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6 results on '"Bjelaković, Mira"'

1. Polysaccharide-fullerene supramolecular hybrids: Synthesis, characterization and antioxidant activity

Author

Kop, Tatjana, Jakovljević, Dragica M., Živković, Ljiljana S., Žekić, Andrijana, Beškoski, Vladimir, Milić, Dragana, Gojgić-Cvijović, Gordana D., Bjelaković, Mira, Kop, Tatjana, Jakovljević, Dragica M., Živković, Ljiljana S., Žekić, Andrijana, Beškoski, Vladimir, Milić, Dragana, Gojgić-Cvijović, Gordana D., and Bjelaković, Mira

Abstract

An efficient encapsulation of the fullerene into two hydrophobized and one native polysaccharide provided water soluble supramolecular hybrids. After covalent modification of polysaccharides by cholesterol, noncovalent hybrids were prepared by a three-step procedure, including mixing of individual aqueous solutions of hydrophobized, as well as native sugar with solution of the fullerene in pyridine, dialysis and lyophilization. Although the degree of the fullerene incorporation into hydrophobized substrates, cholesterol-levan and cholesterol-pullulan, was lower in comparison to the native polysaccharide levan, hydrophobization provided nanoparticles with improved properties. The particle size distribution, studied by dynamic light scattering and scanning electron microscopy revealed formation of moderately polydisperse aggregates, with the diameter contraction in comparison to the corresponding free polysaccharide, especially in the case of hydrophobized substrates. The morphological examination, done by scanning electron microscopy indicated the self-organization of the fullerene-native polysaccharide to round individual structures, while fullerene-hydrophobized polysaccharide hybrids tend to form networks. The antioxidant activity of the synthesized polysaccharide-C60 noncovalent hybrids versus starting polysaccharides was investigated by the DPPH radical scavenging and the β-carotene-linoleic acid bleaching methods. In all three complexes, the radical scavenging ability of the fullerene remained preserved, and a positive effect of levan hydrophobization was observed.

Published
2020

2. SR-FTIR spectro-microscopic interaction study of biochemical changes in HeLa cells induced by Levan-C60, Pullulan-C60, and their cholesterol-derivatives

Author

Nešić, Maja D., Dučić, Tanja, Liang, Xinyue, Algarra, Manuel, Mi, Lan, Korićanac, Lela, Žakula, Jelena, Kop, Tatjana, Bjelaković, Mira S., Mitrović, Aleksandra D., Gojgić-Cvijović, Gordana D., Stepić, Milutin, Petković, Marijana, Nešić, Maja D., Dučić, Tanja, Liang, Xinyue, Algarra, Manuel, Mi, Lan, Korićanac, Lela, Žakula, Jelena, Kop, Tatjana, Bjelaković, Mira S., Mitrović, Aleksandra D., Gojgić-Cvijović, Gordana D., Stepić, Milutin, and Petković, Marijana

Abstract

Objects of the present study are improved fullerene C60 drug carrier properties trough encapsulation by microbial polysaccharides, levan (LEV), pullulan (PUL), and their hydrophobized cholesterol-derivatives (CHL and CHP), that show better interaction with cancer cells. The zeta potential, polydispersity index, and the diameter of particles were determined, and their cytotoxicity against three cancer cell lines were tested. Biochemical changes in HeLa cells are analyzed by synchrotron radiation (SR) FTIR spectro-microscopy combined with the principal component analysis (PCA). The most significant changes occur in HeLa cells treated with LEV-C60 and correspond to the changes in the protein region, i.e. Amide Iband, and the changes in the structure of lipid bodies and membrane fluidity are evident. The highest cytotoxicity was also induced by LEV-C60. In HeLa cells, cytotoxicity could not be strictly associated with biochemical changes in lipids, proteins and nucleic acids, but these findings are significant contribution to the study of the mechanism of interaction of C60-based nanoparticles with cellular biomolecules. In conclusion, LEV, PUL, CHL, and CHP enhanced fullerene C60potential to be used as target drug delivery system with the ability to induce specific intracellular changes in HeLa cancer cells.

Published
2020

3. Synthesis of some steroidal oximes, lactams, thiolactams and their antitumor activities

Author

Krstić, Natalija, Bjelaković, Mira, Žižak, Željko, Pavlović, Mirjana, Juranić, Zorica, Pavlović, Vladimir D., Krstić, Natalija, Bjelaković, Mira, Žižak, Željko, Pavlović, Mirjana, Juranić, Zorica, and Pavlović, Vladimir D.

Abstract

The antiproliferative activity of previously synthesized (Z)-cholest-4-en-6-one oxime (1), (E)-cholest-4-en-6-one oxime (2), 7-aza-B-homocholest-4-en-6-one (3) and 6-aza-B-homocholest-4-en-7-one (4) and newly synthesized 6-thioxo-7-aza-B-homocholest-4-ene (5) and 6-aza-7-thioxo-B-homocholest-4-ene (6) was tested for their possible effects against two human tumor cell lines, cervical carcinoma (HeLa) and chronic myelogenous leukemia (K-562). Compounds 1-6, exerted a dose-dependent antiproliferative effect toward cell lines used in experimental design, showing high selectivity in their action for tumor cells in comparison to normal immunocompetent cells (non-stimulated PBMC and PHA-stimulated PBMC). Compounds 2, 3 and 4 exhibited a very high but selective antitumor activity, by inducing apoptosis in sensitive, for that purpose targeted tumor cell line (HeLa cells). Low toxic effect upon both non-stimulated, and PHA stimulated PBMCs from control, healthy volunteers, has been detected for compounds 1, 2, 3 and 4. The possible reasons for profound differences in the effects of this spectrum of steroidal compounds between tumor cell lines and normal stimulated and non-stimulated PBMCs are discussed. The molecular mechanisms for apoptotic events in HeLa cell line are suggested. The guidelines for further research are underlined.

Published
2007

4. SR-FTIR spectro-microscopic interaction study of biochemical changes in HeLa cells induced by Levan-C 60 , Pullulan-C 60 , and their cholesterol-derivatives.

Author

Nešić MD, Dučić T, Liang X, Algarra M, Mi L, Korićanac L, Žakula J, Kop TJ, Bjelaković MS, Mitrović A, Gojgić Cvijović GD, Stepić M, and Petković M

Subjects
Adsorption, Cell Adhesion, Cell Proliferation, Diphenhydramine chemistry, Hep G2 Cells, Humans, Hydrogels, Lidocaine chemistry, Propranolol chemistry, Spectroscopy, Fourier Transform Infrared, Synchrotrons, Cell Culture Techniques methods, Fructans chemistry, Glucans chemistry, Hyaluronic Acid chemistry, Maleates chemistry
Abstract

Objects of the present study are improved fullerene C 60 drug carrier properties trough encapsulation by microbial polysaccharides, levan (LEV), pullulan (PUL), and their hydrophobized cholesterol-derivatives (CHL and CHP), that show better interaction with cancer cells. The zeta potential, polydispersity index, and the diameter of particles were determined, and their cytotoxicity against three cancer cell lines were tested. Biochemical changes in HeLa cells are analyzed by synchrotron radiation (SR) FTIR spectro-microscopy combined with the principal component analysis (PCA). The most significant changes occur in HeLa cells treated with LEV-C 60 and correspond to the changes in the protein region, i.e. Amide I band, and the changes in the structure of lipid bodies and membrane fluidity are evident. The highest cytotoxicity was also induced by LEV-C 60 . In HeLa cells, cytotoxicity could not be strictly associated with biochemical changes in lipids, proteins and nucleic acids, but these findings are significant contribution to the study of the mechanism of interaction of C 60 -based nanoparticles with cellular biomolecules. In conclusion, LEV, PUL, CHL, and CHP enhanced fullerene C 60 potential to be used as target drug delivery system with the ability to induce specific intracellular changes in HeLa cancer cells., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Published
2020
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5. New androst-4-en-17-spiro-1,3,2-oxathiaphospholanes. Synthesis, assignment of absolute configuration and in vitro cytotoxic and antimicrobial activities.

Author

Krstić NM, Bjelaković MS, Pavlović VD, Robeyns K, Juranić ZD, Matić I, Novaković I, and Sladić DM

Subjects
Androstenes chemistry, Androstenes pharmacology, Animals, Anti-Infective Agents chemistry, Anti-Infective Agents pharmacology, Antineoplastic Agents chemistry, Antineoplastic Agents pharmacology, Artemia drug effects, Candida albicans drug effects, Cell Line, Tumor, Crystallography, X-Ray, Gram-Negative Bacteria drug effects, Gram-Positive Bacteria drug effects, HeLa Cells, Humans, Inhibitory Concentration 50, Magnetic Resonance Spectroscopy methods, Molecular Structure, Saccharomyces cerevisiae drug effects, Androstenes chemical synthesis, Anti-Infective Agents chemical synthesis, Antineoplastic Agents chemical synthesis, Models, Chemical
Abstract

The reactions of 17α-hydroxyprogesterone with Lawesson's reagent (LR) in toluene, CH(2)Cl(2) and/or CCl(4) gave, depending on the duration of the reaction, two diastereoisomeric androst-4-en-17-spiro-1,3,2-oxathiaphospholane-2-sulfide pairs 2a,b and 3a,b in approximately 7:3 ratio, differing in configuration at the phosphorus atom. A parallel analysis of heteronuclear 2D (1)H-(13)C spectra (HSQC and HMBC) and homonuclear 2D spectra (NOESY) enabled complete (1)H and (13)C assignments of each isomer. Also, analysis of NOESY correlations provided evidence for the preferred conformation. X-ray analysis of 3a confirmed the structure and absolute configuration on phosphorus. A pathway for the formation of 1,3,2-oxathiaphospholane ring was proposed. Cytotoxic activity in vitro was tested against three tumor cell lines (human cervix carcinoma HeLa cells and two human breast carcinoma MDA-MB-361 and MDA-MB-453 cells). Compound 3a and mixture 3a,b showed a moderate activity against HeLa and MDA-MB-453 cell lines while against MDA-MB-361 cell line all tested compounds exerted very weak cytotoxic effect. Antimicrobial activity against Gram-positive, Gram-negative bacteria and fungal cells, toxicity to brine shrimp Artemia salina, were evaluated. All tested compounds showed strong antifungal activity., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Published
2012
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6. Synthesis of some steroidal oximes, lactams, thiolactams and their antitumor activities.

Author

Krstić NM, Bjelaković MS, Zizak Z, Pavlović MD, Juranić ZD, and Pavlović VD

Subjects
Antineoplastic Agents chemical synthesis, Antineoplastic Agents chemistry, Apoptosis drug effects, Drug Screening Assays, Antitumor, HeLa Cells, Humans, K562 Cells, Lactams chemical synthesis, Lactams chemistry, Leukocytes, Mononuclear metabolism, Oximes chemical synthesis, Oximes chemistry, Steroids chemical synthesis, Steroids chemistry, Sulfhydryl Compounds chemical synthesis, Sulfhydryl Compounds chemistry, Sulfhydryl Compounds pharmacology, Antineoplastic Agents pharmacology, Cell Proliferation drug effects, Lactams pharmacology, Oximes pharmacology, Steroids pharmacology
Abstract

The antiproliferative activity of previously synthesized (Z)-cholest-4-en-6-one oxime (1), (E)-cholest-4-en-6-one oxime (2), 7-aza-B-homocholest-4-en-6-one (3) and 6-aza-B-homocholest-4-en-7-one (4) and newly synthesized 6-thioxo-7-aza-B-homocholest-4-ene (5) and 6-aza-7-thioxo-B-homocholest-4-ene (6) was tested for their possible effects against two human tumor cell lines, cervical carcinoma (HeLa) and chronic myelogenous leukemia (K-562). Compounds 1-6, exerted a dose-dependent antiproliferative effect toward cell lines used in experimental design, showing high selectivity in their action for tumor cells in comparison to normal immunocompetent cells (non-stimulated PBMC and PHA-stimulated PBMC). Compounds 2, 3 and 4 exhibited a very high but selective antitumor activity, by inducing apoptosis in sensitive, for that purpose targeted tumor cell line (HeLa cells). Low toxic effect upon both non-stimulated, and PHA stimulated PBMCs from control, healthy volunteers, has been detected for compounds 1, 2, 3 and 4. The possible reasons for profound differences in the effects of this spectrum of steroidal compounds between tumor cell lines and normal stimulated and non-stimulated PBMCs are discussed. The molecular mechanisms for apoptotic events in HeLa cell line are suggested. The guidelines for further research are underlined.

Published
2007
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