title: Synthesis, antiproliferative and antibacterial evaluation of C-ring modified colchicine analogues.
abstract: A series of 10 amine derivatives of colchicine have been obtained with high yields by modification at C(10)-OCH3 position of C-ring and characterized by spectroscopic methods. In vitro cytotoxicity has been evaluated against four human tumour cell lines (HL-60, HL-60/vinc, LoVo, LoVo/DX), as well as antibacterial activity against clinical isolates of methicillin-resistant Staphylococcus aureus (MRSA) and Staphylococcus epidermidis (MRSE). From among the compounds tested the most active is colchicine derivative 2h with bis(2-methoxyethyl)amine substituent which is active in nanomolar to submicromolar concentrations and is several times more cytotoxic than cisplatin and doxorubicin. This compound is also effective against the methicillin-resistant Staphylococci strains.
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
authors.affiliation: Faculty of Chemistry, Adam Mickiewicz University, Grunwaldzka 6, 60-780 Poznan, Poland.
authors.forename: Jacek
authors.initials: J
authors.lastname: Rutkowski
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: 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: 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: 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: Faculty of Chemistry, Adam Mickiewicz University, Grunwaldzka 6, 60-780 Poznan, Poland.
authors.forename: Urszula
authors.initials: U
authors.lastname: Majcher
authors.affiliation: Institut für Medizinische Physik und Biophysik Charité, Universitätsmedizin Berlin, Campus Charité Mitte, Charitéplatz 1, 10117 Berlin, Germany.
authors.forename: Franz
authors.initials: F
authors.lastname: Bartl
mesh_terms: D016475:3T3 Cells; D000818:Animals; 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; D003078:Colchicine / Q000031:analogs & derivatives* / Q000737:chemistry; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D018922:HL-60 Cells; D006801:Humans; D055624:Methicillin-Resistant Staphylococcus aureus / Q000187:drug effects*; D051379:Mice; D008807:Mice, Inbred BALB C; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D013212:Staphylococcus epidermidis / Q000187:drug effects*; D013329:Structure-Activity Relationship
chemical_list: D000900:Anti-Bacterial Agents; D000970:Antineoplastic Agents; D003078:Colchicine
keywords: Antibacterial activity; Anticancer activity; Antimitotic agent; MRSA; MRSE