Tacrine-Coumarin Derivatives as Topoisomerase Inhibitors with Antitumor Effects on A549 Human Lung Carcinoma Cancer Cell Lines

0541456 - ÚOCHB 2022 RIV CH eng J - Článek v odborném periodiku
Konkoľová, Eva - Hudáčová, M. - Hamuľaková, S. - Jendželovský, R. - Vargová, J. - Ševc, J. - Fedoročko, P. - Kožurková, M.
Tacrine-Coumarin Derivatives as Topoisomerase Inhibitors with Antitumor Effects on A549 Human Lung Carcinoma Cancer Cell Lines.
Molecules. Roč. 26, č. 4 (2021), č. článku 1133. E-ISSN 1420-3049
Institucionální podpora: RVO:61388963
Klíčová slova: A549 * DNA * cytotoxicity * lung carcinoma cells * tacrine-coumarin derivatives * topoisomerases I, II
Obor OECD: Biochemistry and molecular biology
Impakt faktor: 4.927, rok: 2021
Způsob publikování: Open access
https://doi.org/10.3390/molecules26041133

A549 human lung carcinoma cell lines were treated with a series of new drugs with both tacrine and coumarin pharmacophores (derivatives 1a–2c) in order to test the compounds’ ability to inhibit both cancer cell growth and topoisomerase I and II activity. The ability of human topoisomerase I (hTOPI) and II to relax supercoiled plasmid DNA in the presence of various concentrations of the tacrine-coumarin hybrid molecules was studied with agarose gel electrophoresis. The biological activities of the derivatives were studied using MTT assays, clonogenic assays, cell cycle analysis and quantification of cell number and viability. The content and localization of the derivatives in the cells were analysed using flow cytometry and confocal microscopy. All of the studied compounds were found to have inhibited topoisomerase I activity completely. The effect of the tacrine-coumarin hybrid compounds on cancer cells is likely to be dependent on the length of the chain between the tacrine and coumarin moieties (1c, 1d = tacrine-(CH2)8–9-coumarin). The most active of the tested compounds, derivatives 1c and 1d, both display longer chains.
Trvalý link: http://hdl.handle.net/11104/0319006