title: Synthesis and biological activity of salinomycin conjugates with floxuridine.
abstract: As part of our program to develop anticancer agents, we have synthesized new compounds, which are conjugates between well-known anticancer drug, floxuridine and salinomycin which is able to selectivity kill cancer stem cells. The conjugates were obtained in two ways i.e. by copper(I) catalysed click Huisgen cycloaddition reaction performed between 3'-azido-2',3'-dideoxy-5-fluorouridine and salinomycin propargyl amide, and by the ester synthesis starting from salinomycin and floxuridine under mild condition. The compounds obtained were characterized by spectroscopic methods and evaluated for their in vitro cytotoxicity against seven human cancer cell lines as well as antibacterial activity against clinical isolates of methicillin-resistant Staphylococcus aureus (MRSA) and Staphylococcus epidermidis (MRSE). The conjugate obtained by esterification reaction showed a significantly higher antiproliferative activity against the drug-resistant cancer cells and lower toxicity than those of salinomycin and floxuridine towards normal cells, as well as standard anticancer drugs, such as cisplatin and doxorubicin. The conjugate compound revealed also moderate activity against MRSA and MRSE bacterial strains. Very high activity of floxuridine and 5-fluorouracil against MRSA and MRSE has been also observed.
authors: Faculty of Chemistry, Adam Mickiewicz University, Umultowska 89b, 61-614 Poznań, Poland. Electronic address: adhucz@amu.edu.pl.
authors: Adam
authors: A
authors: Huczyński
authors: Faculty of Chemistry, Adam Mickiewicz University, Umultowska 89b, 61-614 Poznań, Poland.
authors: Michał
authors: M
authors: Antoszczak
authors: Faculty of Chemistry, Adam Mickiewicz University, Umultowska 89b, 61-614 Poznań, Poland.
authors: Natalia
authors: N
authors: Kleczewska
authors: Faculty of Chemistry, Adam Mickiewicz University, Umultowska 89b, 61-614 Poznań, Poland.
authors: Marta
authors: M
authors: Lewandowska
authors: Ludwik Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Rudolfa Weigla 12, 53-114 Wrocław, Poland.
authors: Ewa
authors: E
authors: Maj
authors: Medical University of Warsaw, Department of Pharmaceutical Microbiology, Oczki 3, 02-007 Warsaw, Poland.
authors: Joanna
authors: J
authors: Stefańska
authors: Ludwik Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Rudolfa Weigla 12, 53-114 Wrocław, Poland.
authors: Joanna
authors: J
authors: Wietrzyk
authors: Institute of Low Temperature and Structure Research, Polish Academy of Sciences, PO Box 1410, 50-950 Wrocław, Poland.
authors: Jan
authors: J
authors: Janczak
authors: Faculty of Chemistry, Adam Mickiewicz University, Umultowska 89b, 61-614 Poznań, Poland.
authors: Lech
authors: L
authors: Celewicz
mesh_terms: D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D015195:Drug Design; D005467:Floxuridine / Q000737:chemistry* / Q000494:pharmacology; D006801:Humans; D055624:Methicillin-Resistant Staphylococcus aureus / Q000187:drug effects; D015394:Molecular Structure; D011714:Pyrans / Q000737:chemistry* / Q000494:pharmacology; D013212:Staphylococcus epidermidis / Q000187:drug effects; D013329:Structure-Activity Relationship; D000095662:Polyether Polyketides
chemical_list: D000900:Anti-Bacterial Agents; D000970:Antineoplastic Agents; D005467:Floxuridine; D011714:Pyrans; C010327:salinomycin; D000095662:Polyether Polyketides
keywords: Antibacterial activity; Anticancer activity; Conjugation; Hybrid compound