title: Synthesis, cytotoxicity and antibacterial activity of new esters of polyether antibiotic - salinomycin.
abstract: A series of 12 novel ester derivatives of naturally occurring polyether antibiotic - salinomycin were synthesized, characterised by spectroscopic method and evaluated for their in vitro antibacterial activity and cytotoxicity. The new esters were demonstrated to form complexes with monovalent and divalent metal cation of 1:1 stoichiometry in contrast to the salinomycin which forms only complexes with monovalent cations. All the obtained compounds show potent antiproliferative activity against human cancer cell lines and a good selectivity index for cancer versus mammalian cells. Additionally, 3 compounds showed higher antiproliferative activity against the drug-resistant cancer cells and lower toxicity towards normal cells than those of unmodified salinomycin and standard anticancer drugs such as cisplatin and doxorubicin. Some of the synthesized compounds showed good inhibitory activity against Staphylococcus strains and clinical isolates of methicillin-resistant Staphylococcus aureus (MRSA) and Staphylococcus epidermidis (MRSE). These studies show that salinomycin esters are interesting scaffolds for the development of novel anticancer and Gram-positive antibacterial agents.
authors.affiliation: Faculty of Chemistry, Adam Mickiewicz University, Grunwaldzka 6, 60-780 Poznan, Poland.
authors.forename: Michał
authors.initials: M
authors.lastname: Antoszczak
authors.affiliation: Faculty of Chemistry, Adam Mickiewicz University, Grunwaldzka 6, 60-780 Poznan, Poland.
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Popiel
authors.affiliation: Medical University of Warsaw, Department of Pharmaceutical Microbiology, Oczki 3, 02-007 Warsaw, Poland.
authors.forename: Joanna
authors.initials: J
authors.lastname: Stefańska
authors.affiliation: Ludwik Hierszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Rudolfa Weigla 12, 53-114 Wrocław, Poland.
authors.forename: Joanna
authors.initials: J
authors.lastname: Wietrzyk
authors.affiliation: Ludwik Hierszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Rudolfa Weigla 12, 53-114 Wrocław, Poland.
authors.forename: Ewa
authors.initials: E
authors.lastname: Maj
authors.affiliation: Institute of Low Temperature and Structure Research, Polish Academy of Sciences, PO Box 1410, 50-950 Wrocław, Poland.
authors.forename: Jan
authors.initials: J
authors.lastname: Janczak
authors.affiliation: Faculty of Chemistry, Adam Mickiewicz University, Grunwaldzka 6, 60-780 Poznan, Poland.
authors.forename: Greta
authors.initials: G
authors.lastname: Michalska
authors.affiliation: Faculty of Chemistry, Adam Mickiewicz University, Grunwaldzka 6, 60-780 Poznan, Poland.
authors.forename: Bogumil
authors.initials: B
authors.lastname: Brzezinski
authors.affiliation: Faculty of Chemistry, Adam Mickiewicz University, Grunwaldzka 6, 60-780 Poznan, Poland. Electronic address: adhucz@amu.edu.pl.
authors.forename: Adam
authors.initials: A
authors.lastname: Huczyński
mesh_terms: D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D004354:Drug Screening Assays, Antitumor; D004952:Esters / Q000737:chemistry; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D055624:Methicillin-Resistant Staphylococcus aureus / Q000187:drug effects; D008826:Microbial Sensitivity Tests; D008958:Models, Molecular; D011714:Pyrans / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D013212:Staphylococcus epidermidis / Q000187:drug effects; D013329:Structure-Activity Relationship; D000095662:Polyether Polyketides
chemical_list: D000900:Anti-Bacterial Agents; D004952:Esters; D011714:Pyrans; C010327:salinomycin; D000095662:Polyether Polyketides
keywords: Antibacterial activity; Anticancer activity; MRSA; MRSE; Salinomycin