Showing papers by "Josef Jampilek published in 2015"
TL;DR: A comprehensive up-to-date review related to the preparation and the biological activity of nanoformulations enabling gradual release of active ingredient into weeds and the body of pests and controlled release of nutrients to plants.
Abstract: Abstract Nanoagrochemicals, such as nanopesticides, nanofertilizers or plant growth stimulating nanosystems, were primarily designed to increase solubility, enhance bioavailability, targeted delivery, controlled release and/or protection against degradation resulting in the reduced amount of applied active ingredients and finally in a decrease of dose-dependent toxicity/burden. This paper is a comprehensive up-to-date review related to the preparation and the biological activity of nanoformulations enabling gradual release of active ingredient into weeds and the body of pests and controlled release of nutrients to plants. The attention is also devoted to the decrease of direct environmental burden and economic benefits due to application of nanoformulations, where less amount of active ingredient is needed to achieve the same biological effect in comparison with bulk. The application of nanotechnology in the areas such as food packaging, food security, encapsulation of nutrients and development of new functional products is analysed. The use of nanoparticles in biosensors for detection of pathogens and contaminants as well as in DNA and gene delivery is discussed as well. Benefits and health risks of nanoagrochemicals are highlighted, and special attention is given to nanoecotoxicology and guidelines and regulatory documents related to the use of nanoformulations in agriculture and food industry.
90 citations
TL;DR: In most cases, compounds provided reliable bacteriostatic activity, except for 4-chloro-2-(4-chlorophenylcarbamoyl)phenyl decylcarbamate exhibiting bactericidal effect at 8h and at 24h, which is comparable or up to 250× higher than that of vancomycin, the standard in the treatment of serious MRSA infections.
52 citations
TL;DR: In this paper, the authors presented the preparation and characterization of silica-based nanocarriers loaded with piracetam, pentoxifylline, and pyridoxine (drugs from the class of nootropics), which are designed to enhance the permeation of the drugs from the circulatory system through the blood-brain barrier.
Abstract: The blood-brain barrier prevents the passage of many drugs that target the central nervous system. This paper presents the preparation and characterization of silica-based nanocarriers loaded with piracetam, pentoxifylline, and pyridoxine (drugs from the class of nootropics), which are designed to enhance the permeation of the drugs from the circulatory system through the blood-brain barrier. Their permeation was compared with non-nanoparticle drug substances (bulk materials) by means of an in vivo model of rat brain perfusion. The size and morphology of the nanoparticles were characterized by transmission electron microscopy. The content of the drug substances in silica-based nanocarriers was analysed by elemental analysis and UV spectrometry. Microscopic analysis of visualized silica nanocarriers in the perfused brain tissue was performed. The concentration of the drug substances in the tissue was determined by means of UHPLC-DAD/HRMS LTQ Orbitrap XL. It was found that the drug substances in silica-based nanocarriers permeated through the blood brain barrier to the brain tissue, whereas bulk materials were not detected in the brain.
47 citations
TL;DR: In this study, a series of twenty-two ring-substituted 6-hydroxynaphthalene-2-carboxanilides was prepared and characterized and derivatives substituted by trifluoromethyl, bromo, methyl and methoxy moieties showed higher activity against Mycobacterium tuberculosis than isoniazid and rifampicin.
44 citations
TL;DR: The most potent bactericidal agent was compound 1f exhibiting remarkable rapid concentration-dependent bactericidal effect even at 2x MIC even at 4, 6, and 8 h (with a reduction in bacterial count ranging from 3.08 to 3.75 log10 CFU/mL) after incubation against MRSA 63718.
Abstract: A series of nine substituted 2-hydroxy-N-[1-oxo-1-(phenylamino)alkan-2-yl]benzamides was assessed as prospective bactericidal agents against three clinical isolates of methicillin-resistant Staphylococcus aureus (MRSA) and S. aureus ATCC 29213 as the reference and quality control strain. The minimum bactericidal concentration was determined by subculturing aliquots from MIC determination onto substance-free agar plates. The bactericidal kinetics of compounds 5-chloro-2-hydroxy-N-[(2S)-3-methyl-1-oxo-1-[4-(trifluoromethyl)phenyl]aminobutan-2-yl]benzamide (1f), N-(2S)-1-[(4-bromophenyl)amino]-3-methyl-1-oxobutan-2-yl-4-chloro-2-hydroxybenzamide (1g), and 4-chloro-N-(2S)-1-[(3,4-dichlorophenyl)amino]-3-methyl-1-oxobutan-2-yl-2-hydroxybenzamide (1h) was established by time-kill assay with a final concentration of the compound equal to 1x, 2x, and 4x MIC; aliquots were removed at 0, 4, 6, 8, and 24 h time points. The most potent bactericidal agent was compound 1f exhibiting remarkable rapid concentration-dependent bactericidal effect even at 2x MIC at 4, 6, and 8 h (with a reduction in bacterial count ranging from 3.08 to 3.75 CFU/mL) and at 4x MIC at 4, 6, 8, and 24 h (5.30 CFU/mL reduction in bacterial count) after incubation against MRSA 63718. Reliable bactericidal effect against other strains was maintained at 4x MIC at 24 h.
36 citations
TL;DR: A series of fifteen new N-alkoxyphenylanilides of 3-hydroxynaphthalene-2-carboxylic acid was prepared and characterized and showed antibacterial and antimycobacterial activity against the tested strains comparable with or higher than that of the standards ampicillin or rifampicin.
Abstract: A series of fifteen new N-alkoxyphenylanilides of 3-hydroxynaphthalene-2-carboxylic acid was prepared and characterized. Primary in vitro screening of the synthesized compounds was performed against Staphylococcus aureus, three methicillin-resistant S. aureus strains, Mycobacterium tuberculosis H37Ra and M. avium subsp. paratuberculosis. Some of the tested compounds showed antibacterial and antimycobacterial activity against the tested strains comparable with or higher than that of the standards ampicillin or rifampicin. 3-Hydroxy-N-(2-propoxyphenyl)naphthalene-2-carboxamide and N-[2-(but-2-yloxy)-phenyl]-3-hydroxynaphthalene-2-carboxamide had MIC = 12 µM against all methicillin-resistant S. aureus strains; thus their activity is 4-fold higher than that of ampicillin. The second mentioned compound as well as 3-hydroxy-N-[3-(prop-2-yloxy)phenyl]-naphthalene-2-carboxamide had MICs = 23 µM and 24 µM against M. tuberculosis respectively. N-[2-(But-2-yloxy)phenyl]-3-hydroxynaphthalene-2-carboxamide demonstrated higher activity against M. avium subsp. paratuberculosis than rifampicin. Screening of the cytotoxicity of the most effective antimycobacterial compounds was performed using THP-1 cells, and no significant lethal effect was observed for the most potent compounds. The compounds were additionally tested for their activity related to inhibition of photosynthetic electron transport (PET) in spinach (Spinacia oleracea L.) chloroplasts. N-(3-Ethoxyphenyl)-3-hydroxynaphthalene-2-carboxamide (IC50 = 4.5 µM) was the most active PET inhibitor. The structure-activity relationships are discussed.
34 citations
TL;DR: The title compound forms a stable complex with PknB as is evident from the binding affinity values and the molecular docking results suggest that the compound might exhibit inhibitory activity against PKnB and this may result in development of new anti-tuberculostic agents.
33 citations
TL;DR: In this study, a series of twenty-two ring-substituted 8-hydroxyquinoline-2-carboxanilides was prepared and characterized and some of the tested compounds showed the antimycobacterial activity against M. paratuberculosis comparable with or higher than that of rifampicin.
30 citations
TL;DR: Molecular docking simulations against targets from Mycobacterium tuberculosis are reported and the results suggest that the compound might exhibit inhibitory activity against PknB.
15 citations
TL;DR: Based on the evaluated structure-PET inhibiting activity relationships (QSAR) it was confirmed that the inhibitory activity of the compounds depends on lipophilicity and electronic properties of the substituents on the acyl and the benzylamide fragments, the contribution of σ(1) being more significant than that of ρ(2).
Abstract: 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 IC 50 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 (IC 50 = 2.0 μmol/L), 3,5-dibromo-N-(3,4-dichlorobenzyl)-2-hydroxybenzamide (IC 50 = 2.3 μmol/L) and 3,5-dibromo-N-(4-chlorobenzyl)-2-hydroxybenzamide (IC 50 = 2.6 μmol/L) with activity comparable with that of the standard Diuron (IC 50 = 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-OCH 3 , 5-CH 3 , 5-Cl, 5-Br, 5-NO 2 , 4-OCH 3 , 4-Cl, 3,5-Cl and 3,5-Br) and the benzylamide fragment (R 2 = H, 4-OCH 3 , 4-CH 3 , 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 .
13 citations
TL;DR: A series of styrylquinolines and quinolineamides based on the 8-hydroxyquinoline moiety were investigated as potential antimycobacterial agents and appeared to be more effective than isoniazid and ciprofloxacin.
Abstract: A series of styrylquinolines and quinolineamides based on the 8-hydroxyquinoline moiety were investigated as potential antimycobacterial agents. The lipophilicity of the compounds was measured using RP-HPLC and the tests of their activity against Mycobacterium kansasii, the M. avium complex, M. smegmatis, M. abscessus, M. tuberculosis and M. avium paratuberculosis was performed. Several of the compounds that were obtained appeared to be more effective than isoniazid and ciprofloxacin. The 5,7-dinitro-8-hydroxyquinoline derivative possessed the highest potency against M. abscessus and M. Smegmatis, which was about twice as effective as ciprofloxacin, while 2-(2-hydroxystyryl)-8-hydroxyquinoline-7-carboxylic acid appeared to be comparable with the standard drugs that are against the M. avium complex. The structure activity relationships are discussed.
01 Dec 2015
TL;DR: Jampilek et al. as discussed by the authors presented a paper on the effects of environmental ecology on the performance of chemical drugs in the field of veterinary and pharmaceutical sciences in the Czech Republic.
Abstract: Matus Pesko, Jiri Kos, Katarina Kralova & Josef Jampilek* Department of Environmental Ecology, Faculty of Natural Sciences, Comenius University, Mlynska dolina Ch-2, 842 15 Bratislava, Slovakia Department of Chemical Drugs, Faculty of Pharmacy, University of Veterinary and Pharmaceutical Sciences, Palackeho 1/3, 612 42 Brno, Czech Republic Institute of Chemistry, Faculty of Natural Sciences, Comenius University, Mlynska dolina Ch-2, 842 15 Bratislava, Slovakia E-mail: josef.jampilek@gmail.com
TL;DR: By means of this rapid screening it was found out that the permeation of rutin through the skin increased linearly with time and was enhanced by both enantiomers of alaptide: approx.
Abstract: The investigation deals with the influence of permeation of rutin from carboxymethyl cellulose gel through full-thickness pig ear skin by (S)- and (R)-alaptide as potential excipients. Alaptide, 8-methyl-6,9-diazaspiro[4.5]decan-7,10-dione, is the original Czech compound. By means of this rapid screening it was found out that the permeation of rutin through the skin increased linearly with time and was enhanced by both enantiomers of alaptide: approx. 1.2-fold by (R)-alaptide and approx. 1.5-fold by (S)-alaptide.
TL;DR: In this paper, the authors summarized findings related to the risk of breast cancer due to exposure to following environmental contaminants: polycyclic aromatic hydrocarbons, polychlorinated biphenyls and dioxins, organochlorine pesticides, organophosphorous pesticides, bisphenol A, phthalates, parabens, organic solvents, atmospheric pollutants, metals, ionizing radiation, electromagnetic field and light pollution.
Abstract: Abstract Breast cancer is the most frequent cancer in women. It is believed that among the causes of breast cancer, hereditary factors account for only 5-10% of risk and the environmental exposures to environmental contaminants account for an additional 30-50% of risk. This paper summarizes findings related to the risk of breast cancer due to exposure to following environmental contaminants: polycyclic aromatic hydrocarbons, polychlorinated biphenyls and dioxins, organochlorine pesticides, organophosphorous pesticides, bisphenol A, phthalates, parabens, organic solvents, atmospheric pollutants, alkylphenols, metals, ionizing radiation, electromagnetic field and light pollution. Results obtained in in vitro experiments with breast cancer cell lines and in vivo with model rodents as well as in population based case-control studies are presented and the mode of action of individual environmental contaminants on mammary gland is discussed. Attention is also devoted to the effects of the timing of exposure to environmental contaminants (mainly exposition during development of the mammary gland) on breast cancer risk. Outcomes of professional exposure to some environmental contaminants on breast cancer risk are analysed as well Abstrakt Rak piersi jest najczęściej występującym rakiem u kobiet. Uważa się, że jedną z przyczyn tego raka są czynniki dziedziczne, którym przypisuje się jedynie 5-10% zachorowań, a ekspozycja na zanieczyszczenia środowiska stanowi dodatkowe 30-50%. Artykuł ten podsumowuje wyniki badań nad ryzykiem zachorowania na raka piersi w związku z narażeniem na następujące zanieczyszczenia środowiska: wielopierścieniowe węglowodory aromatyczne, polichlorowane bifenyle i dioksyny, pestycydy chloroorganiczne, pestycydy fosforoorganiczne, bisfenol A, ftalany, parabeny, rozpuszczalniki organiczne, zanieczyszczenia powietrza, alkilofenole, metale, promieniowanie jonizujące, pole elektromagnetyczne i zanieczyszczenie światłem. Przedstawiono wyniki badań uzyskane in vitro na liniach komórek raka piersi, in vivo na modelowych gryzoniach, a także wyniki badań przypadków w populacji, opartych na sposobie działania poszczególnych substancji zanieczyszczających środowisko na gruczoły sutkowe. Badano również wpływ czasu ekspozycji na zanieczyszczenia środowiska (głównie ekspozycja podczas rozwoju gruczołu sutkowego) na ryzyko zachorowania na raka piersi. Przeanalizowano także wpływ zawodowego narażenia na niektóre zanieczyszczenia na ryzyko zachorowania na raka piersi
01 Jan 2015
TL;DR: In this article, the most active Azone®-like compounds were considered in detail and classified according to their structure in terms of the approach of medicinal chemistry, and it was concluded that the family of Azone-like drugs will not probably provide any compound with significant enhancement activity.
Abstract: Azone® (1-dodecylazacycloheptan-2-one or laurocapram) is one of the most known and the most studied chemical penetration enhancers. Azone® analogues were considered in detail and classified according to their structure in terms of the approach of medicinal chemistry. General structure–activity relationships for the design of enhancing-effective Azone®-like molecules can be the following: e- or γ-lactams as a head group and an alkyl chain involving approximately 12 or (in case the ester group is inserted) 16 members, lipophilicity approx. 6, an unbranched (low branched) chain and low polar surface area (approx. 20 or 40–47), i.e. a limited number of polar atoms and molecular volume till 89 cm3/mol. With high probability, Azone® analogues represent compounds that show direct correlation between enhancement effect and irritation potential, and therefore it can be stated that the most active Azone®-like compounds described herein possess optimal irritation potential at maximum enhancing activity, and it is doubtful that any new enhancers within this group with better enhancement effect and irritation potential ratio could be found. Based on these facts, it can be finally concluded that the family of Azone®-like compounds will not probably provide any compound with significant enhancement activity.
01 Jan 2015
TL;DR: It was observed that under specific conditions alaptide is able to suppress permeation/absorption of compounds through the skin, which can limit the site of action of potentially hazardous/toxic drugs to skin surface.
Abstract: Based on the fact that alaptide is able to influence the creation and function of keratinocytes, it was supposed that alaptide could be used as a transdermal permeation modifier. Various APIs (bases, acids, salts, neutral molecules, small molecules, steroid-like molecules) were tested on their transdermal permeation in the mixture with micronized and/or nanonized alaptide as a transdermal permeation modifier. Also the influence of the type of formulation (ointment, cream, gel) on the effect of alaptide on skin was investigated intensively. It was observed that under specific conditions alaptide is able to suppress permeation/absorption of compounds through the skin, which can limit the site of action of potentially hazardous/toxic drugs to skin surface. The skin curative activity of alaptide can be helpful in reduction of possible skin irritant/injurious effects of permeating compounds. In transdermal application alaptide causes an increase or a decrease, in dependence on the used concentration, physical state and supporting medium (pharmaceutical formulation), in permeation/absorption of drugs into the skin and/or through the skin. The concentration of the used drug was increased at the place of administration, and/or the systemic concentration was increased, or it was ensured that drugs acted only on the skin surface/in the skin surface layer and did not penetrate into the deeper skin layers or did not have any systemic effect. Although alaptide was found in the 1980s of the twentieth century, even now it has great potential either as an active pharmaceutical ingredient or a permeation modifier.
TL;DR: It is indicated that alaptide modifies skin structure, which results in significantly enhanced permeation at long-term application.
Abstract: Alaptide, (S)-8-methyl-6,9-diazaspiro[4.5]decan-7,10-dione, is an original Czech compound; in this paper it is used as an excipient. The investigation deals with the affection of the permeation of indomethacin through full-thickness pig ear skin using a Franz diffusion cell from the donor vehicle of propylene glycol/water (1:1) using nanonized alaptide as a potential transdermal permeation enhancer. Alaptide was applied in ratio 1:10 (w/w) related to the amount of indomethacin. Nanonized alaptide showed an excellent rapid onset of enhancement effect, already at the 30 th minute after application, when the permeated amount of indomethacin was 5-fold more than in the formulation without alaptide. The enhancement ratio of nanonized alaptide was 5.6, which indicates that alaptide modifies skin structure, which results in significantly enhanced permeation at long-term application.
30 Oct 2015
TL;DR: In this paper, Antisolvent precipitation and emulsion solvent evaporation methods were used as techniques for preparation of twelve samples containing hydrochlorothiazide nanoparticles, ranging from 4.2 to 102.2 nm.
Abstract: Aqueous solubility and permeability through biomembranes are important parameters for drug bioavailability. Nanoparticles can be considered as a useful tool for improving properties of poorly soluble and/or permeable active ingredients. Hydrochlorothiazide (Class IV of BCS) was chosen as a model compound. Antisolvent precipitation – solvent evaporation and emulsion solvent evaporation methods were used as techniques for preparation of twelve samples containing hydrochlorothiazide nanoparticles. Water solutions of the surfactants sodium dodecyl sulfate and Tween 80 were used in mass concentrations of 1, 3 and 5%. Acetone and dichloromethane were used as solvents of model compound. The particle size of the prepared samples was measured by dynamic light scattering. The particle size ranged from 4.2 to 102.2 nm. Tween 80, that yielded nanoparticles <15 nm, was a preferable excipient to sodium dodecyl sulfate.
30 Oct 2015
TL;DR: In this paper, a series of eight 1-[(2-chlorophenyl)carbamoyl]naphthalen-2-yl N-alkyl carbamates was prepared and characterized.
Abstract: In this study a series of eight 1-[(2-chlorophenyl)carbamoyl]naphthalen-2-yl N‑alkylcarbamates was prepared and characterized. The discussed compounds were prepared by microwave-assisted and conventional synthesis. The compounds were tested for their activity related to inhibition of photosynthetic electron transport (PET) in spinach (Spinacia oleracea L.) chloroplasts. The PET-inhibiting activity of the compounds was moderate; the highest activity within the series of compounds was observed for 1-[(2-chlorophenyl)carbamoyl]naphthalen-2-yl N-propylcarbamate, and the compounds were found to inhibit PET in photosystem II.