TY  - THES
AU  - Lazić, Jelena
PY  - 2022
UR  - https://repozitorij.ung.si/IzpisGradiva.php?id=7664&lang=eng
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1793
AB  - Prodigiosins (PGs) are a class of bacterial secondary metabolites with remarkable biological activities and colour. In this study, optimised fermentative production of prodigiosin (PG) using waste processed meat as a substrate has been achieved to levels of 83.1 ± 3.0 mg/L from a commercially available Serratia marcescens ATCC 27117 strain within 12 h. Methods were established for the reliable PG extraction from both the bacterial cell pellet and the culture supernatant, while gravitation column chromatography was used to obtain pure bacterial PG. The structure of the isolated PG was optimised by environmentally acceptable oxidative bromination reactions, obtaining mono- and dibrominated derivatives (PG-Br and PG-Br2). Chemical structures were confirmed by structural characterisation using nuclear magnetic resonance (NMR) spectroscopy and mass spectrometry (MS), showing that PG-Br is a mixture of two monobrominated isomers in approximately equal ratios, while PG-Br2 was afforded as a pure derivative. PG and its brominated derivatives (Br-derivatives) showed anticancer potential with half-maximal inhibitory concentration (IC50) values ranging from 0.62 to 17.00 μg/mL on four tested cancer cell lines (A549 lung, A375 skin, MDA-MB-231 breast, HCT116 colon) and an induction of early apoptosis, but low selectivity against healthy cell lines (MRC-5 lung fibroblasts and HaCaT skin keratinocytes). All three PG, PG-Br and PG-Br2 compounds did not affect roundworms (Caenorhabditis elegans) at concentrations up to 50 μg/mL. However, an improved toxicity profile of Br-derivatives in comparison to the parent PG was observed in vivo using zebrafish (Danio rerio) model system, when 10 μg/mL applied at 6 h post fertilisation caused death rate of 100, 30 and 0% by PG, PG-Br and PG-Br2, respectively, which is a significant finding for further structural optimisations of bacterial PGs.
AB  - Prodigiozini (PG) so razred obarvanih sekundarnih bakterijskih metabolitov z izjemno biološko aktivnostjo. V doktorski raziskovalni nalogi smo za proizvodnjo prodigiozina uporabili komercialni sev bakterije Serratia marcescens ATCC 27117, kot substrat za fermentacijo pa odpadne produkte procesiranja mesa. Na ta način smo pridobili do 83.1 ± 3.0 prodigiozina v 12-ih urah fermentacije. V nadaljevanju smo vzpostavili metode za ekstrakcijo PS tako iz peleta bakterijskih celic kot tudi iz supernatanta bakterijske kulture. Za pridobitev čistega bakterijskega PG smo uporabili gravitacijsko kolonsko kromatografijo.
Strukturo izoliranega PG smo optimizirali z okolju prijazno metodo oksidativnega bromiranja, pri čemer smo dobili mono- in di-bromirane derivate (PG-Br in PG-Br2). Strukturna karakterizacija bromiranih spojin s pomočjo jedrske magnetne resonance (NMR) in masne spektrometrije (MS) je pokazala, da je PG-Br zmes dveh mono-bromiranih izomer v približno enakih razmerjih, medtem ko je bil PG-Br2 pridobljen kot čisti derivat.
PG in njegove bromirane derivate smo testirali na  štirih rakavih celičnih linijah (A549 – pljučne celice, A375 – kožne celice, MDA-MB-231 – celice raka na prsih in HCT116 – črevesne celice). Potrdili smo antitumorske lastnosti PG in njegovih bromiranih derivatov s polovičnimi maksimalnimi inhibitornimi koncentracijami (IC50) v razponu od 0,62 do 17,00 µg/mL ter indukcijo zgodnje apoptoze, vendar hkrati tudi nizko selektivnost proti zdravim celičnim linijam (MRC-5 - pljučni fibroblasti in HaCaT - kožni keratinociti). Nobena od testiranih PG, PG-Br in PG-Br2 spojin ni imela opaznega vpliva na gliste Caenorhabditis elegans pri koncentracijah do 50 µg/mL. Ugotovili pa smo manjšo toksičnost bromiranih derivatov PG v primerjavi z matičnim PG v modelnem sistemu rib cebric (Danio rerio) in vivo. Pri cebricah, ki so bile 6 ur po oploditvi izpostavljene 10 µg/mL PG, PG-Br oziroma PG-Br2, smo ugotovili 100%, 30% in 0% smrtnost, kar je pomembna ugotovitev za nadaljnjo strukturno optimizacijo bakterijskih PG.
PB  - University of Nova Gorica
T1  - Structure optimisation of biopigment prodigiosin from Serratia marcescens ATCC 27117 and antimicrobial and anticancer properties of novel halogenated derivatives
T1  - Strukturna optimizacija biopigmenta prodigiozin iz bakterije Serratia marcescens ATCC 27117 ter antimikrobne in antitumorske lastnosti novih halogeniranih derivatov
UR  - https://hdl.handle.net/21.15107/rcub_imagine_1793
ER  - 

@phdthesis{
author = "Lazić, Jelena",
year = "2022",
abstract = "Prodigiosins (PGs) are a class of bacterial secondary metabolites with remarkable biological activities and colour. In this study, optimised fermentative production of prodigiosin (PG) using waste processed meat as a substrate has been achieved to levels of 83.1 ± 3.0 mg/L from a commercially available Serratia marcescens ATCC 27117 strain within 12 h. Methods were established for the reliable PG extraction from both the bacterial cell pellet and the culture supernatant, while gravitation column chromatography was used to obtain pure bacterial PG. The structure of the isolated PG was optimised by environmentally acceptable oxidative bromination reactions, obtaining mono- and dibrominated derivatives (PG-Br and PG-Br2). Chemical structures were confirmed by structural characterisation using nuclear magnetic resonance (NMR) spectroscopy and mass spectrometry (MS), showing that PG-Br is a mixture of two monobrominated isomers in approximately equal ratios, while PG-Br2 was afforded as a pure derivative. PG and its brominated derivatives (Br-derivatives) showed anticancer potential with half-maximal inhibitory concentration (IC50) values ranging from 0.62 to 17.00 μg/mL on four tested cancer cell lines (A549 lung, A375 skin, MDA-MB-231 breast, HCT116 colon) and an induction of early apoptosis, but low selectivity against healthy cell lines (MRC-5 lung fibroblasts and HaCaT skin keratinocytes). All three PG, PG-Br and PG-Br2 compounds did not affect roundworms (Caenorhabditis elegans) at concentrations up to 50 μg/mL. However, an improved toxicity profile of Br-derivatives in comparison to the parent PG was observed in vivo using zebrafish (Danio rerio) model system, when 10 μg/mL applied at 6 h post fertilisation caused death rate of 100, 30 and 0% by PG, PG-Br and PG-Br2, respectively, which is a significant finding for further structural optimisations of bacterial PGs., Prodigiozini (PG) so razred obarvanih sekundarnih bakterijskih metabolitov z izjemno biološko aktivnostjo. V doktorski raziskovalni nalogi smo za proizvodnjo prodigiozina uporabili komercialni sev bakterije Serratia marcescens ATCC 27117, kot substrat za fermentacijo pa odpadne produkte procesiranja mesa. Na ta način smo pridobili do 83.1 ± 3.0 prodigiozina v 12-ih urah fermentacije. V nadaljevanju smo vzpostavili metode za ekstrakcijo PS tako iz peleta bakterijskih celic kot tudi iz supernatanta bakterijske kulture. Za pridobitev čistega bakterijskega PG smo uporabili gravitacijsko kolonsko kromatografijo.
Strukturo izoliranega PG smo optimizirali z okolju prijazno metodo oksidativnega bromiranja, pri čemer smo dobili mono- in di-bromirane derivate (PG-Br in PG-Br2). Strukturna karakterizacija bromiranih spojin s pomočjo jedrske magnetne resonance (NMR) in masne spektrometrije (MS) je pokazala, da je PG-Br zmes dveh mono-bromiranih izomer v približno enakih razmerjih, medtem ko je bil PG-Br2 pridobljen kot čisti derivat.
PG in njegove bromirane derivate smo testirali na  štirih rakavih celičnih linijah (A549 – pljučne celice, A375 – kožne celice, MDA-MB-231 – celice raka na prsih in HCT116 – črevesne celice). Potrdili smo antitumorske lastnosti PG in njegovih bromiranih derivatov s polovičnimi maksimalnimi inhibitornimi koncentracijami (IC50) v razponu od 0,62 do 17,00 µg/mL ter indukcijo zgodnje apoptoze, vendar hkrati tudi nizko selektivnost proti zdravim celičnim linijam (MRC-5 - pljučni fibroblasti in HaCaT - kožni keratinociti). Nobena od testiranih PG, PG-Br in PG-Br2 spojin ni imela opaznega vpliva na gliste Caenorhabditis elegans pri koncentracijah do 50 µg/mL. Ugotovili pa smo manjšo toksičnost bromiranih derivatov PG v primerjavi z matičnim PG v modelnem sistemu rib cebric (Danio rerio) in vivo. Pri cebricah, ki so bile 6 ur po oploditvi izpostavljene 10 µg/mL PG, PG-Br oziroma PG-Br2, smo ugotovili 100%, 30% in 0% smrtnost, kar je pomembna ugotovitev za nadaljnjo strukturno optimizacijo bakterijskih PG.",
publisher = "University of Nova Gorica",
title = "Structure optimisation of biopigment prodigiosin from Serratia marcescens ATCC 27117 and antimicrobial and anticancer properties of novel halogenated derivatives, Strukturna optimizacija biopigmenta prodigiozin iz bakterije Serratia marcescens ATCC 27117 ter antimikrobne in antitumorske lastnosti novih halogeniranih derivatov",
url = "https://hdl.handle.net/21.15107/rcub_imagine_1793"
}

Lazić, J.. (2022). Structure optimisation of biopigment prodigiosin from Serratia marcescens ATCC 27117 and antimicrobial and anticancer properties of novel halogenated derivatives. 
University of Nova Gorica..
https://hdl.handle.net/21.15107/rcub_imagine_1793

Lazić J. Structure optimisation of biopigment prodigiosin from Serratia marcescens ATCC 27117 and antimicrobial and anticancer properties of novel halogenated derivatives. 2022;.
https://hdl.handle.net/21.15107/rcub_imagine_1793 .

Lazić, Jelena, "Structure optimisation of biopigment prodigiosin from Serratia marcescens ATCC 27117 and antimicrobial and anticancer properties of novel halogenated derivatives" (2022),
https://hdl.handle.net/21.15107/rcub_imagine_1793 .

TY  - JOUR
AU  - Lazić, Jelena
AU  - Škaro Bogojević, Sanja
AU  - Vojnović, Sandra
AU  - Aleksić, Ivana
AU  - Milivojević, Dušan
AU  - Kretzschmar, Martin
AU  - Gulder, Tanja
AU  - Petković, Milos
AU  - Nikodinović-Runić, Jasmina
PY  - 2022
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1591
AB  - Prodigiosins (prodiginines) are a class of bacterial secondary metabolites with remarkable biological activities and color. In this study, optimized production, purification, and characterization of prodigiosin (PG) from easily accessible Serratia marcescens ATCC 27117 strain has been achieved to levels of 14 mg/L of culture within 24 h. Furthermore, environmentally friendly bromination of produced PG was used to afford both novel mono- and dibrominated derivatives of PG. PG and its Br derivatives showed anticancer potential with IC50 values range 0.62-17.00 mu g/mL for all tested cancer cell lines and induction of apoptosis but low selectivity against healthy cell lines. All compounds did not affect Caenorhabditis elegans at concentrations up to 50 mu g/mL. However, an improved toxicity profile of Br derivatives in comparison to parent PG was observed in vivo using zebrafish (Danio rerio) model system, when 10 mu g/mL applied at 6 h post fertilization caused death rate of 100%, 30% and 0% by PG, PG-Br, and PG-Br-2,Br- respectively, which is a significant finding for further structural optimizations of bacterial prodigiosins. The drug-likeness of PG and its Br derivatives was examined, and the novel Br derivatives obey the Lipinski's "rule of five", with an exemption of being more lipophilic than PG, which still makes them good targets for further structural optimization.
PB  - MDPI, Basel
T2  - Molecules
T1  - Synthesis, Anticancer Potential and Comprehensive Toxicity Studies of Novel Brominated Derivatives of Bacterial Biopigment Prodigiosin from Serratia marcescens ATCC 27117
IS  - 12
VL  - 27
DO  - 10.3390/molecules27123729
ER  - 

@article{
author = "Lazić, Jelena and Škaro Bogojević, Sanja and Vojnović, Sandra and Aleksić, Ivana and Milivojević, Dušan and Kretzschmar, Martin and Gulder, Tanja and Petković, Milos and Nikodinović-Runić, Jasmina",
year = "2022",
abstract = "Prodigiosins (prodiginines) are a class of bacterial secondary metabolites with remarkable biological activities and color. In this study, optimized production, purification, and characterization of prodigiosin (PG) from easily accessible Serratia marcescens ATCC 27117 strain has been achieved to levels of 14 mg/L of culture within 24 h. Furthermore, environmentally friendly bromination of produced PG was used to afford both novel mono- and dibrominated derivatives of PG. PG and its Br derivatives showed anticancer potential with IC50 values range 0.62-17.00 mu g/mL for all tested cancer cell lines and induction of apoptosis but low selectivity against healthy cell lines. All compounds did not affect Caenorhabditis elegans at concentrations up to 50 mu g/mL. However, an improved toxicity profile of Br derivatives in comparison to parent PG was observed in vivo using zebrafish (Danio rerio) model system, when 10 mu g/mL applied at 6 h post fertilization caused death rate of 100%, 30% and 0% by PG, PG-Br, and PG-Br-2,Br- respectively, which is a significant finding for further structural optimizations of bacterial prodigiosins. The drug-likeness of PG and its Br derivatives was examined, and the novel Br derivatives obey the Lipinski's "rule of five", with an exemption of being more lipophilic than PG, which still makes them good targets for further structural optimization.",
publisher = "MDPI, Basel",
journal = "Molecules",
title = "Synthesis, Anticancer Potential and Comprehensive Toxicity Studies of Novel Brominated Derivatives of Bacterial Biopigment Prodigiosin from Serratia marcescens ATCC 27117",
number = "12",
volume = "27",
doi = "10.3390/molecules27123729"
}

Lazić, J., Škaro Bogojević, S., Vojnović, S., Aleksić, I., Milivojević, D., Kretzschmar, M., Gulder, T., Petković, M.,& Nikodinović-Runić, J.. (2022). Synthesis, Anticancer Potential and Comprehensive Toxicity Studies of Novel Brominated Derivatives of Bacterial Biopigment Prodigiosin from Serratia marcescens ATCC 27117. in Molecules
MDPI, Basel., 27(12).
https://doi.org/10.3390/molecules27123729

Lazić J, Škaro Bogojević S, Vojnović S, Aleksić I, Milivojević D, Kretzschmar M, Gulder T, Petković M, Nikodinović-Runić J. Synthesis, Anticancer Potential and Comprehensive Toxicity Studies of Novel Brominated Derivatives of Bacterial Biopigment Prodigiosin from Serratia marcescens ATCC 27117. in Molecules. 2022;27(12).
doi:10.3390/molecules27123729 .

Lazić, Jelena, Škaro Bogojević, Sanja, Vojnović, Sandra, Aleksić, Ivana, Milivojević, Dušan, Kretzschmar, Martin, Gulder, Tanja, Petković, Milos, Nikodinović-Runić, Jasmina, "Synthesis, Anticancer Potential and Comprehensive Toxicity Studies of Novel Brominated Derivatives of Bacterial Biopigment Prodigiosin from Serratia marcescens ATCC 27117" in Molecules, 27, no. 12 (2022),
https://doi.org/10.3390/molecules27123729 . .