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  1. Article ; Online: Tacrine-Coumarin Derivatives as Topoisomerase Inhibitors with Antitumor Effects on A549 Human Lung Carcinoma Cancer Cell Lines

    Eva Konkoľová / Monika Hudáčová / Slávka Hamuľaková / Rastislav Jendželovský / Jana Vargová / Juraj Ševc / Peter Fedoročko / Mária Kožurková

    Molecules, Vol 26, Iss 4, p

    2021  Volume 1133

    Abstract: 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 ... ...

    Abstract 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 ( h TOPI) 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-(CH 2 ) 8–9 -coumarin). The most active of the tested compounds, derivatives 1c and 1d , both display longer chains.
    Keywords tacrine-coumarin derivatives ; DNA ; topoisomerases I ; II ; cytotoxicity ; lung carcinoma cells ; A549 ; Organic chemistry ; QD241-441
    Subject code 540
    Language English
    Publishing date 2021-02-01T00:00:00Z
    Publisher MDPI AG
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  2. Article ; Online: Synthesis of New Biscoumarin Derivatives, In Vitro Cholinesterase Inhibition, Molecular Modelling and Antiproliferative Effect in A549 Human Lung Carcinoma Cells

    Monika Hudáčová / Slávka Hamuľaková / Eva Konkoľová / Rastislav Jendželovský / Jana Vargová / Juraj Ševc / Peter Fedoročko / Ondrej Soukup / Jana Janočková / Veronika Ihnatova / Tomáš Kučera / Petr Bzonek / Nikola Novakova / Daniel Jun / Lucie Junova / Jan Korábečný / Kamil Kuča / Mária Kožurková

    International Journal of Molecular Sciences, Vol 22, Iss 3830, p

    2021  Volume 3830

    Abstract: A series of novel C4-C7-tethered biscoumarin derivatives ( 12a – e ) linked through piperazine moiety was designed, synthesized, and evaluated biological/therapeutic potential. Biscoumarin 12d was found to be the most effective inhibitor of both ... ...

    Abstract A series of novel C4-C7-tethered biscoumarin derivatives ( 12a – e ) linked through piperazine moiety was designed, synthesized, and evaluated biological/therapeutic potential. Biscoumarin 12d was found to be the most effective inhibitor of both acetylcholinesterase (AChE, IC 50 = 6.30 µM) and butyrylcholinesterase (BChE, IC 50 = 49 µM). Detailed molecular modelling studies compared the accommodation of ensaculin (well-established coumarin derivative tested in phase I of clinical trials) and 12d in the human recombinant AChE ( h AChE) active site. The ability of novel compounds to cross the blood–brain barrier (BBB) was predicted with a positive outcome for compound 12e . The antiproliferative effects of newly synthesized biscoumarin derivatives were tested in vitro on human lung carcinoma cell line (A549) and normal colon fibroblast cell line (CCD-18Co). The effect of derivatives on cell proliferation was evaluated by MTT assay, quantification of cell numbers and viability, colony-forming assay, analysis of cell cycle distribution and mitotic activity. Intracellular localization of used derivatives in A549 cells was confirmed by confocal microscopy. Derivatives 12d and 12e showed significant antiproliferative activity in A549 cancer cells without a significant effect on normal CCD-18Co cells. The inhibition of h AChE/human recombinant BChE ( h BChE), the antiproliferative activity on cancer cells, and the ability to cross the BBB suggest the high potential of biscoumarin derivatives. Beside the treatment of cancer, 12e might be applicable against disorders such as schizophrenia, and 12d could serve future development as therapeutic agents in the prevention and/or treatment of Alzheimer’s disease.
    Keywords biscoumarin ; Alzheimer’s disease ; blood–brain barrier ; cholinesterase ; antiproliferative activity ; A549 ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
    Subject code 610
    Language English
    Publishing date 2021-04-01T00:00:00Z
    Publisher MDPI AG
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

    Full text online

    More links

    Kategorien

    Inter-library loan at ZB MED

    Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

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