Nanoparticles can be considered as a useful tool for improving properties of poorly soluble active ingredients. Hydrochlorothiazide (Class IV of the Biopharmaceutical Classification System) was chosen as a model compound. Antisolvent precipitation-solvent evaporation and emulsion solvent evaporation methods were used for preparation of 18 samples containing hydrochlorothiazide nanoparticles. Water solutions of surfactants sodium dodecyl sulfate, Tween 80 and carboxymethyl dextran were used in mass concentrations of 1%, 3% and 5%. Acetone and dichloromethane were used as solvents of the model compound. The particle size of the prepared samples was measured by dynamic light scattering. The selected sample of hydrochlorothiazide nanoparticles stabilized with carboxymethyl dextran sodium salt with particle size 2.6 nm was characterized additionally by Fourier transform mid-infrared spectroscopy and scanning electron microscopy. It was found that the solubility of this sample was 6.5-fold higher than that of bulk hydrochlorothiazide.
Ring-substituted 8-hydroxyquinoline-2-carboxanilides inhibited photosynthetic electron transport (PET) through photosystem (PS) II. Their inhibitory efficiency depended on the compound lipophilicity, the electronic properties of the substituent R and the position of the substituent R on the benzene ring. The most effective inhibitors showing IC50 values in the range 2.3-3.6μM were substituted in C'(3) by F, CH3, Cl and Br. The dependence of the PET-inhibiting activity on the lipophilicity of the compounds was quasi-parabolic for 3-substituted derivatives, while for C'(2) ones a slight increase and for C'(4) derivatives a sharp decrease of the activity were observed with increasing lipophilicity. In addition, the dependence of PET-inhibiting activity on electronic Hammett's σ parameter of the substituent R was observed with optimum σ value 0.06 for C'(4) and 0.34 for C'(3) substituted derivatives, while the value of σ parameter did not significantly influence the PET-inhibiting activity of C'(2) substituted compounds. Interactions of the studied compounds with chlorophyll a and aromatic amino acids present in the pigment-protein complexes mainly in PS II were documented by fluorescence spectroscopy. The section between P680 and plastoquinone QB occurring on the acceptor side of PS II can be suggested as the site of action of the compounds.
- MeSH
- anilidy chemická syntéza chemie metabolismus MeSH
- chlorofyl chemie MeSH
- chloroplasty metabolismus MeSH
- fluorescenční spektrometrie MeSH
- fotosyntéza MeSH
- fotosystém II - proteinový komplex antagonisté a inhibitory metabolismus MeSH
- oxychinolin chemie MeSH
- Spinacia oleracea metabolismus MeSH
- transport elektronů MeSH
- vazba proteinů MeSH
- vztahy mezi strukturou a aktivitou MeSH
- Publikační typ
- časopisecké články MeSH
In this study, a series of twenty-two ring-substituted 8-hydroxyquinoline-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. Some of the tested compounds showed the antimycobacterial activity against M. avium subsp. paratuberculosis comparable with or higher than that of rifampicin. 8-Hydroxy-N-[3-(trifluoromethyl)phenyl]- and 8-hydroxy-N-[4-(trifluoromethyl)phenyl]quinoline-2-carboxamide showed MIC=24 μM against all tested mycobacterial strains. 3-Methoxyphenyl- and 3-methylphenyl derivatives expressed MIC=27 or 29 μM also against all the tested strains. Their activity against M. avium subsp. paratuberculosis was 4-fold higher than that of rifampicin. 2-Bromophenyl- and 2-(trifluoromethyl)phenyl derivatives had MIC=23 or 24 μM against M. tuberculosis. A significant decrease of mycobacterial cell metabolism (viability of M. tuberculosis H37Ra) was observed using MTT assay. Screening of cytotoxicity of the compounds was performed using the THP-1 cells, and no significant lethal effect was observed up to tested concentration 30 μM. The structure-activity relationships are discussed.
- MeSH
- antibakteriální látky chemie farmakologie MeSH
- buněčné linie MeSH
- lidé MeSH
- mikrobiální testy citlivosti MeSH
- Mycobacterium avium účinky léků MeSH
- Mycobacterium tuberculosis účinky léků metabolismus MeSH
- oxychinolin chemie MeSH
- preklinické hodnocení léčiv metody MeSH
- testy toxicity MeSH
- vztahy mezi strukturou a aktivitou * MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem 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
Inhibition of photosynthetic electron transport (PET) in spinach chloroplasts by sixty-one ring-substituted N-benzylsalicylamides was investigated. The inhibitory potency of the compounds expressed by IC50 value varied from 2.0 to 425.3 μmol/L. Several evaluated compounds can be considered as effective PET inhibitors; these include N-(3,4- dichlorobenzyl)-2-hydroxy-5-nitrobenzamide (IC50 = 2.0 μmol/L), 3,5-dibromo-N-(3,4-dichlorobenzyl)-2-hydroxybenzamide (IC50 = 2.3 μmol/L) and 3,5-dibromo-N-(4-chlorobenzyl)-2-hydroxybenzamide (IC50 = 2.6 μmol/L) with activity comparable with that of the standard Diuron (IC50 = 1.9 μmol/L). The PET inhibiting activity increased approximately linearly with increasing lipophilicity of the compounds as well as with the increasing sum of Hammett σ constants of the substituents on the acyl fragment (R(1) = H, 5-OCH3, 5-CH3, 5-Cl, 5-Br, 5-NO2, 4-OCH3, 4-Cl, 3,5-Cl and 3,5-Br) and the benzylamide fragment (R(2) = H, 4-OCH3, 4-CH3, 4-F, 4-Cl and 3,4-Cl). Based on the evaluated structure-PET inhibiting activity relationships (QSAR) it was confirmed that the inhibitory activity of the compounds depends on lipophilicity (log P or distributive parameters π; (1) and π(2)of individual substituents) and electronic properties of the substituents on the acyl (σ(1)) and the benzylamide fragments (σ(2)), the contribution of σ(1) being more significant than that of σ(2).
- MeSH
- chemické modely MeSH
- chloroplasty účinky léků metabolismus MeSH
- fotosyntéza účinky léků MeSH
- kvantitativní vztahy mezi strukturou a aktivitou MeSH
- molekulární struktura MeSH
- racionální návrh léčiv MeSH
- salicylamidy chemická syntéza chemie farmakologie MeSH
- Spinacia oleracea účinky léků metabolismus MeSH
- transport elektronů účinky léků MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Naphthoquinones represent the group of plant secondary metabolites with cytotoxic properties based on their ability to generate reactive oxygen species and interfere with the processes of cell respiration. Due to this fact, the possible cytotoxic mechanisms on cellular and subcellular levels are investigated intensively. There are many targets of cytotoxic action on the cellular level; however, DNA is a critical target of many cytotoxic compounds. Due to the cytotoxic properties of naphthoquinones, it is necessary to study the processes of naphthoquinones, DNA interactions (1,4-naphthoquinone, binapthoquinone, juglone, lawsone, plumbagin), especially by using modern analytical techniques. In our work, the Raman spectroscopy was used to determine the possible binding sites of the naphthoquinones on the DNA and to characterize the bond of naphthoquinone to DNA. Experimental data reveals the relationships between the perturbations of structure-sensitive Raman bands and the types of the naphthoquinones involved. The modification of DNA by the studied naphthoquinones leads to the nonspecific interaction, which causes the transition of B-DNA into A-DNA conformation. The change of the B-conformation of DNA for all measured DNA modified by naphthoquinones except plumbagin is obvious.
- MeSH
- B-DNA chemie metabolismus MeSH
- DNA chemie metabolismus MeSH
- naftochinony chemie metabolismus MeSH
- Ramanova spektroskopie MeSH
- reaktivní formy kyslíku metabolismus MeSH
- rostliny chemie metabolismus MeSH
- sekundární metabolismus * MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
A series of twenty substituted 2-hydroxy-3-[(2-aryloxyethyl)amino]propyl 4-[(alkoxycarbonyl)amino]benzoates were prepared and characterized. As similar compounds have been described as potential antimycobacterials, primary in vitro screening of the synthesized carbamates was also performed against two mycobacterial species. 2-Hydroxy-3-[2-(2,6-dimethoxyphenoxy)ethylamino]-propyl 4-(butoxycarbonylamino)benzoate hydrochloride, 2-hydroxy-3-[2-(4-methoxyphenoxy)ethylamino]-propyl 4-(butoxycarbonylamino)benzoate hydrochloride, and 2-hydroxy-3-[2-(2-methoxyphenoxy)ethylamino]-propyl 4-(butoxycarbonylamino)benzoate hydrochloride showed higher activity against M. avium subsp. paratuberculosis and M. intracellulare than the standards ciprofloxacin, isoniazid, or pyrazinamide. Cytotoxicity assay of effective compounds was performed using the human monocytic leukaemia THP-1 cell line. Compounds with predicted amphiphilic properties were also tested for their effects on the rate of photosynthetic electron transport (PET) in spinach (Spinacia oleracea L.) chloroplasts. All butyl derivatives significantly stimulated the rate of PET, indicating that the compounds can induce conformational changes in thylakoid membranes resulting in an increase of their permeability and so causing uncoupling of phosphorylation from electron transport.
- MeSH
- antibakteriální látky chemická syntéza farmakologie MeSH
- benzoáty chemická syntéza farmakologie MeSH
- karbamáty chemická syntéza farmakologie MeSH
- Mycobacterium avium subsp. paratuberculosis účinky léků MeSH
- rozpřahující látky chemická syntéza farmakologie MeSH
- Spinacia oleracea účinky léků MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
In this study, a series of 22 ring-substituted 1-hydroxynaphthalene-2-carboxanilides were prepared and characterized. Primary in vitro screening of the synthesized compounds was performed against Mycobacterium marinum, Mycobacterium kansasii and Mycobacterium smegmatis. The compounds were also tested for their activity related to inhibition of photosynthetic electron transport (PET) in spinach (Spinacia oleracea L.) chloroplasts. Most of tested compounds showed the antimycobacterial activity against the three strains comparable or higher than the standard isoniazid. N-(3-Fluorophenyl)-1-hydroxynaphthalene-2-carboxamide showed the highest biological activity (MIC=28.4μmol/L) against M. marinum, N-(4-fluorophenyl)-1-hydroxynaphthalene-2-carboxamide showed the highest biological activity (MIC=14.2μmol/L) against M. kansasii, and N-(4-bromophenyl)-1-hydroxynaphthalene-2-carboxamide expressed the highest biological activity (MIC=46.7μmol/L) against M. smegmatis. This compound and 1-hydroxy-N-(3-methylphenyl)naphthalene-2-carboxamide were the most active compounds against all three tested strains. The PET inhibition expressed by IC50 value of the most active compound 1-hydroxy-N-(3-trifluoromethylphenyl)naphthalene-2-carboxamide was 5.3μmol/L. The most effective compounds demonstrated insignificant toxicity against the human monocytic leukemia THP-1 cell line. For all compounds, structure-activity relationships are discussed.
- MeSH
- anilidy chemická syntéza chemie farmakologie MeSH
- antibakteriální látky chemická syntéza chemie farmakologie MeSH
- chloroplasty účinky léků metabolismus MeSH
- fotosyntéza účinky léků MeSH
- herbicidy chemická syntéza chemie toxicita MeSH
- lidé MeSH
- mikrobiální testy citlivosti MeSH
- Mycobacterium účinky léků MeSH
- nádorové buněčné linie MeSH
- naftaleny chemie MeSH
- Spinacia oleracea metabolismus MeSH
- transport elektronů účinky léků MeSH
- viabilita buněk účinky léků MeSH
- vztahy mezi strukturou a aktivitou MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Publikační typ
- abstrakt z konference MeSH
In this study, a series of N-substituted 2-aminobenzothiazoles was prepared according to a recently developed method. Twelve compounds were tested for their activity related to the inhibition of photosynthetic electron transport (PET) in spinach (Spinacia oleracea L.) chloroplasts. Primary in vitro screening of the discussed compounds was also performed against fungal, bacterial and mycobacterial species. The biological activities of some compounds were comparable or higher than the standards phenoxymethylpenicillin or pyrazinamide. The most effective compounds demonstrated insignificant toxicity against the human monocytic leukemia THP-1 cell line. For all compounds, the structure-activity relationships are discussed.
- MeSH
- antifungální látky metabolismus farmakologie MeSH
- antiinfekční látky chemická syntéza chemie farmakologie MeSH
- antitumorózní látky chemická syntéza chemie farmakologie MeSH
- benzothiazoly chemická syntéza chemie farmakologie MeSH
- chloroplasty účinky léků MeSH
- herbicidy chemická syntéza chemie farmakologie MeSH
- léky antitumorózní - screeningové testy MeSH
- lidé MeSH
- mikrobiální testy citlivosti MeSH
- nádorové buněčné linie MeSH
- Spinacia oleracea MeSH
- vztahy mezi strukturou a aktivitou MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
