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

Autor: Jana Janockova, Jan Korabecny, Jana Plsikova, Katerina Babkova, Eva Konkolova, Dana Kucerova, Jana Vargova, Jan Koval, Rastislav Jendzelovsky, Peter Fedorocko, Jana Kasparkova, Viktor Brabec, Jan Rosocha, Ondrej Soukup, Slavka Hamulakova, Kamil Kuca, Maria Kozurkova
Jazyk: angličtina
Rok vydání: 2019
Předmět:
Zdroj: Journal of Enzyme Inhibition and Medicinal Chemistry, Vol 34, Iss 1, Pp 877-897 (2019)
Druh dokumentu: article
ISSN: 1475-6366
1475-6374
14756366
DOI: 10.1080/14756366.2019.1593159
Popis: 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.
Databáze: Directory of Open Access Journals
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