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.

• MeSH
• buňky A549 MeSH
• DNA-topoisomerasy I metabolismus   MeSH
• DNA-topoisomerasy typu II metabolismus   MeSH
• inhibitory topoisomerasy I chemie   farmakologie   MeSH
• inhibitory topoisomerasy II chemie   farmakologie   MeSH
• kumariny chemie   farmakologie   MeSH
• lidé MeSH
• molekulární struktura MeSH
• nádorové buňky kultivované MeSH
• proliferace buněk účinky léků   MeSH
• proteiny vázající poly-ADP-ribosu antagonisté a inhibitory   metabolismus   MeSH
• protinádorové látky chemie   farmakologie   MeSH
• screeningové testy protinádorových léčiv MeSH
• takrin chemie   farmakologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

The interactions of epoxiconazole and prothioconazole with human serum albumin and bovine serum albumin were investigated using spectroscopic methods complemented with molecular modeling. Spectroscopic techniques showed the formation of pesticide/serum albumin complexes with the static type as the dominant mechanism. The association constants ranged from 3.80 × 104-6.45 × 105 L/mol depending on the pesticide molecule (epoxiconazole, prothioconazole) and albumin type (human or bovine serum albumin). The calculated thermodynamic parameters revealed that the binding of pesticides into serum albumin macromolecules mainly depended on hydrogen bonds and van der Waals interactions. Synchronous fluorescence spectroscopy and the competitive experiments method showed that pesticides bind to subdomain IIA, near tryptophan; in the case of bovine serum albumin also on the macromolecule surface. Concerning prothioconazole, we observed the existence of an additional binding site at the junction of domains I and III of serum albumin macromolecules. These observations were corroborated well by molecular modeling predictions. The conformation changes in secondary structure were characterized by circular dichroism, three-dimensional fluorescence, and UV/VIS absorption methods.

• MeSH
• cirkulární dichroismus metody   MeSH
• epoxidové sloučeniny chemie   MeSH
• fluorescenční spektrometrie metody   MeSH
• hydrofobní a hydrofilní interakce MeSH
• lidé MeSH
• lidský sérový albumin chemie   MeSH
• pesticidy chemie   MeSH
• sekundární struktura proteinů MeSH
• sérový albumin hovězí chemie   MeSH
• simulace molekulového dockingu metody   MeSH
• skot MeSH
• statická elektřina MeSH
• teplota MeSH
• triazoly chemie   MeSH
• vazba proteinů MeSH
• vazebná místa MeSH
• vodíková vazba MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• skot MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH