Caffeine-hydrazones as anticancer agents with pronounced selectivity toward T-lymphoblastic leukaemia cells.
We report design and synthesis of set of novel anticancer agents based on caffeine-hydrazones bearing 2-hydroxyaryl- or 2-N-heteroaryl moiety. Anticancer activity evaluation using seven cancer cell lines and two non-malignant cell lines demonstrated that several derivatives display significant anticancer activity and great selectivity index toward T-lymphoblastic leukaemia cells. In general, hydrazones bearing 2-N-heteroaryl moiety are more active and selective than those with 2-hydroxyaryl moiety. Tested compounds exhibit dose-dependent inhibition of both RNA and DNA synthesis, with some exceptions. Antimicrobial activities were tested on set of twelve bacterial and yeast strains, however prepared compounds were not active, suggesting for a molecular target specific for eukaryotic cells.
Department of Analytical Chemistry, Faculty of Chemical Engineering, University of Chemistry and Technology, Technická 5, 166 28 Prague 6, Czech Republic.
Robert
R
Kaplánek
Department of Analytical Chemistry, Faculty of Chemical Engineering, University of Chemistry and Technology, Technická 5, 166 28 Prague 6, Czech Republic.
Milan
M
Jakubek
Department of Analytical Chemistry, Faculty of Chemical Engineering, University of Chemistry and Technology, Technická 5, 166 28 Prague 6, Czech Republic.
Jakub
J
Rak
Department of Analytical Chemistry, Faculty of Chemical Engineering, University of Chemistry and Technology, Technická 5, 166 28 Prague 6, Czech Republic.
Zdeněk
Z
Kejík
Department of Analytical Chemistry, Faculty of Chemical Engineering, University of Chemistry and Technology, Technická 5, 166 28 Prague 6, Czech Republic.
Martin
M
Havlík
Department of Analytical Chemistry, Faculty of Chemical Engineering, University of Chemistry and Technology, Technická 5, 166 28 Prague 6, Czech Republic.
Bohumil
B
Dolenský
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.
Ivo
I
Frydrych
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 and Translational Medicine, Palacky University and University Hospital in Olomouc, Faculty of Medicine and Dentistry, Hněvotínská 5, 775 15 Olomouc, Czech Republic; Department of Microbiology, Palacky University and University Hospital in Olomouc, Faculty of Medicine and Dentistry, Hněvotínská 5, 775 15 Olomouc, Czech Republic.
Milan
M
Kolář
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.
Kateřina
K
Bogdanová
Institute of Molecular Genetics, Academy of Sciences of the Czech Republic, Vídeňská 1083, 142 20 Prague 4, Czech Republic.
Jarmila
J
Králová
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. Electronic address: Petr.Dzubak@upol.cz.
Petr
P
Džubák
Department of Analytical Chemistry, Faculty of Chemical Engineering, University of Chemistry and Technology, Technická 5, 166 28 Prague 6, Czech Republic. Electronic address: Vladimir.Kral@vscht.cz.
Vladimír
V
Král
D000890:Anti-Infective Agents / Q000737:chemistry / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001419:Bacteria / Q000187:drug effects; D002110:Caffeine / Q000737:chemistry* / Q000494:pharmacology*; D002460:Cell Line; D045744:Cell Line, Tumor; D005658:Fungi / Q000187:drug effects; D006801:Humans; D006835:Hydrazones / Q000737:chemistry* / Q000494:pharmacology*; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy*; D013329:Structure-Activity Relationship
D000890:Anti-Infective Agents; D000970:Antineoplastic Agents; D006835:Hydrazones; D002110:Caffeine
Anticancer agents; Caffeine–hydrazones; Cancer treatment; Leukaemia; Selectivity