Ljilja Torović

Synthesis and biological evaluation of new pyrazole- and tetrazole-related C-nucleosides with modified sugar moieties

Abstract 3(5)-Carboxamido-4-(β- d -ribofuranosyl)pyrazoles bearing 2′-benzamido ( 15 ) and 3′-mesyloxy ( 29 ) isosteric groups, as well as the tetrazole C -nucleosides with 2-benzamido-2-deoxy-β- d -ribofuranose ( 19 ) and 3-azido-3-deoxy-β- d -xylofuranose ( 36 ) as sugar segments, have been synthesized starting from d -glucose, by utilizing the 2,5-anhydro- d -glucose ethylene acetal derivatives 1 and 20 as divergent intermediates. The C -nucleosides 15 and 36 were shown to be moderate inhibitors of the in vitro growth of both N2a and BHK 21 tumour cell lines, whereas 29 showed a selective, although not potent cytotoxic activity against N2a cells. Compound 29 also showed a moderate in vitro antiviral activity towards the rabies virus.

De Novo Synthesis of Two New Cytotoxic Tiazofurin Analogues with Modified Sugar Moieties

A divergent synthesis of two novel tiazofurin analogues, 2-(3-deoxy-3-fluoro-beta-D-xylofuranosyl)thiazole-4-carboxamide (2) and 2-(3-acetamido-3-deoxy-beta-D-xylofuranosyl)thiazole-4-carboxamide (3), has been achieved starting from D-glucose. Both nucleoside analogues were evaluated for their in vitro cytotoxicity against several human leukaemia and solid tumour cell lines.

Stereospecific synthesis of two novel cytotoxic pyrazole C-nucleosides from d-glucose

Abstract A multistep stereospecific synthesis of two novel pyrazole C -nucleosides 12 and 21 has been achieved starting from d -glucose, by utilizing the 2,5-anhydro- d -glucose ethylene acetal derivative 1 as a divergent intermediate. The C -nucleoside 12 was shown to be a moderate inhibitor of the in vitro growth of N2a and BHK 21 tumor cell lines, whereas 21 showed a moderate cytotoxic activity only against N2a cells.

Varietal phenolic composition of Probus, Rumenika and Frankovka red wines from Fruška Gora (Serbia) and changes in main compounds during maceration

Red wine is a rich source of different phenolic compounds which contribute to sensorial characteristics and can exhibit various biological properties. The amount of phenolics in wine depends on various factors such as grape variety, environmental conditions and production technology. The extraction of individual polyphenolic compounds during maceration was investigated in this paper. Preliminary determination of specific phenolic compositions in wines produced from grape varieties characteristic for Fruška Gora region (Probus, Frankovka and Rumenika) was also performed. A general trend in extraction of some compounds as well as specific characteristics for each variety regarding phenolic composition was observed. Obtained results showed that among wines of different varieties and vintages, statistically significant differences existed in the content of most analysed phenolics. Wines made from Probus variety were characterised by very high anthocyanin content and Frankovka wines by high content of syringic acid while high contents of piceid (resveratrol), catechin and gallic acid were specific for Rumenika variety. Obtained results have shown that Probus variety has especially great winemaking potential considering high content of phenolic compounds (especially anthocyanins), as well as intensive and stable colour.

Ochratoxin A and aflatoxin B1 in breakfast cereals marketed in Serbia – occurrence and health risk characterisation

ABSTRACT The present paper reports data on the occurrence of ochratoxin A (OTA) and aflatoxin B1 (AFB1) in breakfast cereals marketed in Serbia and interprets consequent dietary exposure. A total of 136 samples was collected in 2012 and 2015 and analysed using high-performance liquid chromatography with fluorescence detection. OTA was detected in 20.7% of the samples in 2012 and 13.0% in 2015, with 3.6% and 0% of the samples above the EU maximum level, respectively. AFB1 was found in low concentrations in 11.1% of the samples collected in 2015, mainly corn based. Comparison of estimated exposure of Serbian adult population with respective toxicological reference values showed no concern for public health.

Aflatoxins and ochratoxin A in flour: a survey of the Serbian retail market

ABSTRACT This report presents data on the occurrence of aflatoxins (AF) and ochratoxin A in different types of flour marketed in Serbia. A total of 114 samples of wheat, buckwheat, rye, oat, barley, rice, millet and corn flour were collected in the period 2012–2016 and analysed using high performance liquid chromatography with fluorescence detection. Among flours other than corn, AFB1 was quantified only in rice, while ochratoxin A (OTA) was found in 29% of the samples. In corn flours the percentage of positive samples varied greatly over the years: AFB1 7.1–80.0%, OTA 30.0–40.6%, with a co-occurrence of 7.1–34.4%. Overall 5.2% of flours other than corn and 10.7% of corn flours exceeded the maximum levels (MLs) for AFB1 and/or OTA. The highest recorded levels were 8.80 μg kg−1 of AFB1 (corn) and 23.04 μg kg−1 of OTA (rye). Overall mean contamination levels of corn flours were 0.53 μg kg−1 of AFB1 and 0.46 μg kg−1 of OTA.

Risk assessment of patulin intake through apple-based food by infants and preschool children in Serbia

ABSTRACT This study reports for the first time in Serbia the occurrence of patulin in apple-based food and the risk assessment associated with patulin intake by infants and preschool children. In total, 214 samples of infant fruit juices (48), infant purée (66), and juices for children (small package with straw, 100) were collected over 3 years (2013–15) and analysed using HPLC with ultraviolet detection. Patulin was found in 43.8% of infant juices and 16.7% of infant purée, with all values below the legal limit of 10 μg kg−1 (maximum 8.3 and 7.7 μg kg−1, respectively). The proportion of contaminated samples among fruit juices for children was 43.0%, with the highest patulin concentration at 30.2 μg kg−1, not exceeding the maximum allowed level of 50 μg kg−1. Risk assessment of patulin intake by Serbian infants and preschool children, conducted by deterministic and probabilistic approaches, revealed a hazard quotient well below 1, indicating a tolerable exposure level and no health concern.

Modulation of Free Amino Acid Profile in Healthy Humans Administered with Mastiha Terpenes. An Open-Label Trial

We aimed to explore whether plasma-free amino acids are modified in response to terpenes administration in healthy humans. In this open-label, single-arm acute trial, seventeen healthy male volunteers were administered with a naturally occurring product of known terpenes—namely mastiha—after overnight fasting. Blood samples were collected at different time points before and after ingestion. We aimed at identifying and quantifying 60 free amino acids in plasma applying Gas Chromatography-Mass Spectrometry. A total of 24 free amino acids were quantified. Branched-chain valine significantly decreased 4 h post-ingestion, whereas proline decreased at 6 h and ornithine at 2 h, compared to 0 h. These novel findings demonstrate that free amino acids levels are modulated in response to terpenes intake in healthy subjects.

Patulin in fruit juices: occurrence, bioaccessibility and risk assessment for the Serbian population

ABSTRACT This paper reports the first study of patulin occurrence in fruit juices and risk assessment related to patulin intake by children, adolescents and adults in Serbia. During 3 consecutive years (2013–2015), 142 fruit (apple or multi-fruit) juices were collected from the market and analysed using HPLC-UV. Patulin was found in 51.4% of juices with 0.7% of the samples in excess of the legal limit of 50 μg kg−1 (mean 4.3 μg kg−1). Apple juices showed significantly higher percentage of contaminated samples (74.0% vs 27.5%), as well as higher mean patulin content (6.4 vs 2.1 μg kg−1) when compared with the multi-fruit ones. Bioaccessibility of patulin in fruit juices was studied using the standardised in vitro digestion method. A mean of 21.6% of the initial patulin amount reached the end of the intestinal phase showing a significant reduction of this toxin during the human digestion process. Risk assessment of patulin intake by Serbian children, adolescents and adults, conducted by deterministic and probabilistic approaches and including the bioaccessibility results, revealed no health concern. Although patulin alone does not represent risk, further research should consider its co-occurrence with other toxic substances in food and potential adverse effects of their mixtures.

Fusarium toxins in corn food products: a survey of the Serbian retail market

ABSTRACT This paper presents data on the occurrence of Fusarium toxins – zearalenone (ZEA), deoxynivalenol (DON) and fumonisins (FUMs) B1 and B2 – in corn flours and corn flakes marketed in Serbia. A total of 71 samples were collected over 2013–2016 and analysed using HPLC with UV or fluorescence detection. In the case of corn flours, none of the samples taken in 2013 exhibited the presence of ZEA or DON, whereas 90% were positive for FUMs. In 2015, occurrence was very high: ZEA 93%, DON 86% and FUMs 100% (mean 43.3, 322.6 and 323.0 μg kg−1, respectively), with 21% of the samples exceeding the maximum level for ZEA and 7% for DON and FUMs. In 2016, a lower occurrence was recorded in the case of ZEA (75%) and DON (38%), with drastically lower mean contamination levels (six- and 10-fold, respectively), while FUMs stayed at 97%, with twofold lower mean. The maximum level was exceeded only for ZEA (3%). The frequency of ZEA–DON–FB1 co-occurrence was 86% in 2015 and 25% in 2016. Regarding corn flakes, occurrence summarised for the study period was 87% ZEA, 73% FUMs and 40% DON. One sample (7%) exceeded the maximum levels for both ZEA and DON. Observed occurrence changes were in agreement with the climatic conditions during corn growing seasons preceding the market release of the processed products.