122 shared publications
LabOS, Rudjer Boskovic Institute, Laboratory for Oxidative Stress, 10000 Zagreb, Croatia
73 shared publications
Department of Medicinal Chemistry; Latvian Institute of Organic Synthesis; Aizkraukles 21 LV-1006 Riga Latvia
37 shared publications
Latvian Institute of Organic Synthesis, Riga, Latvia
28 shared publications
Latvian Institute of Organic Synthesis, Aizkraukles iela 21, LV-1006 Riga, Latvia
26 shared publications
Latvian Institute of Organic Synthesis, Aizkraukles str. 21, Riga, LV-1006, Latvia
(1993 - 2018)
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 ;
2. Inhibition of multidrug resistance by inhibition of drug efflux pumps ;
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 ;
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 .
The research was partially supported by the Latvian State Program Biomedicine.
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.
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 . 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 .
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.
 World Health Organization (2016) WHO Hepatitis B Fact Sheet (World Health Organization, Geneva)
 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