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Trilobolide-steroid hybrids: Synthesis, cytotoxic and antimycobacterial activity
M. Jurášek, P. Džubák, S. Rimpelová, D. Sedlák, P. Konečný, I. Frydrych, S. Gurská, M. Hajdúch, K. Bogdanová, M. Kolář, T. Müller, E. Kmoníčková, T. Ruml, J. Harmatha, PB. Drašar,
Jazyk angličtina Země Spojené státy americké
Typ dokumentu časopisecké články
- MeSH
- androgenní receptory metabolismus MeSH
- antibakteriální látky chemická syntéza chemie farmakologie MeSH
- buňky A549 MeSH
- butyráty chemie MeSH
- Candida účinky léků MeSH
- furany chemie MeSH
- HCT116 buňky MeSH
- lidé MeSH
- molekulární struktura MeSH
- nádorové buněčné linie MeSH
- receptory pro estrogeny metabolismus MeSH
- steroidní receptory metabolismus MeSH
- steroidy chemie MeSH
- syntetická chemie okamžité shody MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
Sesquiterpene lactone trilobolide is a sarco/endoplasmic reticulum Ca(2+)-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 biological 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 10.6μM.
Institute of Experimental Medicine Department of Pharmacology AS CR Prague Czech Republic
Institute of Organic Chemistry and Biochemistry AS CR Prague CZ 166 10 Prague Czech Republic
Citace poskytuje Crossref.org
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