Cholesterol is not only a major component of the cell membrane, but also plays an important role in a wide range of biological processes and pathologies. It is therefore crucial to develop appropriate tools for visualizing intracellular cholesterol transport. Here, we describe new cationic analogues of BODIPY-Cholesterol (TopFluor-Cholesterol, TF-Chol), which combine a positive charge on the sterol side chain and a BODIPY group connected via a C-4 linker. In contrast to TF-Chol, the new analogues TF-1 and TF-3 possessing acetyl groups on the A ring (C-3 position on steroid) internalized much faster and displayed slightly different levels of intracellular localization. Their applicability for cholesterol monitoring was indicated by the fact that they strongly label compartments with accumulated cholesterol in cells carrying a mutation of the Niemann-Pick disease-associated cholesterol transporter, NPC1.
- MeSH
- biologický transport MeSH
- buněčné linie MeSH
- cholesterol analogy a deriváty analýza chemická syntéza metabolismus MeSH
- lidé MeSH
- optické zobrazování MeSH
- sloučeniny boru analýza chemická syntéza chemie metabolismus MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- MeSH
- biopotraviny MeSH
- cholesterol * farmakologie chemická syntéza krev metabolismus normy škodlivé účinky MeSH
- fytosteroly farmakologie terapeutické užití MeSH
- fyziologie výživy MeSH
- HDL-cholesterol * analýza diagnostické užití fyziologie MeSH
- hypercholesterolemie MeSH
- ischemická choroba srdeční MeSH
- jedlá semena MeSH
- kardiovaskulární nemoci dietoterapie prevence a kontrola MeSH
- LDL-cholesterol * analýza diagnostické užití fyziologie škodlivé účinky MeSH
- lidé MeSH
- nenasycené mastné kyseliny MeSH
- oleje rostlin MeSH
- ořechy MeSH
- pohybová aktivita fyziologie MeSH
- rizikové faktory MeSH
- ryby MeSH
- steroly MeSH
- Check Tag
- lidé MeSH
New quaternary ammonium salt-type compounds with lipophilic cholesterol and terpene moieties were synthesized. The compounds showed promising antibacterial and antimycobacterial activities. Those compounds containing the cholesterol moiety showed significant activity against Staphylococcus aureus, Staphylococcus epidermidis, and Enterococcus faecium. On the contrary, the antimycobacterial activity increased with the presence of the terpene unit in the molecule.
- MeSH
- antiinfekční látky chemická syntéza farmakologie MeSH
- cholesterol analogy a deriváty chemická syntéza farmakologie MeSH
- Enterococcus faecium účinky léků růst a vývoj MeSH
- houby účinky léků růst a vývoj MeSH
- kvartérní amoniové sloučeniny chemická syntéza farmakologie MeSH
- mikrobiální testy citlivosti MeSH
- molekulární struktura MeSH
- Mycobacterium účinky léků růst a vývoj MeSH
- racionální návrh léčiv MeSH
- Staphylococcus aureus účinky léků růst a vývoj MeSH
- Staphylococcus epidermidis účinky léků růst a vývoj MeSH
- terpeny diagnostické užití farmakologie MeSH
- vztahy mezi strukturou a aktivitou MeSH
- Publikační typ
- časopisecké články MeSH
- srovnávací studie MeSH
The current interest of the team has been focused on investigation of novel amides with potential cytotoxicity. The presented series of compounds was synthesized from selected steryl hemiesters and heteroaromatic amines. The synthetic protocol was designed in a simple and economic way, and divided into several general methodologies applicable to the compounds synthesized. The cytotoxicity was tested on cells derived from human T-lymphoblastic leukemia, breast adenocarcinoma and cervical cancer, and compared with tests on normal human fibroblasts. Most of the lanosterol-based compounds (3-5 and 7-10) showed medium to good cytotoxicity, while only two derivatives of cholesterol (18 and 19) showed medium cytotoxicity on human T-lymphoblastic leukemia cell line. The compounds 8 and 9 displayed the reasonable cytotoxicity among this series of amides, tested on the cell lines of T-lymphoblastic leukemia [14.5±0.4 μM (8) and 18.5±3.9 μM (9)], breast adenocarcinoma [19.5±2.1 μM (8) and 23.1±4.0 μM (9)] and cervical cancer [24.8±5.3 μM (8) and 29.1±4.7 μM (9)]. Only the compound 8 was adequately less active on normal human fibroblasts (40.4±11.1 μM).
- MeSH
- amidy chemie MeSH
- aminy chemie MeSH
- antitumorózní látky chemická syntéza farmakologie MeSH
- cholesterol analogy a deriváty chemická syntéza farmakologie MeSH
- cytotoxiny chemická syntéza farmakologie MeSH
- fibroblasty cytologie účinky léků metabolismus MeSH
- lanosterol analogy a deriváty chemická syntéza farmakologie MeSH
- léky antitumorózní - screeningové testy MeSH
- lidé MeSH
- magnetická rezonanční spektroskopie MeSH
- nádorové buněčné linie MeSH
- proliferace buněk účinky léků MeSH
- viabilita buněk účinky léků MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
New type of linear cholesterol-like molecules based on cholesterol extended by attachment of etienic acid derivatives was designed and oligosteroids with two to four units were synthesized. Amide bond was used for inter steroid connections and 1-hydroxybenzotriazole active ester method was adapted for their formations. Use of disteroids as larger building blocks was applied.
