Synthesis and biological activity evaluation of hydrazone derivatives based on a Tröger's base skeleton.
We report the design and synthesis of novel anticancer agents based on bis-hydrazones separated by a rigid Tröger's base skeleton. This novel approach combines a biologically active moiety (hydrazone) with this scaffold (Tröger's base) to construct DNA intercalators. Evaluation of the anticancer activity of these agents using seven cancer cell lines and two healthy cell lines found that several derivatives had potent anticancer activity and excellent selectivity indexes toward cancer cells. The antimicrobial activities were tested on a set of thirteen bacterial stains, but the prepared compounds were not active. Complexation studies using biologically important metal ions demonstrated that these compounds are able to bind Cu(2+), Fe(3+), Co(2+), Ni(2+) and Zn(2+). DNA intercalation studies showed that the compounds themselves do not interact with DNA, but their metallocomplexes do interact, most likely via intercalation into DNA.
Department of Analytical Chemistry, Faculty of Chemical Engineering, University of Chemical Technology, Technická 5, 166 28 Prague 6, Czech Republic.
Robert
R
Kaplánek
Department of Analytical Chemistry, Faculty of Chemical Engineering, University of Chemical Technology, Technická 5, 166 28 Prague 6, Czech Republic.
Martin
M
Havlík
Department of Analytical Chemistry, Faculty of Chemical Engineering, University of Chemical Technology, Technická 5, 166 28 Prague 6, Czech Republic.
Bohumil
B
Dolenský
Department of Analytical Chemistry, Faculty of Chemical Engineering, University of Chemical Technology, Technická 5, 166 28 Prague 6, Czech Republic.
Jakub
J
Rak
Institute of Molecular and Translational Medicine, Palacky University and University Hospital in Olomouc, Faculty of Medicine and Dentistry, Hněvotínská 5, 775 15 Olomouc, Czech Republic.
Petr
P
Džubák
Institute of Molecular and Translational Medicine, Palacky University and University Hospital in Olomouc, Faculty of Medicine and Dentistry, Hněvotínská 5, 775 15 Olomouc, Czech Republic.
Petr
P
Konečný
Institute of Molecular and Translational Medicine, Palacky University and University Hospital in Olomouc, Faculty of Medicine and Dentistry, Hněvotínská 5, 775 15 Olomouc, Czech Republic.
Marián
M
Hajdúch
Institute of Molecular Genetics, Academy of Sciences of the Czech Republic, Vídeňská 1083, 142 20 Prague 4, Czech Republic.
Jarmila
J
Králová
Department of Analytical Chemistry, Faculty of Chemical Engineering, University of Chemical Technology, Technická 5, 166 28 Prague 6, Czech Republic. Electronic address: Vladimir.Kral@vscht.cz.
Vladimír
V
Král
D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D004353:Drug Evaluation, Preclinical / Q000379:methods; D045325:HCT116 Cells; D006801:Humans; D006835:Hydrazones / Q000138:chemical synthesis* / Q000494:pharmacology; D020014:K562 Cells
D000970:Antineoplastic Agents; D006835:Hydrazones
Anticancer agents; Cancer treatment; Complexation studies; Hydrazone; Tröger’s base