Synthesis, characterizaon and potenal cytotoxity of o,o'-dialkil-(s,s)-ethilenediamine-n,n'- di--2-(4-methyl)-pentanoate and the corresponding palladium(ii), planum(ii) and planum(iv) complexes

This works describes synthesis, characterization and potential cytotoxity of O,O'- -dialkyl-(S,S)-ethylenediamine-N,N'-di-2-(4-methyl)-pentanoic acid, [(S,S)-H4eddl]Cl2, as well as their corresponding palladium(II), platinum(II) and platinum(IV) complexes. Esters (S,S)-R2eddl·2HCl (R = ethyl, n-propyl, n-butyl and n-pentyl) were obtained by instillation of thionyl chloride in an appropriate absolute alcohol, and then refluxing with addition of (S,S)-ethylenediamine-N,N'-di-2-(4-methyl)-pentanoic acid. All of the esters were obtained as dihydrochlorides: (S,S)-Et2eddl·2HCl, (S,S)-Pr2eddl·2HCl, (S,S)-Bu2eddl·2HCl, (S,S)-Pe2eddl·2HCl. Esters were characterized by elemental analysis, IR and NMR spectroscopy, and in the case of (S,S)-Pr2eddl·2HCl the structure was confirmed by X-ray structural analysis

In silico methods in stability testing of hydrocortisone, powder for injections: Multiple regression analysis versus dynamic neural network

This article presents the possibility of using of multiple regression analysis (MRA) and dynamic neural network (DNN) for prediction of stability of Hydrocortisone 100 mg (in a form of hydrocortisone sodium succinate) freeze-dried powder for injection packed into a dual chamber container. Degradation products of hydrocortisone sodium succinate: free hydrocortisone and related substances (impurities A, B, C, D and E; unspecified impurities and total impurities) were followed during stress and formal stability studies. All data obtained during stability studies were used for in silico modeling; multiple regression models and dynamic neural networks as well, in order to compare predicted and observed results. High values of coefficient of determination (0.950.99) were gained using MRA and DNN, so both methods are powerful tools for in silico stability studies, but superiority of DNN over mathematical modeling of degradation was also confirmed

Supplementary data for article: Pantelić, N.; Zmejkovski, B. B.; Kolundžija, B.; Crnogorac, M. Đ.; Vujić, J. M.; Dojčinović, B.; Trifunović, S. R.; Stanojković, T. P.; Sabo, T. J.; Kaluđerović, G. N. In Vitro Antitumor Activity, Metal Uptake and Reactivity with Ascorbic Acid and BSA of Some Gold(III) Complexes with N,N′-Ethylenediamine Bidentate Ester Ligands. Journal of Inorganic Biochemistry 2017, 172, 55–66. https://doi.org/10.1016/j.jinorgbio.2017.04.001

Supplementary material for: [https://doi.org/10.1016/j.jinorgbio.2017.04.001]Related to published version: [http://cherry.chem.bg.ac.rs/handle/123456789/2478]Related to accepted version: [http://cherry.chem.bg.ac.rs/handle/123456789/3070

Synthesis, Characterization, and Cytotoxicity of a Novel Gold(III) Complex with O,O-Diethyl Ester of Ethylenediamine-N,N-Di-2-(4-Methyl)Pentanoic Acid

A novel gold(III) complex, [AuCl2{(S,S)-Et(2)eddl}]PF6, ((S,S)-Et(2)eddl = O,O-diethyl ester of ethylenediamine-N,N-di-2-(4-methyl)pentanoic acid) was synthesized and characterized by IR, 1D (H-1 and C-13), and 2D (H,H-COSY and H,H-NOESY) NMR spectroscopy, mass spectrometry, and elemental analysis. Density functional theory calculations confirmed that (R,R)-N,N diastereoisomer was energetically the most stable isomer. In vitro antitumor action of ligand precursor [(S,S)-H(2)Et(2)eddl]Cl-2 and corresponding gold(III) complex was determined against tumor cell lines: human adenocarcinoma (HeLa), human colon carcinoma (LS174), human breast cancer (MCF7), non-small cell lung carcinoma cell line (A549), and non-cancerous cell line human embryonic lung fibroblast (MRC-5) using microculture tetrazolium test (MTT) assay. The results indicate that both ligand precursor and gold(III) complex have showed very good to moderate cytotoxic activity against all tested malignant cell lines. The highest activity was expressed by [AuCl2{(S,S)-Et(2)eddl}]PF6 against the LS174 cells, with IC50 value of 7.4 +/- 1.2 mu M

Supplementary data for article: Pantelić, N.; Zmejkovski, B. B.; Kolundžija, B.; Crnogorac, M. Đ.; Vujić, J. M.; Dojčinović, B.; Trifunović, S. R.; Stanojković, T. P.; Sabo, T. J.; Kaluđerović, G. N. In Vitro Antitumor Activity, Metal Uptake and Reactivity with Ascorbic Acid and BSA of Some Gold(III) Complexes with N,N′-Ethylenediamine Bidentate Ester Ligands. Journal of Inorganic Biochemistry 2017, 172, 55–66. https://doi.org/10.1016/j.jinorgbio.2017.04.001

Supplementary material for: [https://doi.org/10.1016/j.jinorgbio.2017.04.001]Related to published version: [http://cherry.chem.bg.ac.rs/handle/123456789/2478]Related to accepted version: [http://cherry.chem.bg.ac.rs/handle/123456789/3070

First molecular-cytogenetic characterization of Fanconi anemia fragile sites in primary lymphocytes of FA-D2 patients in different stages of the disease

Background: Fanconi anemia (FA) is a chromosomal instability syndrome characterized by increased frequency of chromosomal breakages, chromosomal radial figures and accelerated telomere shortening. In this work we performed detailed molecular-cytogenetic characterization of breakpoints in primary lymphocytes of FA-D2 patients in different stages of the disease using fluorescent in situ hybridization. Results: We found that chromosomal breakpoints co-localize on the molecular level with common fragile sites, whereas their distribution pattern depends on the severity of the disease. Telomere quantitative fluorescent in situ hybridization revealed that telomere fusions and radial figures, especially radials which involve telomere sequences are the consequence of critically shortened telomeres that increase with the disease progression and could be considered as a predictive parameter during the course of the disease. Sex chromosomes in FA cells are also involved in radial formation indicating that specific X chromosome regions share homology with autosomes and also could serve as repair templates in resolving DNA damage. Conclusions: FA-D2 chromosomal breakpoints co-localize with common fragile sites, but their distribution pattern depends on the disease stage. Telomere fusions and radials figures which involve telomere sequences are the consequence of shortened telomeres, increase with disease progression and could be of predictive value

Effect of plant extracts of Kitaibelia vitifolia on antioxidant activity, chemical characteristics, microbiological status and sensory properties of Pirotski Kachkaval cheese

© 2015, Association of Chemists and Chemical Engineers of Serbia. All rights reserved. The aim of our study was to evaluate the impact of cheese (Pirotski Kachkaval) fortification by polyphenols attributed to Kitaibelia vitifolia ethanol herb extract, applied in two different manners (added to the cheese curd after texturizing or sprayed on surface of cheese). Investigation of the used antioxidant effects of polyphenols, physic-chemical composition, microbiological quality and sensory properties of Pirotski Kachkaval was undertaken. Antioxidant activity of conventional and fortified cheese was evaluated by five contemporary and compatible methods, and revealed a slight emphasis on phenol-linked antioxidant activity of fortified samples of cheese in comparison to samples of the control group. Fortified Pirotski Kachkaval had higher sensory evaluation scores than the controls. Statistically significant (P 0.05)

Stereospecific ligands and their complexes - Part XIV: Crystal structure of O,O’-dipropyl ester of (S,S)-ethylenediamine-N,N’-di-2-(4-methyl)-pentanoic acid dihydrochloride

Bidentate N,N'-ligand precursor, O,O'-dipropyl ester of (S,S)- ethylenediamine-N,N'-di-2-(4-methyl)-pentanoic acid dihydrochloride, [(S,S)- H4eddl]Cl2, was prepared and its crystal structure is given herein. It crystallizes in a P42 space group of tetragonal crystal system with a = 16.5620 (2) Å, b = 16.5620 (2) Å, c = 5.2240 (1) Å and Z = 2

A modified RP-HPLC method for the determination of the pKa values of synthesized β-hydroxy-β-arylalkanoic acids

The pKa values of twelve β-hydroxy-β-arylalkanoic acids and ibuprofen were determined using a modified RP-HPLC method. The stationary phase was octadecyl modified (C-18) silica gel, and the mobile phases were mixtures of methanol and one of ten different buffers (60:40 volume ratio). The mean retention time of each compound was plotted against the pH of each of the ten used mobile phases. The inflection point of the obtained sigmoidal curve represents the s w pKa of a compound. Using s w pKa in previously established equations for the specific methanol/buffer mixture, the w w pKa values (in pure water) were calculated. The obtained w w pKa values for the synthesized compounds were in a range from 3.40 to 3.74, and the w w pKa for ibuprofen was 4.27. The Predicted pKa values for this type of compounds in the MarvinSketch 5.11.5. Program were in poor correlation with the experimental results, while in ACD/ /I-Labs pKa values were calculated as a wide range. [Project of the Serbian Ministry of Education, Science and Technological Development, Grant no. 172041

Prediction of current species distribution of Cheilosia proxima group (Diptera: Syrphidae) on the Balkan peninsula

Predicting species distribution in different climates is most often made by climate models (“climate envelope models” - CEM) which are using the current geographical distribution of species and climate characteristics of the area. Hoverflies (Insecta: Diptera: Syrphidae) can act as bioindicators and monitors of climate change and habitat quality. Cheilosia Meigen, 1822 is one of the largest hoverflies genera, with about 450 described species. The aim of this study was to model the current potential distribution of six species from Cheilosia proxima group on the Balkan Peninsula (Cheilosia aerea Dufour, 1848, C. balkana Vujić, 1994, C. gigantea Zetterstedt, 1838, C. pascuorum Becker, 1894, C. proxima Zetterstedt, 1843 and C. rufimana Becker, 1894) using maximum entropy modeling (Maxent). It is observed that parameters with highest influence on the analyzed species are Altitude and BIO 15 (Precipitation Seasonality) for all species, except C. rufimana. Parameter that also substantially influenced for all species, except C. pascuorum, is BIO 18 (Precipitation of Warmest Quarter). The models of current distribution have shown that the most important area of the Balkan Peninsula, for species from Cheilosia proxima group, is Dinaric mountains. Information obtained in this paper can help in future monitoring of species, as well as for the conservation measures, especially for endemics and rare species. [Projekat Ministarstva nauke Republike Srbije, br. 173002 i br. 43002