Jelena Stankovic

Target fishing and docking studies of the novel derivatives of aryl-aminopyridines with potential anticancer activity

A set of 16 previously synthesized aryl-aminopyridine and aryl-aminoquinoline derivatives have been evaluated for cytotoxic activity against three cancer cell lines (human cervical cancer-HeLa; human chronic myeloid leukemia-K562; human melanoma-Fem-x) and two types of normal peripheral blood mononuclear cells, with and without phytohemaglutinin (PBMC-PHA; PBMC+PHA). Twelve of the studied compounds showed moderate cytotoxicity, with selectivity against K562 but not the remaining two cancer cell lines. Four compounds were not active in cytotoxicity assays, presumably due to high predicted lipophilicity and low solubility. To rationalize the observed cytotoxic effects, structure-based virtual screening was carried out against a pool of potential targets constructed using the inverse docking program Tarfisdock and bibliographical references. The putative targets were identified on the basis of the best correlation between docking scores and in vitro cytotoxicity. It is proposed that the mechanism of action of the studied aminopyridines involves the disruption of signaling pathways and cancer cell cycle through the inhibition of cyclin-dependent kinases and several tyrosine kinases, namely Bcr-Abl kinase and KIT receptor kinase. The obtained results can guide further structural modifications of the studied compounds aimed at developing selective agents targeting proteins involved in cancer cell survival and proliferation.

Radiation exposure to nuclear medicine staff involved in PET/CT practice in Serbia

The purpose of this work is to evaluate the radiation exposure to nuclear medicine (NM) staff in the two positron emission tomography-computed tomography centres in Serbia and to investigate the possibilities for dose reduction. Dose levels in terms of Hp(10) for whole body and Hp(0.07) for hands of NM staff were assessed using thermoluminescence and electronic personal dosemeters. The assessed doses per procedure in terms of Hp(10) were 4.2-7 and 5-6 μSv, in two centres, respectively, whereas the extremity doses in terms of Hp(0.07) in one of the centres was 34-126 μSv procedure(-1). The whole-body doses per unit activity were 17-19 and 21-26 μSv GBq(-1) in two centres, respectively, and the normalised finger dose in one centre was 170-680 μSv GBq(-1). The maximal estimated annual whole-body doses in two centres were 3.4 and 2.0 mSv, while the corresponding extremity dose in the later one was 45 mSv. Improvements as introduction of automatic dispensing system and injection and optimisation of working practice resulted in dose reduction ranging from 12 up to 67 %.

Cinnamic Acid Derivatives Induce Cell Cycle Arrest in Carcinoma Cell Lines

Cinnamic acid derivatives can be found in plant material, and they possess a remarkable variety of biological effects. In the present study, we have investigated the cytotoxic effects of representative cinnamic acid esters and amides. The cytotoxicity was determined by MTT test on human cervix adenocarcinoma (HeLa), myelogenous leukemia (K562), malignant melanoma (Fem-x), and estrogen-receptor-positive breast cancer (MCF-7) cells, versus peripheral blood mononuclear cells (PBMCs) without or with the addition of the plant lectin phytohemaglutinin (PHA). The compounds tested showed significant cytotoxicity (IC50s between 42 and 166 µM) and furthermore selectivity of these cytotoxic effects on the malignant cell lines versus the PBMCs was also seen, especially when electron-withdrawing groups, such as a cyano group (compound 5), were present on the aromatic rings of the alcohol or amine parts of the cinnamic acid derivatives. The additional study on cell cycle phase distribution indicated that novel cinnamic acid derivatives inhibit cell growth by induction of cell death. Thus, cinnamic acids derivatives represent important lead compounds for further development of antineoplastic agents.

Synthesis, characterization, and in vitro antiproliferative and antibacterial studies of tetraazamacrocyclic complexes of Co(II) and Cu(II) with pyromellitic acid

Abstrcat New cationic tetranuclear Co(II) and neutral binuclear Cu(II) complexes with tpmc (N,N′,N″,N″′-tetrakis-(2-pyridylmethyl)-1,4,8,11-tetraazacyclotetradecane) and bridging pyromellitate ligand pma (tetraanion 1,2,4,5-benzenetetracarboxylic acid) were isolated. The composition of the compounds is proposed based on elemental analyses (C, H, N, M=Cu, Co), molar conductivity determination, UV-Vis, FTIR, EPR, LC-MS and reflectance spectroscopy, magnetic measurements, cyclic voltammetry, as well as TG and DTA. It is proposed that in [Co4(pma)(tpmc)2](ClO4)4·6H2O (1), cobalt(II) is six-coordinate out of cyclam rings and one OCO− from pma participates in coordination with one Co(II). In the case of [Cu2(pma)tpmc]∙8H2O (2), one OCO− from pma bridges two Cu(II). The cytotoxic activity of 1 and 2 was tested against tumor cell lines human cervix adenocarcinoma (HeLa), estrogen-receptor-positive human breast cancer (MCF-7), human myelogenous leukemia (K562), and the human Caucasian Burkitt’s lymphoma (Ramos). The IC50 values for 1 and 2 were within the range 44.66 ± 2.39 to 152.40 ± 2.28 μM, and from 140.88 ± 3.51 to 192.05 ± 2.09 μM, respectively. Both 1 and 2 were tested for antimicrobial activity. We determined that minimal inhibitory concentration for 1 against Staphylococcus aureus, Bacillus subtilis, and Klebsiella pneumoniae was 25 mM. Complex 2 did not express activity against tested microbial strains.

Occupational dose assessment in interventional cardiology in Serbia

The objective of this work is to assess the occupational dose in interventional cardiology in a large hospital in Belgrade, Serbia. A double-dosimetry method was applied for the estimation of whole-body dose, using thermoluminescent dosemeters, calibrated in terms of the personal dose equivalent Hp(10). Besides the double-dosimetry method, eye dose was also estimated by means of measuring ambient dose equivalent, H*(10), and doses per procedure were reported. Doses were assessed for 13 physicians, 6 nurses and 10 radiographers, for 2 consequent years. The maximum annual effective dose assessed was 4.3, 2.1 and 1.3 mSv for physicians, nurses and radiographers, respectively. The maximum doses recorded by the dosemeter worn at the collar level (over the apron) were 16.8, 11.9 and 4.5 mSv, respectively. This value was used for the eye lens dose assessment. Estimated doses are in accordance with or higher than annual dose limits for the occupational exposure.

HAND DOSE EVALUATION OF OCCUPATIONALLY EXPOSED STAFF IN NUCLEAR MEDICINE.

Manipulation of unsealed radiation sources in nuclear medicine (NM) departments involves non-uniform exposure to staff and high skin doses to the upper extremities from direct and scattered radiations. Conducted studies have shown that the annual dose limits could be exceeded and the continuous dose monitoring of NM workers hands is needed. The aim of this article is to show results of hand dose monitoring in terms of operational quantity Hp(0.07) for occupationally exposed NM workers to beta and gamma radiations in the largest NM centre in Serbia. Dose assessment was done by means of thermoluminescent ring dosemeters DXT-RAD (LiF:Mg,Ti). Monthly and annual doses were evaluated for a 5-y period (2010-14). Monitored NM staff was categorised according to the type of work, as nurses, radiographers, laboratory technicians and radiochemists. Performed evaluation showed that annual hand doses were within the annual limit for all staff categories, but further optimisation of working practice is needed.

Toward utilization of MCNP5 particle track output file for simulation problems in photon spectrometry

Abstract Pulse height distribution (PHD) registered by a spectrometer is influenced by various physical phenomena such as photon interactions as well as disturbance produced by the electronic circuits inside the spectrometer. Therefore, spectrometry measurements of gamma and X-ray radiation inaccurately represent primary spectra. In order to overcome spectrum disruption, spectrum unfolding has to be applied. One of the common tools used in the unfolding process is Monte Carlo simulation of spectrometer response to monochromatic photons. The purpose of this work is to develop a new method for simulating CdTe semiconductor spectrometer response to monochromatic photons that can be further used for the spectrum unfolding procedure. The method is based upon post-processing of the particle track (PTRAC) output file generated by the MCNP5 program. In addition to the spectrometry output, this method provides information for each specific photon interaction inside the spectrometer active volume, which is required when taking into account spectrometer charge collection. The PTRAC generated detector response and the measured spectrum were in good agreement. The results obtained showed that this method can be used to generate precise response functions of gamma and X-ray spectrometers.