Tacrine derivatives as dual topoisomerase I and II catalytic inhibitors

0446307 - BFÚ 2016 RIV US eng J - Článek v odborném periodiku
Janočková, J. - Plšíková, J. - Koval, J. - Jendželovský, R. - Mikeš, J. - Kašpárková, Jana - Brabec, Viktor - Hamulaková, S. - Fedoročko, P. - Kozurková, M.
Tacrine derivatives as dual topoisomerase I and II catalytic inhibitors.
Bioorganic Chemistry. Roč. 59, APR2015 (2015), s. 168-176. ISSN 0045-2068. E-ISSN 1090-2120
Grant CEP: GA MŠMT(CZ) LD14019
Institucionální podpora: RVO:68081707
Klíčová slova: DNA-BINDING PROPERTIES * CYTOTOXIC ACTIVITY * ANTICANCER DRUGS
Kód oboru RIV: BO - Biofyzika
Impakt faktor: 2.252, rok: 2015

This study examines the binding properties of a series of newly synthetized tacrine derivatives 1-4 and their anticancer effects. Spectroscopic techniques (UV-Vis, fluorescence spectroscopy, thermal denaturation, and linear spectropolarimetry) and viscometry were used to study DNA binding properties and to determine the types of DNA interaction with the studied derivatives. The binding constants for the complexes with DNA were obtained using UV-Vis spectroscopic titrations (K = 1.6 x 10(4)-4.0 x 10(5) M-1) and electrophoretic methods were used to determine the effect of the derivatives on topoisomerase I and II activity. Monotacrine derivative 1 showed evidence of topoisomerase I relaxation activity at a concentration of 30 x 10(-6) M, while bistacrine derivatives 2-4 produced a complete inhibition of topoisomerase I at a concentration of 5 x 10(-6) M. The biological activities of the derivatives were studied using MTT-assay and flow cytometric methods (detection of mitochondrial membrane potential and measurement of cell viability) following incubation of 24 and 48 h with human leukemic cancer cell line HL60.
Trvalý link: http://hdl.handle.net/11104/0248303