Here, we describe the synthesis and biologic activity evaluation of 20 novel synthetic marine sponge alkaloid analogues with 2-amino-1H-imidazol (2-AI) core. Cytotoxicity was tested on murine 4T1 breast cancer, A549 human lung cancer, and HL-60 human myeloid leukemia cells by the resazurin assay. A total of 18 of 20 compounds showed cytotoxic effect on the cancer cell lines with different potential. Viability of healthy human fibroblasts and peripheral blood mononuclear cells upon treatment was less hampered compared to cancer cell lines supporting tumor cell specific cytotoxicity of our compounds. The most cytotoxic compounds resulted the following IC50 values 28: 2.91 mu M on HL-60 cells, and 29: 3.1 mu M on 4T1 cells. The A549 cells were less sensitive to the treatments with IC50 15 mu M for both 28 and 29. Flow cytometry demonstrated the apoptotic effect of the most active seven compounds inducing phosphatidylserine exposure and sub-G1 fragmentation of nuclear DNA. Cell cycle arrest was also observed. Four compounds caused depolarization of the mitochondrial membrane potential as an early event of apoptosis. Two lead compounds inhibited tumor growth in vivo in the 4T1 triple negative breast cancer and A549 human lung adenocarcinoma xenograft models. Novel marine sponge alkaloid analogues are demonstrated as potential anticancer agents for further development.

An elegant P(nBu)(3)-triggered synthetic approach has been developed towards multisubstituted 5,6-dihydropyridin-2(1H)-one and pyridin-2(1H)-one derivatives exploiting a domino process involving retro-Claisen/intra-MBH/Wittig/vinylogous aldol transformations as well as retro-Claisen/intra-MBH/ylide hydrolysis/oxidation sequences. This transformation demonstrates chemo- and regioselectivity as well as accessible high diversity enchancement in 17-90% isolated yield.

The migration of health care workers is a longstanding process which causes shortages in the sending countries. The Eastern enlargements of the European Union strengthened the East-West migration flows causing serious political controversies and jeopardising medical services. Hungary is also heavily affected by these processes and in the last 10 years; thousands of doctors and nurses left the country. Managing migration processes requires complex policy answers with the involvement of actors from various spatial scales - but most of the studies on medical migration from Hungary focuses on the national scale. To fill this research gap, this study aims to analyse local political responses to the outmigration through the content analysis health care development documents to reveal the role of local scale. On local scale individual needs and preferences, emotional factors can influence the decision on staying or moving. Therefore, local policies, which take local features into account and apply place-based approach, can be useful elements of (re)migration policies in the case of health care workers, too.

The shortage and uneven geographic distribution of health workers is considered a severe global problem nowadays. Recent studies examining inequalities in health workforce supply at various spatial scales suggest that health workers' geographic distribution follows a core-periphery pattern as the more developed areas are generally better supplied with health labour than the less developed ones. Here, we explore the regional patterns and temporal changes of the geographic distribution of physicians in the European Union (EU) at the Nomenclature of territorial units for statistics (Nomenclature des unites territoriales statistiques - NUTS) 2 level between 2006 and 2018. We also compare the levels of concentration and inequality in the geographic distribution of physicians, economic development, and health outcomes. We utilise a mix of statistical methods such as descriptive statistics, indices of concentration and inequality, and bivariate correlation analysis based on Eurostat data. Our results provide evidence that the regional distribution of physicians in the EU shows a core-periphery pattern: NUTS regions with capital cities or metropolitan areas have more physicians. In addition, the regional patterns of the distribution of physicians in the EU are stable in time, and their geographic concentration is strengthening in the long run. Our results also suggest that there is a positive relationship between the geographic distribution of physicians and health outcomes;however, this relationship needs further investigation.

An efficient protocol for the preparation of 4,5‐functionalised 2‐amino‐1H‐imidazoles as fragment‐like structures was developed in isolated yields up to 95 %. The demonstrated one‐pot manner includes an intramolecular oxidative annulation and ring cleavage sequence starting from Mannich precursors. The suggested one‐pot sequential synthetic methodology is easy to apply in automatic and robotic chemistry laboratories for which a rapidly increasing demand is foreseen because of the ongoing revolution in the field of continuous manufacturing of pharmaceutical drug substances and products. Further transformation utilities such as Groebke–Blackburn–Bienaymé 3CR and the formation of marine alkaloid analogs were also represented.

An IBX/NIS-induced intramolecular oxidative annulation of Mannich-type substrates is reported. This metal-free approach involving iodination, NH-oxidation, intramolecular C-N bond formation, and retro-Claisen-Schmidt sequence provides the construction of imidazo[1,2-a]pyridine, imidazo[1,2-a]pyrimidine as well as imidazo[1,2-a]pyrazine frameworks with yields up to 93%. In addition, a sequential one-pot process is also presented.

Urbanization trends in Hungary have been similar during the last decades to those of other Central and Eastern European countries. After 40-50 years of mass-urbanization the phase of suburbanization started. We could see out-migration from villages, especially from small ones. Because of this large-scale out-migration the residual population of these villages became older, so we can see that out-migration and natural decrease are parallel nowadays. In some cases the population decline of these small villages became critical; the population of more than 40 villages in Hungary is less than 25, according to the census of 2011. Because of the changing administrative structure, we can see those villages which were independent administrative units by the 1910 Hungarian Census irrespectively of these villages are administrative units (some of the Hungarian small villages) or not (the other part of Hungarian villages) nowadays. The area of investigation is Hungary. We could have a look at the ways and the types of decline by the reason of underpopulation, by clusters of population change and by size of these settlements. Most of the villages had steep decline of population during the last century, but in some of them we could see that the trends are changing. Because of the natural increase and the new functions (eco-village, tourism, suburbanization, counter-urbanization), the population is stable or increasing now. By the clusters of these villages we could create clear types of small villages and their geographic distribution is also understandable.

Social segregation is one of the most important social problems in Central-Eastern Europe not only in urban, but also rural areas. The social segregation usually coexists with ethnic segregation. In Western-Europe we can see segregation mainly in towns, but in Eastern-Europe also in villages, usually connecting with Roma people. In the last decades number of population of small villages dropped dramatically and in some regions the most disadvantaged social groups appeared in these villages. Nowadays some of these villages have geographical, social and ethnic disadvantages together. To stop marginalization of people living in poverty is one of the biggest challenges nowadays in Hungary. According to the definition of Hungarian Statistical Office the whole settlement is regarded segregated if it has less than 200 inhabitants, therefore we also determined this limit. These settlements with population below 200 were the subject of this study. A complex indicator system was established containing six indicators (educational level, unemployment, comfort level of homes, etc.) These indicators served as the base of cluster analysis using the K-means algorithm resulted in five clusters. The 58 segregated settlements can be found mainly in peripheral areas of Northeasternand Southwestern-Hungary. The proportion of Roma population is high in most of the segregated settlements. The aim of the paper is to describe the most important social problems of the smallest Hungarian villages, to find the groups of villages with social segregation and marginalization and to find context between marginalization, social and ethnic segregation amongst the tiny Hungarian villages.