, 2018, P176.

4.Pajuste K. et al., Gene delivery agents possessing antiradical activity: Self-assembling cationic amphiphilic 1,4-dihydropyridine derivatives. New J.Chem. 2013, 37 (10), 3062-3075.

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-carboxylic ac... Anatoly Mishnev, Egils Bisenieks, Ilona Mandrika, Ramona Pet... Published: 12 October 2018
Acta Crystallographica Section E Crystallographic Communications, doi: 10.1107/s2056989018014251
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In the title compound, C25H25NO5S, 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 C(6) chains along the a-axis direction via N—H...O hydrogen bonds. The thienyl fragment is disordered over two sets of sites in a 0.7220 (19):0.2780 (19) ratio.
Article 1 Read 1 Citation 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
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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
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Article 0 Reads 0 Citations 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
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CONFERENCE-ARTICLE 10 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
3rd International Electronic Conference on Medicinal Chemistry, doi: 10.3390/ecmc-3-04679
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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

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