Three BS-BODIPY (brassinosteroids-4,4-difluoro-4-bora-3a,4a-diaza-s-indacene) conjugates were synthesized and their fluorescent and immunological properties were investigated. Two of the conjugates, having present all the functional groups characteristic of BS, were shown to be potentially useful as biological probes to study involvement of BS into physiological processes in living cells.

• MeSH
• brassinosteroidy chemie   MeSH
• sloučeniny boru chemie   MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

meso-Methyl BODIPY photocages stand out for their absorption properties and easy chromophore derivatization. However, their low uncaging efficiencies often hinder applications requiring release of protected substrates in high amounts. In this study, we demonstrate that the sulfonothioated BODIPY group photocleaves a sulfonylthio group from the meso-methyl position with a 10-fold higher quantum yield than the most efficient leaving groups studied to date. Photocleavage, observed in solution and in cells, is accompanied by the spatiotemporally controlled photorelease of H2Sn. For this reason, sulfonothioated BODIPY may be applied in cell signaling, redox homeostasis, and metabolic regulation studies.

• MeSH
• signální transdukce * MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Brassinosteroids (BRs) are plant hormones of steroid nature, regulating various developmental and adaptive processes. The perception, transport, and signaling of BRs are actively studied nowadays via a wide range of biochemical and genetic tools. However, most of the knowledge about BRs intracellular localization and turnover relies on the visualization of the receptors or cellular compartments using dyes or fluorescent protein fusions. We have previously synthesized a conjugate of epibrassinolide with green fluorescent dye BODIPY (eBL-BODIPY). Here we present a detailed assessment of the compound bioactivity and its suitability as probe for in vivo visualization of BRs. We show that eBL-BODIPY rapidly penetrates epidermal cells of Arabidopsis thaliana roots and after long exposure causes physiological and transcriptomic responses similar to the natural hormone.

• MeSH
• Arabidopsis metabolismus   MeSH
• brassinosteroidy chemie   metabolismus   MeSH
• fluorescenční barviva chemie   MeSH
• kořeny rostlin metabolismus   MeSH
• regulátory růstu rostlin metabolismus   MeSH
• signální transdukce MeSH
• sloučeniny boru chemie   MeSH
• steroidy heterocyklické chemie   MeSH
• Publikační typ
• časopisecké články MeSH

Photodynamic therapy (PDT) is a clinically-approved cancer treatment that is based on production of cytotoxic reactive oxygen species to induce cell death. However, its efficiency depends on distribution of photosensitizer (PS) and depth of light penetration through the tissues. Tendency of pathological cancer tissues to exhibit lower pH than healthy tissues inspired us to explore dual-targeted pH-activatable photosensitizers based on tunable near-infrared (NIR) boron-dipyrromethene (BODIPY) dyes. Our BODIPY PSs were designed to carry three main attributes: (i) biotin or cRGD peptide as an effective cancer cell targeting unit, (ii) amino moiety that is protonated in acidic (pH <6.5) conditions for pH-activation of the PS based on photoinduced electron transfer (PET) and (iii) hydrophilic groups enhancing the water solubility of very hydrophobic BODIPY dyes. Illumination of such compounds with suitable light (>640nm) allowed for high phototoxicity against HeLa (αvβ3 integrin and biotin receptor positive) and A549 (biotin receptor positive) cells compared to healthy MRC-5 (biotin negative) cells. Moreover, no dark toxicity was observed on selected cell lines (>10 μM) providing promising photosensitizers for tumour-targeted photodynamic therapy.

• MeSH
• biotin * chemie   MeSH
• buňky A549 MeSH
• cyklické peptidy chemie   farmakologie   MeSH
• fotochemoterapie * MeSH
• fotosenzibilizující látky * chemie   farmakologie   MeSH
• HeLa buňky MeSH
• infračervené záření MeSH
• koncentrace vodíkových iontů MeSH
• lidé MeSH
• sloučeniny boru * chemie   farmakologie   MeSH
• viabilita buněk účinky léků   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

Three monosubstituted 3-phenylselanyl and 3-phenyltellanyl BODIPY derivatives were synthesized and their spectroscopic properties were characterized and compared to those of iodine and chlorine-atoms containing analogues as well as an unsubstituted BODIPY derivative. The fluorescence quantum yields were found to decrease, whereas the intersystem crossing quantum yields (ΦISC), determined by transient spectroscopy, increased in the order of the H → Cl → Se/I → Te substitution. The maximum ΦISC, found for the 3-phenyltellanyl derivative, was 59%. The results are interpreted in terms of the internal heavy-atom effect of the substituents.

• MeSH
• benzenové deriváty chemie   MeSH
• fluorescenční barviva chemie   MeSH
• fluorescenční spektrometrie MeSH
• organoselenové sloučeniny chemie   MeSH
• sloučeniny boru chemie   MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Breast cancer resistance protein (BCRP) and P-glycoprotein (P-gp) are the most abundantly expressed ATP-binding cassette (ABC) drug transporters in the placenta. They recognize a large, partly overlapping spectrum of chemically unrelated compounds and affect their transplacental passage. In this study we investigate the effect of Bcrp and P-gp on the transplacental pharmacokinetics of their specific and common substrates employing the technique of dually perfused rat placenta. We show that the clearance of rhodamine 123 (P-gp substrate), glyburide (BCRP substrate) and BODIPY FL prazosin (P-gp and BCRP substrate) in fetal-to-maternal direction is 11, 11.2 and 4 times higher, respectively, than that in the maternal-to-fetal direction. In addition, all of these substances were found to be transported from the fetal compartment even against concentration gradient. We thus demonstrate the ability of placental ABC transporters to hinder maternal-to-fetal and accelerate fetal-to-maternal transport in a concentration-dependent manner. However, by means of pharmacokinetic modeling we describe the inverse correlation between lipid solubility of a molecule and its active transport by placental ABC efflux transporters. Therefore, in the case of highly lipophilic substrates, such as BODIPY FL prazosin in this study, the efficacy of efflux transporters to pump the molecule back to the maternal circulation is markedly limited.

• MeSH
• ABC transportéry metabolismus   MeSH
• biologický transport MeSH
• glibenklamid farmakokinetika   chemie   MeSH
• krysa rodu rattus MeSH
• lipidy chemie   MeSH
• maternofetální výměna látek MeSH
• P-glykoprotein metabolismus   MeSH
• perfuze MeSH
• placenta metabolismus   MeSH
• prazosin analogy a deriváty   farmakokinetika   chemie   MeSH
• rhodamin 123 farmakokinetika   chemie   MeSH
• rozpustnost MeSH
• sloučeniny boru farmakokinetika   chemie   MeSH
• substrátová specifita MeSH
• techniky in vitro MeSH
• těhotenství MeSH
• vztah mezi dávkou a účinkem léčiva MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• těhotenství MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• práce podpořená grantem MeSH

Betulinic acid (BA) is a potent triterpene, which has shown promising potential in cancer and HIV-1 treatment. Here, we report a synthesis and biological evaluation of 17 new compounds, including BODIPY labelled analogues derived from BA. The analogues terminated by amino moiety showed increased cytotoxicity (e.g., BA had on CCRF-CEM IC50 > 50 μM, amine 3 IC50 0.21 and amine 14 IC50 0.29). The cell-cycle arrest was evaluated and did not show general features for all the tested compounds. A fluorescence microscopy study of six derivatives revealed that only 4 and 6 were detected in living cells. These compounds were colocalized with the endoplasmic reticulum and mitochondria, indicating possible targets in these organelles. The study of anti-HIV-1 activity showed that 8, 10, 16, 17 and 18 have had IC50i > 10 μM. Only completely processed p24 CA was identified in the viruses formed in the presence of compounds 4 and 12. In the cases of 2, 8, 9, 10, 16, 17 and 18, we identified not fully processed p24 CA and p25 CA-SP1 protein. This observation suggests a similar mechanism of inhibition as described for bevirimat.

• Publikační typ
• časopisecké články MeSH

Here, we report synthesis and biological evaluation of fluorescent nandrolone-3-carboxymethyloxime derivatives conjugated with green-emitting bodipy dye via PEG linkers. All the newly-synthesized compounds were evaluated for their effect on cell proliferation in vitro in MCF-7, LNCaP, PC-3 and HEK 293T model cell lines using WST-1 assay. By means of live-cell fluorescence microscopy, the intracellular localization of nandrolone-bodipy conjugates was revealed in endoplasmic reticulum. Moreover, we performed competitive localization study with nonfluorescent nandrolone, metandrolone, boldenone, trenbolone, and testosterone.

• MeSH
• fluorescenční barviva chemická syntéza   chemie   MeSH
• fluorescenční mikroskopie MeSH
• HEK293 buňky MeSH
• HeLa buňky MeSH
• lidé MeSH
• MFC-7 buňky MeSH
• molekulární konformace MeSH
• nádorové buněčné linie MeSH
• nandrolon chemie   farmakologie   MeSH
• proliferace buněk účinky léků   MeSH
• sloučeniny boru chemie   farmakologie   MeSH
• vztah mezi dávkou a účinkem léčiva MeSH
• vztahy mezi strukturou a aktivitou MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

New fluorescent nucleosides and nucleoside triphosphate (dNTPs) analogs bearing the F-Bodipy fluorophore linked through a short, flexible nonconjugate tether were synthesized. The Bodipy-labeled dNTPs were substrates for several DNA polymerases which incorporated them into DNA in primer extension, nicking enzyme amplification reaction, and polymerase chain reaction. The fluorescence of F-Bodipy is not quenched upon incorporation in DNA and can be detected both in solutions and on gels.

• MeSH
• DNA-dependentní DNA-polymerasy metabolismus   MeSH
• DNA chemická syntéza   chemie   genetika   MeSH
• fluorescenční barviva chemie   MeSH
• nukleotidy chemie   MeSH
• polyfosfáty chemie   MeSH
• sekvence nukleotidů MeSH
• sloučeniny boru chemie   MeSH
• techniky syntetické chemie MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Synthesis of cytosine, uracil, and 7-deazaadenine 2'-deoxyribonucleosides and triphosphates (dNTPs) bearing hexamethylated phenyl-bodipy fluorophore attached at position 5 of pyrimidines or at position 7 of 7-deazapurine was developed. All the title labeled nucleosides and dNTPs displayed bright green fluorescence with very high quantum yields. The modified dNmBdpTPs were good substrates to diverse DNA polymerases and were used for in vitro enzymatic synthesis of labeled DNA by primer extension or PCR. In combination with cationic cyclodextrin-peptide-based dNTP transporter, the dNmBdpTPs were successfully used for staining of genomic DNA in living cells for applications in confocal microscopy and in flow cytometry. The best performing cytosine nucleotide dCmBdpTP was used to monitor mitosis in live cells.

• MeSH
• adenin analogy a deriváty   chemie   MeSH
• barvení a značení MeSH
• cytosin chemie   MeSH
• deoxyribonukleosidy chemie   MeSH
• DNA analýza   MeSH
• fluorescenční barviva chemie   MeSH
• lidé MeSH
• metylace MeSH
• nádorové buněčné linie MeSH
• optické zobrazování MeSH
• polyfosfáty chemie   MeSH
• průtoková cytometrie MeSH
• puriny chemie   MeSH
• sloučeniny boru chemie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH