In vitro investigating of anticancer activity of new 7-MEOTA-tacrine heterodimers

Journal of Enzyme Inhibition and Medicinal Chemistry

Jan Rosocha¹  Kamil Kuca²  Ondrej Soukup³  Jan Korabecny³  Katerina Babkova³  Eva Konkolova⁴  Jana Plsikova⁵  Maria Kozurkova⁶  Jana Janockova⁶  Viktor Brabec⁷  Jana Kasparkova⁷  Jan Koval⁸  Jana Vargova⁸  Peter Fedorocko⁸  Rastislav Jendzelovsky⁸  Dana Kucerova⁸  Slavka Hamulakova⁹ 

[1] Associated Tissue Bank, Faculty of Medicine, P.J. Šafárik University, Kosice, Slovak Republic;Biomedical Research Center, University Hospital Hradec Kralove, Hradec Kralove, Czech Republic;Biomedical Research Center, University Hospital Hradec Kralove, Hradec Kralove, Czech Republic;Department of Toxicology and Military Pharmacy, Faculty of Military Health Sciences, University of Defence, Hradec Kralove, Czech Republic;Department of Biochemistry, Institute of Chemistry, Faculty of Science, P. J. Šafárik University, Kosice, Slovak Republic;Department of Biochemistry, Institute of Chemistry, Faculty of Science, P. J. Šafárik University, Kosice, Slovak Republic;Associated Tissue Bank, Faculty of Medicine, P.J. Šafárik University, Kosice, Slovak Republic;Department of Biochemistry, Institute of Chemistry, Faculty of Science, P. J. Šafárik University, Kosice, Slovak Republic;Biomedical Research Center, University Hospital Hradec Kralove, Hradec Kralove, Czech Republic;Department of Biophysics, Faculty of Science, Palacke University, Olomouc, Czech Republic;Department of Cellular Biology, Institute of Biology and Ecology, Faculty of Science, P. J. Šafárik University, Kosice, Slovak Republic;Department of Organic Chemistry, Institute of Chemistry, Faculty of Science, P. J. Šafárik University, Kosice, Slovak Republi;

关键词: 7-MEOTA-tacrine heterodimers;    calf thymus DNA;    topoisomerases;    HL-60;    human dermal fibroblasts;   

DOI  :  10.1080/14756366.2019.1593159

来源: publisher

【 摘 要 】

A combination of biochemical, biophysical and biological techniques was used to study calf thymus DNA interaction with newly synthesized 7-MEOTA-tacrine thiourea 12–17 and urea heterodimers 18–22, and to measure interference with type I and II topoisomerases. Their biological profile was also inspected in vitro on the HL-60 cell line using different flow cytometric techniques (cell cycle distribution, detection of mitochondrial membrane potential dissipation, and analysis of metabolic activity/viability). The compounds exhibited a profound inhibitory effect on topoisomerase activity (e.g. compound 22 inhibited type I topoisomerase at 1 µM concentration). The treatment of HL-60 cells with the studied compounds showed inhibition of cell growth especially with hybrids containing thiourea (14–17) and urea moieties (21 and 22). Moreover, treatment of human dermal fibroblasts with the studied compounds did not indicate significant cytotoxicity. The observed results suggest beneficial selectivity of the heterodimers as potential drugs to target cancer cells.

【 授权许可】

CC BY