Number of the records: 1  

Trilobolide-steroid hybrids: Synthesis, cytotoxic and antimycobacterial activity

  1. 1.
    SYSNO ASEP0473082
    Document TypeJ - Journal Article
    R&D Document TypeJournal Article
    Subsidiary JČlánek ve WOS
    TitleTrilobolide-steroid hybrids: Synthesis, cytotoxic and antimycobacterial activity
    Author(s) Jurášek, M. (CZ)
    Džubák, P. (CZ)
    Rimpelová, S. (CZ)
    Sedlák, David (UMG-J) RID
    Konečný, P. (CZ)
    Frydrych, I. (CZ)
    Gurska, S. (CZ)
    Hajdúch, M. (CZ)
    Bogdanová, K. (CZ)
    Kolář, M. (CZ)
    Muller, Tomáš (UMG-J)
    Kmoníčková, Eva (UEM-P) RID
    Ruml, T. (CZ)
    Harmatha, Juraj (UOCHB-X) RID, ORCID
    Drašar, P. B. (CZ)
    Number of authors15
    Source TitleSteroids. - : Elsevier - ISSN 0039-128X
    Roč. 117, JAN (2017), s. 97-104
    Number of pages8 s.
    Languageeng - English
    CountryUS - United States
    KeywordsTrilobolide ; Steroids ; Click chemistry ; Cytotoxicity ; sar ; Steroid receptor
    Subject RIVEB - Genetics ; Molecular Biology
    OECD categoryBiochemistry and molecular biology
    Subject RIV - cooperationInstitute of Organic Chemistry and Biochemistry - Organic Chemistry
    R&D ProjectsLO1304 GA MŠMT - Ministry of Education, Youth and Sports (MEYS)
    LO1220 GA MŠMT - Ministry of Education, Youth and Sports (MEYS)
    LM2015063 GA MŠMT - Ministry of Education, Youth and Sports (MEYS)
    Institutional supportUMG-J - RVO:68378050 ; UEM-P - RVO:68378041 ; UOCHB-X - RVO:61388963
    UT WOS000392566800014
    DOI https://doi.org/10.1016/j.steroids.2016.08.011
    AnnotationSesquiterpene lactone trilobolide is a sarco/endoplasmic reticulum Ca2+-ATPase (SERCA) inhibitor, thus depleting the Ins(1,4,5)P3-sensitive intracellular calcium stores. Here, we describe a synthesis of a series of 6 trilobolide-steroids conjugates (estradiol, pregnene, dehydroepiandrosterone, and testosterone). We found that the newly synthesized Tb-based compounds possess different remarkable biologital activities. Cancer cell cytotoxicity and preferential selectivity is represented in our study by a Tb-pregnene derivative. The most cytotoxic clickates of estradiol and pregnene were studied by FACS where impact on cell cycle and RNA synthesis was observed; live-cell microscopy revealed the impact on cell organelle morphology particularly endoplasmic reticulum, mitochondria and nucleus. Further, we have studied the estrogenic and androgenic properties of the cliCkate molecules using cell-based luciferase assays. Finally, antimycobacterial tests revealed that testosterone and estradiol derivatives potentiated the antimycobacterial activity up to IC50 of 10.6 mu M. (C) 2016 Elsevier Inc. All rights reserved.
    WorkplaceInstitute of Molecular Genetics
    ContactNikol Škňouřilová, nikol.sknourilova@img.cas.cz, Tel.: 241 063 217
    Year of Publishing2017
Number of the records: 1  

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