Synthesis, Anticancer Potential and Comprehensive Toxicity Studies of Novel Brominated Derivatives of Bacterial Biopigment Prodigiosin from Serratia marcescens ATCC 27117
Authors
Lazić, JelenaŠkaro Bogojević, Sanja
Vojnović, Sandra
Aleksić, Ivana
Milivojević, Dušan
Kretzschmar, Martin
Gulder, Tanja
Petković, Milos
Nikodinović-Runić, Jasmina
Article (Published version)
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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% an...d 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.
Keywords:
zebrafish / Serratia / prodigiosin / halogenation / embryotoxicity / bromination / anticancer activitySource:
Molecules, 2022, 27, 12Publisher:
- MDPI, Basel
Funding / projects:
- Ministry of Science, Technological Development and Innovation of the Republic of Serbia, institutional funding - 200042 (University of Belgrade, Institute of Molecular Genetics and Genetic Engineering) (RS-MESTD-inst-2020-200042)
- Science Fund of the Republic of Serbia, IDEJE [7730810]
- Deutscher Akademischer Austauschdienst e.V. (DAAD) [57381332]
- Emmy-Noether program of the German Research Foundation [GU 1134/3]
DOI: 10.3390/molecules27123729
ISSN: 1420-3049
WoS: 000815924900001
Scopus: 2-s2.0-85132069920
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Institut za molekularnu genetiku i genetičko inženjerstvoTY - 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 . .