Ring-substituted 1-hydroxynaphthalene-2-carboxanilides were previously investigated for their antimycobacterial properties. In our study, we have shown their antiproliferative and cell death-inducing effects in cancer cell lines. Cell proliferation and viability were assessed by WST-1 assay and a dye exclusion test, respectively. Cell cycle distribution, phosphatidylserine externalization, levels of reactive oxygen or nitrogen species (RONS), mitochondrial membrane depolarization, and release of cytochrome c were estimated by flow cytometry. Levels of regulatory proteins were determined by Western blotting. Our data suggest that the ability to inhibit the proliferation of THP-1 or MCF-7 cells might be referred to meta- or para-substituted derivatives with electron-withdrawing groups -F, -Br, or -CF3 at anilide moiety. This effect was accompanied by accumulation of cells in G1 phase. Compound 10 also induced apoptosis in THP-1 cells in association with a loss of mitochondrial membrane potential and production of mitochondrial superoxide. Our study provides a new insight into the action of salicylanilide derivatives, hydroxynaphthalene carboxamides, in cancer cells. Thus, their structure merits further investigation as a model moiety of new small-molecule compounds with potential anticancer properties.
- MeSH
- anilidy chemie farmakologie MeSH
- antitumorózní látky chemie farmakologie MeSH
- apoptóza účinky léků MeSH
- buněčný cyklus účinky léků MeSH
- lidé MeSH
- membránový potenciál mitochondrií účinky léků MeSH
- MFC-7 buňky MeSH
- mitochondrie účinky léků metabolismus MeSH
- molekulární struktura MeSH
- naftoly chemie MeSH
- proliferace buněk účinky léků MeSH
- reaktivní formy kyslíku metabolismus MeSH
- salicylanilidy chemie farmakologie MeSH
- superoxidy metabolismus MeSH
- THP-1 buňky MeSH
- viabilita buněk účinky léků MeSH
- vztahy mezi strukturou a aktivitou MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
A series of twenty-six methoxylated and methylated N-aryl-1-hydroxynaphthalene- 2-carboxanilides was prepared and characterized as potential anti-invasive agents. The molecular structure of N-(2,5-dimethylphenyl)-1-hydroxynaphthalene-2-carboxamide as a model compound was determined by single-crystal X-ray diffraction. All the analysed compounds were tested against the reference strain Staphylococcus aureus and three clinical isolates of methicillin-resistant S.aureus as well as against Mycobacterium tuberculosis and M. kansasii. In addition, the inhibitory profile of photosynthetic electron transport in spinach (Spinacia oleracea L.) chloroplasts was specified. In vitro cytotoxicity of the most effective compounds was tested on the human monocytic leukaemia THP-1 cell line. The activities of N-(3,5-dimethylphenyl)-, N-(3-fluoro-5-methoxy-phenyl)- and N-(3,5-dimethoxyphenyl)-1-hydroxynaphthalene-2-carbox- amide were comparable with or even better than the commonly used standards ampicillin and isoniazid. All promising compounds did not show any cytotoxic effect at the concentration >30 µM. Moreover, an in silico evaluation of clogP features was performed for the entire set of the carboxamides using a range of software lipophilicity predictors, and cross-comparison with the experimentally determined lipophilicity (log k), in consensus lipophilicity estimation, was conducted as well. Principal component analysis was employed to illustrate noticeable variations with respect to the molecular lipophilicity (theoretical/experimental) and rule-of-five violations. Additionally, ligand-oriented studies for the assessment of the three-dimensional quantitative structure-activity relationship profile were carried out with the comparative molecular surface analysis to determine electron and/or steric factors that potentially contribute to the biological activities of the investigated compounds.
- MeSH
- ampicilin farmakologie MeSH
- analýza hlavních komponent MeSH
- anilidy chemická syntéza chemie farmakologie MeSH
- antibakteriální látky chemická syntéza chemie farmakologie MeSH
- chloroplasty účinky léků fyziologie MeSH
- fotosyntéza účinky léků MeSH
- isoniazid farmakologie MeSH
- lidé MeSH
- methicilin rezistentní Staphylococcus aureus účinky léků růst a vývoj MeSH
- metylace MeSH
- mikrobiální testy citlivosti MeSH
- Mycobacterium kansasii účinky léků růst a vývoj MeSH
- Mycobacterium tuberculosis účinky léků růst a vývoj MeSH
- naftoly chemická syntéza chemie farmakologie MeSH
- Spinacia oleracea chemie účinky léků metabolismus MeSH
- THP-1 buňky MeSH
- transport elektronů účinky léků MeSH
- vztahy mezi strukturou a aktivitou MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- srovnávací studie MeSH
A series of 116 small-molecule 1-hydroxynaphthalene-2-carboxanilides was designed based on the fragment-based approach and was synthesized according to the microwave-assisted protocol. The biological activity of all of the compounds was tested on human colon carcinoma cell lines including a deleted TP53 tumor suppressor gene. The mechanism of activity was studied according to the p53 status in the cell. Several compounds revealed a good to excellent activity that was similar to or better than the standard anticancer drugs. Some of these appeared to be more active against the p53 null cells than their wild-type counterparts. Intercalating the properties of these compounds could be responsible for their mechanism of action.
- MeSH
- antitumorózní látky chemická syntéza chemie farmakologie MeSH
- apoptóza účinky léků MeSH
- DNA metabolismus MeSH
- doxorubicin farmakologie MeSH
- HCT116 buňky MeSH
- interkalátory farmakologie MeSH
- knihovny malých molekul chemie farmakologie MeSH
- lidé MeSH
- molekulární modely MeSH
- nádorový supresorový protein p53 metabolismus MeSH
- naftoly chemická syntéza chemie farmakologie MeSH
- proliferace buněk účinky léků MeSH
- racionální návrh léčiv * MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
MiR-34a acts as tumor suppressor microRNA (miRNA) in several cancers, including multiple myeloma (MM), by controlling the expression of target proteins involved in cell cycle, differentiation and apoptosis. Here, we have investigated the combination between miR-34a and γ-secretase inhibitor (γSI), Sirtinol or zoledronic acid (ZOL) in order to enhance the inhibitory action of this miRNA on its canonical targets such as Notch1 and SIRT1, and on Ras/MAPK-dependent pathways. Our data demonstrate that miR-34a synthetic mimics significantly enhance the anti-tumor activity of all the above-mentioned anti-cancer agents in RPMI 8226 MM cells. We found that γSI enhanced miR-34a-dependent anti-tumor effects by activating the extrinsic apoptotic pathway which could overcome the cytoprotective autophagic mechanism. Moreover, the combination between miR-34a and γSI increased the cell surface calreticulin (CRT) expression, that is well known for triggering anti-tumor immunological response. The combination between miR-34a and Sirtinol induced the activation of an intrinsic apoptotic pathway along with increased surface expression of CRT. Regarding ZOL, we found a powerful growth inhibition after enforced miR-34a expression, which was not likely attributable to neither apoptosis nor autophagy modulation. Based on our data, the combination of miR-34a with other anti-cancer agents appears a promising anti-MM strategy deserving further investigation.
- MeSH
- antitumorózní látky terapeutické užití MeSH
- apoptóza účinky léků MeSH
- benzamidy terapeutické užití MeSH
- buněčný cyklus účinky léků MeSH
- kyselina zoledronová terapeutické užití MeSH
- lidé MeSH
- mikro RNA terapeutické užití MeSH
- mnohočetný myelom farmakoterapie MeSH
- nádorové buněčné linie MeSH
- naftoly terapeutické užití MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Series of seventeen new multihalogenated 1-hydroxynaphthalene-2-carboxanilides was prepared and characterized. All the compounds were tested for their activity related to the inhibition of photosynthetic electron transport (PET) in spinach (Spinacia oleracea L.) chloroplasts. 1-Hydroxy-N-phenylnaphthalene-2-carboxamides substituted in the anilide part by 3,5-dichloro-, 4-bromo-3-chloro-, 2,5-dibromo- and 3,4,5-trichloro atoms were the most potent PET inhibitors (IC50 = 5.2, 6.7, 7.6 and 8.0 µM, respectively). The inhibitory activity of these compounds depends on the position and the type of halogen substituents, i.e., on lipophilicity and electronic properties of individual substituents of the anilide part of the molecule. Interactions of the studied compounds with chlorophyll a and aromatic amino acids present in pigment-protein complexes mainly in PS II were documented by fluorescence spectroscopy. The section between P680 and plastoquinone QB in the PET chain occurring on the acceptor side of PS II can be suggested as the site of action of the compounds. The structure-activity relationships are discussed.
- MeSH
- chloroplasty účinky léků metabolismus MeSH
- fotosyntéza účinky léků MeSH
- fotosystém II - proteinový komplex metabolismus MeSH
- inhibiční koncentrace 50 MeSH
- naftoly * chemická syntéza chemie farmakologie MeSH
- Spinacia oleracea účinky léků metabolismus MeSH
- transport elektronů účinky léků MeSH
- Publikační typ
- časopisecké články MeSH
A series of nineteen N-(alkoxyphenyl)-2-hydroxynaphthalene-1-carboxamides and a series of their nineteen positional isomers N-(alkoxyphenyl)-1-hydroxynaphthalene-2-carboxamides were prepared and characterized. Primary in vitro screening of all the synthesized compounds was performed against Mycobacterium tuberculosis H37Ra, M. kansasii and M. smegmatis. Screening of the cytotoxicity of the compounds was performed using human monocytic leukemia THP-1 cells. Some of the tested compounds showed antimycobacterial activity comparable with or higher than that of rifampicin. For example, 2-hydroxy-N-(4-propoxyphenyl)-naphthalene-1-carboxamide showed the highest activity (MIC = 12 µM) against M. tuberculosis with insignificant cytotoxicity. N-[3-(But-2-yloxy)phenyl]- and N-[4-(but-2-yloxy)phenyl]-2-hydroxy-naphthalene-1-carboxamide demonstrated high activity against all tested mycobacterial strains and insignificant cytotoxicity. N-(Alkoxyphenyl)-1-hydroxynaphthalene-2-carboxamides demonstrated rather high effect against M. smegmatis and M. kansasii and strong antiproliferative effect against the human THP-1 cell line. Lipophilicity was found as the main physicochemical parameter influencing the activity. A significant decrease of mycobacterial cell metabolism (viability of M. tuberculosis H37Ra) was observed using MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide) assay. Structure-activity relationships are discussed.
- MeSH
- antibakteriální látky chemická syntéza chemie farmakologie MeSH
- buněčné linie MeSH
- lidé MeSH
- mikrobiální testy citlivosti MeSH
- mikrobiální viabilita účinky léků MeSH
- molekulární struktura MeSH
- Mycobacterium kansasii účinky léků MeSH
- Mycobacterium smegmatis účinky léků MeSH
- Mycobacterium tuberculosis účinky léků MeSH
- naftoly chemická syntéza chemie farmakologie MeSH
- proliferace buněk účinky léků MeSH
- vztahy mezi strukturou a aktivitou MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
Ring-substituted hydroxynaphthanilides are considered as cyclic analogues of salicylanilides, compounds possessing a wide range of pharmacological activities, including promising anticancer properties. The aim of this study was to evaluate the potential anticancer effect of novel nitro-substituted hydroxynaphthanilides with a special focus on structure-activity relationships. The antiproliferative effect was assessed by Water Soluble Tetrazolium Salts-1 (WST-1) assay, and cytotoxicity was evaluated via dye exclusion test. Flow cytometry was used for cell cycle analysis and detection of apoptosis using Annexin V-FITC/PI assay. Protein expression was estimated by Western blotting. Our data indicate that the potential to cause the antiproliferative effect increases with the shift of the nitro substituent from the ortho- to the para-position. The most potent compounds, 3-hydroxy-N-(3-nitrophenyl)naphthalene-2-carboxamide (2), and 2-hydroxy-N-(4-nitrophenyl)-naphthalene-1-carboxamide (6) showed antiproliferative activity against THP-1 and MCF-7 cancer cells without affecting the proliferation of 3T3-L1 non-tumour cells. Compounds 2 and 6 induced the accumulation of THP-1 and MCF-7 cells in G1 phase associated with the downregulation of cyclin E1 protein levels, while the levels of cyclin B1 were not affected. Moreover, compound 2 was found to exert the pro-apoptotic effect on the THP-1 cells. These results suggest that hydroxynaphthanilides might represent a potential model structure for the development of novel anticancer agents.
- MeSH
- anilidy farmakologie MeSH
- antitumorózní látky farmakologie MeSH
- apoptóza účinky léků MeSH
- buněčný cyklus účinky léků MeSH
- lidé MeSH
- MFC-7 buňky MeSH
- molekulární struktura MeSH
- naftaleny chemie farmakologie MeSH
- naftoly farmakologie MeSH
- proliferace buněk účinky léků MeSH
- vztahy mezi strukturou a aktivitou MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
In this study, a series of twenty-two ring-substituted 6-hydroxynaphthalene-2-carboxanilides was prepared and characterized. Primary in vitro screening of the synthesized compounds was performed against Mycobacterium tuberculosis H37Ra, Mycobacterium avium complex and M. avium subsp. paratuberculosis. Derivatives substituted by trifluoromethyl, bromo, methyl and methoxy moieties in C'(3) and C'(4) positions of the anilide ring showed 2-fold higher activity against M. tuberculosis than isoniazid and 4.5-fold higher activity against M. avium subsp. paratuberculosis than rifampicin. 6-Hydroxy-N-(2-methylphenyl)naphthalene-2-carboxamide had MIC=29 μM against M. avium complex. A significant decrease of mycobacterial cell metabolism (viability of M. tuberculosis H37Ra) was observed using MTT assay. Screening of the cytotoxicity of the most effective antimycobacterial compounds was performed using the THP-1 cells, and no significant lethal effect was observed. The structure-activity relationships are discussed.
- MeSH
- anilidy chemická syntéza chemie farmakologie MeSH
- antibakteriální látky chemická syntéza chemie farmakologie MeSH
- lidé MeSH
- mikrobiální testy citlivosti MeSH
- molekulární struktura MeSH
- Mycobacterium cytologie účinky léků MeSH
- nádorové buněčné linie MeSH
- naftoly chemická syntéza chemie farmakologie MeSH
- proliferace buněk účinky léků MeSH
- viabilita buněk účinky léků 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
The presented work describes the development of a simple, fast and effective on-line SPE-UHPLC-UV/vis method using fused core particle columns for extraction, separation and quantitative analysis of the nine illegal dyes, most frequently found in chilli-containing spices. The red dyes Sudan I-IV, Sudan Red 7B, Sudan Red G, Sudan Orange G, Para Red, and Methyl Red were separated and analyzed in less than 9 min without labor-consuming pretreatment procedure. The chromatographic separation was performed on Ascentis Express RP-Amide column with gradient elution using mixture of acetonitrile and water, as a mobile phase at a flow rate of 1.0 mL min(-1) and 55°C of temperature. As SPE sorbent for cleanup and pre-concentration of illegal dyes short guard fused core column Ascentis Express F5 was used. The applicability of proposed method was proven for three different chilli-containing commercial samples. Recoveries for all compounds were between 90% and 108% and relative standard deviation ranged from 1% to 4% for within- and from 2% to 6% for between-day. Limits of detection showed lower values than required by European Union regulations and were in the range of 3.3-10.3 µg L(-1) for standard solutions, 5.6-235.6 µg kg(-1) for chilli-containing spices.
- MeSH
- analýza potravin metody MeSH
- azosloučeniny chemie MeSH
- barvicí látky chemie izolace a purifikace MeSH
- Capsicum chemie MeSH
- extrakce na pevné fázi metody MeSH
- indikátory a reagencie chemie MeSH
- koření analýza MeSH
- naftoly chemie MeSH
- on-line systémy MeSH
- potravinářská barviva chemie MeSH
- vysokoúčinná kapalinová chromatografie metody MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Remote-controlled robotic systems are being used for analysis of various types of analytes in hostile environment including those called extraterrestrial. The aim of our study was to develop a remote-controlled robotic platform (ORPHEUS-HOPE) for bacterial detection. For the platform ORPHEUS-HOPE a 3D printed flow chip was designed and created with a culture chamber with volume 600 μL. The flow rate was optimized to 500 μL/min. The chip was tested primarily for detection of 1-naphthol by differential pulse voltammetry with detection limit (S/N = 3) as 20 nM. Further, the way how to capture bacteria was optimized. To capture bacterial cells (Staphylococcus aureus), maghemite nanoparticles (1 mg/mL) were prepared and modified with collagen, glucose, graphene, gold, hyaluronic acid, and graphene with gold or graphene with glucose (20 mg/mL). The most up to 50% of the bacteria were captured by graphene nanoparticles modified with glucose. The detection limit of the whole assay, which included capturing of bacteria and their detection under remote control operation, was estimated as 30 bacteria per μL.
- MeSH
- alkalická fosfatasa metabolismus MeSH
- design vybavení MeSH
- elektrochemické techniky přístrojové vybavení MeSH
- Escherichia coli enzymologie izolace a purifikace MeSH
- limita detekce MeSH
- magnetické nanočástice chemie MeSH
- mikrobiologie životního prostředí * MeSH
- mikrofluidní analytické techniky přístrojové vybavení MeSH
- naftoly izolace a purifikace MeSH
- robotika přístrojové vybavení MeSH
- Staphylococcus aureus enzymologie izolace a purifikace MeSH
- technologie dálkového snímání přístrojové vybavení MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH