1. Synthesis, Anticancer Potential and Comprehensive Toxicity Studies of Novel Brominated Derivatives of Bacterial Biopigment Prodigiosin from Serratia marcescens ATCC 27117
- Author
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Lazic Jelena, Bogojevic Skaro Sanja, Vojnovic Sandra, Aleksic Ivana, Milivojevic Dusan, Kretzschmar Martin, Gulder Tanja, Petkovic Milos, and Nikodinovic Runic Jasmina
- Subjects
prodigiosin ,Serratia ,halogenation ,bromination ,anticancer activity ,embryotoxicity ,zebrafish - 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 accessibleSerratia marcescensATCC 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 IC50values range 0.62–17.00 µg/mL for all tested cancer cell lines and induction of apoptosis but low selectivity against healthy cell lines. All compounds did not affectCaenorhabditiselegansat concentrations up to 50 µg/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 µg/mL applied at 6 h post fertilization caused death rate of 100%, 30% and 0% by PG, PG-Br, and PG-Br2,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.
- Published
- 2022