Nanoparticles have drawn significant interest in a range of applications, ranging from biomedical to environmental sciences, due to their distinctive physicochemical characteristics. In this study, it was reported that simple biological production of Ag, Se, and bimetallic Ag2Se nanoparticles (NPs) with Pseudomonas aeruginosa is a promising, low-cost, and environmentally friendly method. For the first time in the scientific literature, Ag2Se nanoparticles have been generated via green bacterial biosynthesis. UV-vis spectroscopy, X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), transmission electron microscopy (TEM), scanning electron microscopy (SEM), and EDX were used to characterize the produced NPs. Biosynthesized NPs were examined for antibacterial, antibiofilm, and photocatalytic properties, and it was determined that the effects of NPs were dose dependent. The biosynthesized AgNPs, SeNPs, and Ag2Se NPs showed anti-microbial activity against Escherichia coli and Staphylococcus aureus. Minimal inhibitory concentrations (MICs) of E. coli and S. aureus were between 150 and 250 μg/mL. The NPs showed antibiofilm activity against E. coli and S. aureus at sub-MIC levels and reduced biofilm formation by at least 80% at a concentration of 200 μg/mL of each NPs. To photocatalyze the breakdown of Congo red, Ag, Se, and Ag2Se NPs were utilized, and their photocatalytic activity was tested at various concentrations and intervals. A minor decrease of photocatalytic degradation was detected throughout the NPs reuse operation (five cycles). Based on the encouraging findings, the synthesized NPs demonstrated antibacterial, antibiofilm, and photocatalytic properties, suggesting that they might be used in pharmaceutical, medical, environmental, and other applications.
- MeSH
- antibakteriální látky * farmakologie chemie chemická syntéza MeSH
- biofilmy * účinky léků MeSH
- Escherichia coli * účinky léků MeSH
- katalýza MeSH
- kovové nanočástice * chemie MeSH
- mikrobiální testy citlivosti * MeSH
- Pseudomonas aeruginosa * účinky léků metabolismus MeSH
- selen chemie farmakologie MeSH
- sloučeniny stříbra chemie farmakologie MeSH
- Staphylococcus aureus * účinky léků MeSH
- stříbro * chemie farmakologie metabolismus MeSH
- technologie zelené chemie * MeSH
- Publikační typ
- časopisecké články MeSH
Průmyslové kultivace jsou klíčovým zdroje mnoha produktů. Každá kultivace má své vlastní produkční kmeny, podmínky a apara‐ tury. Nejčastěji používané jsou mechanicky míchané bioreaktory, díky jejich efektivní homogenizaci a všestrannosti. Přesto nejsou kompletně kompatibilní s organismy citlivými na střižné síly. Pro kultivaci takových organismů je vhodnější probublávaná kolona. Obecné porovnání probublávané kolony s míchaným bioreaktorem je náročné, jelikož je každá kultivace specifická. Probublávané kolony jsou jednoduché a snadno konstruovatelné bioreaktory, které vyžadují menší počáteční kapitál v porovnání s mechanicky míchaným bioreaktorem. Probublávané kolony nemají vnitřní komponenty a složité mechanické části a jsou proto méně náročné na údržbu. Nicméně, nejsou tak všestranné jako míchané bioreaktory a jsou mnohem více účelově používané. Přesto jsou v dnešním průmyslu nenahraditelné, především při velkoobjemových kultivacích mechanicky citlivých buněk, jako produkce kyseliny citrónové nebo antibiotik. Přímé porovnání probublávané kolony s mechanicky míchaným bioreaktorem je složité. Existují studie zaměřené na porovnání těch‐ to bioreaktorů při specifických kultivacích. Volba mezi těmito bioreaktory přesto závisí na dané aplikaci, buněčné linii a ekonomice celého procesu.
Industrial cultivations are a key source of many products. Each cultivation requires a specific producing organism, conditions and apparatus. Stirred tanks are most commonly used bioreactors, due to their efficient homogenization and versatility. However, they are not entirely suitable for cultivation of shear sensitive cells. Bubble columns are more suitable option for shear sensitive cells. Overall comparison of bubble columns and stirred tanks is complicated, since every cultivation is situational. Bubble columns are simple and easy to build bioreactors, which require a smaller starting investment compared to STRs. In the case of BCs without the internals, they required less maintenance due to lack of complex mechanical parts. However, BCs are not as ver‐ satile as STRs and are much more situational. Even though, they are unreplaceable part of today’s industry, especially in cultivations of shear sensitive cells in high volumes, like production of citric acid or antibiotics. Direct comparison of BC and STR is difficult. Some studies have conducted tests with specific cultivations on minds. Still, the final choice between these bioreactors depends on application, cell line used and final economics of the entire process.
Silver nanoparticles (Ag. NPs) have shown a biological activity range, synthesized under different environment-friendly approaches. Ag. NPs were synthesized using aqueous crude extract (ACE) isolated from Plantago lanceolata. The ACE and Ag. NPs were characterized and assessed their biological and antioxidant activities. The existence of nanoparticles (NPs) was confirmed by color shift, atomic force microscopy (AFM), and UV-Vis's spectroscopy. The FT-IR analysis indicated the association of biomolecules (phenolic acid and flavonoids) to reduce silver (Ag+) ions. The SEM study demonstrated a sphere-shaped and mean size in the range of 30 ± 4 nm. The EDX spectrum revealed that the Ag. NPs were composed of 54.87% Ag with 20 nm size as identified by SEM and TEM. AFM has ended up being exceptionally useful in deciding morphological elements and the distance across of Ag. NPs in the scope of 23-30 nm. The TEM image showed aggregations of NPs and physical interaction. Ag. NPs formation also confirmed by XPS, DRS and BET studies. Ag. NPs showed efficient activity as compared to ACE, and finally, the bacterial growth was impaired by biogenic NPs. The lethal dose (LD50) of Ag. NPs against Agrobacterium tumefaciens, Proteus vulgaris, Staphylococcus aureus, and Escherichia coli were 45.66%, 139.71%, 332.87%, and 45.54%, with IC50 (08.02 ± 0.68), (55.78 ± 1.01), (12.34 ± 1.35) and (11.68 ± 1.42) respectively, suppressing the growth as compared to ACE. The antioxidant capacity, i.e., 2,2-diphenyl-1-picrylhydrazyl (DPPH) of Ag. NPs were assayed. ACE and Ag. NPs achieved a peak antioxidant capacity of 62.43 ± 2.4 and 16.85 ± 0.4 μg mL-1, compared to standard (69.60 ± 1.1 at 100 μg mL-1) with IC50 (369.5 ± 13.42 and 159.5 ± 10.52 respectively). Finally, the Ag. NPs synthesized by P. lanceolata extract have an excellent source of bioactive natural products (NP). Outstanding antioxidant, antibacterial activities have been shown by NPs and can be used in various biological techniques in future research.
- MeSH
- antibakteriální látky chemická syntéza chemie farmakologie MeSH
- antioxidancia chemická syntéza chemie farmakologie MeSH
- Bacteria účinky léků MeSH
- bakteriální infekce farmakoterapie MeSH
- kovové nanočástice chemie ultrastruktura MeSH
- lidé MeSH
- nanotechnologie MeSH
- Plantago chemie MeSH
- stříbro chemie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Background: Increasing resistance has resulted in an urgent need for new antimicrobial drugs. A systematic me-too approach was chosen to modify clinically used sulfonamides to obtain their imines. Methods & results: Twenty-five compounds were synthesized and evaluated for their antibacterial activity. The most active compounds were also investigated against methicillin- and trimethoprim/sulfamethoxazole (SMX)-resistant Gram-positive species. Staphylococci shared the highest susceptibility including resistant strains with minimum inhibitory concentrations from 3.91 μM (≥2.39 μg ml-1). Crucially, the compounds inhibit MRSA and trimethoprim/SMX-resistant Staphylococci without any cross-resistance. Modification of parent sulfonamides turned a bacteriostatic effect into a bactericidal effect. Toxicity for HepG2 and hemolytic properties were also determined. Conclusions: The presence of a dihalogenated salicylidene moiety is required for optimal activity. Based on toxicity, promising derivatives for further investigation were identified.
- MeSH
- aldehydy chemie farmakologie MeSH
- antibakteriální látky chemická syntéza chemie farmakologie MeSH
- bakteriální léková rezistence účinky léků MeSH
- iminy chemie farmakologie MeSH
- mikrobiální testy citlivosti MeSH
- molekulární struktura MeSH
- Staphylococcus účinky léků MeSH
- sulfonamidy chemie farmakologie MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
The search for novel antimycobacterial drugs is a matter of urgency, since tuberculosis is still one of the top ten causes of death from a single infectious agent, killing more than 1.4 million people worldwide each year. Nine Amaryllidaceae alkaloids (AAs) of various structural types have been screened for their antimycobacterial activity. Unfortunately, all were considered inactive, and thus a pilot series of aromatic esters of galanthamine, 3-O-methylpancracine, vittatine and maritidine were synthesized to increase biological activity. The semisynthetic derivatives of AAs were screened for their in vitro antimycobacterial activity against Mycobacterium tuberculosis H37Ra and two other mycobacterial strains (M. aurum, M. smegmatis) using a modified Microplate Alamar Blue Assay. The most active compounds were also studied for their in vitro hepatotoxicity on the hepatocellular carcinoma cell line HepG2. In general, the derivatization of the original AAs was associated with a significant increase in antimycobacterial activity. Several pilot derivatives were identified as compounds with micromolar MICs against M. tuberculosis H37Ra. Two derivatives of galanthamine, 1i and 1r, were selected for further structure optimalization to increase the selectivity index.
- MeSH
- alkaloidy amarylkovitých škodlivé účinky chemická syntéza farmakologie MeSH
- antibakteriální látky škodlivé účinky chemická syntéza farmakologie MeSH
- buňky Hep G2 MeSH
- lidé MeSH
- mikrobiální testy citlivosti MeSH
- Mycobacterium tuberculosis účinky léků MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
A series of novel acyclic nucleoside phosphonates (ANPs) was synthesized as potential adenylate cyclase inhibitors, where the adenine nucleobase of adefovir (PMEA) was replaced with a 5-substituted 2-aminothiazole moiety. The design was based on the structure of MB05032, a potent and selective inhibitor of fructose 1,6-bisphosphatase and a good mimic of adenosine monophosphate (AMP). From the series of eighteen novel ANPs, which were prepared as phosphoroamidate prodrugs, fourteen compounds were potent (single digit micromolar or submicromolar) inhibitors of Bordetella pertussis adenylate cyclase toxin (ACT), mostly without observed cytotoxicity in J774A.1 macrophage cells. Selected phosphono diphosphates (nucleoside triphosphate analogues) were potent inhibitors of ACT (IC50 as low as 37 nM) and B. anthracis edema factor (IC50 as low as 235 nM) in enzymatic assays. Furthermore, several ANPs were found to be selective mammalian AC1 inhibitors in HEK293 cell-based assays (although with some associated cytotoxicity) and one compound exhibited selective inhibition of mammalian AC2 (only 12% of remaining adenylate cyclase activity) but no observed cytotoxicity. The mammalian AC1 inhibitors may represent potential leads in development of agents for treatment of human inflammatory and neuropathic pain.
- MeSH
- adenylátcyklasový toxin antagonisté a inhibitory metabolismus MeSH
- antibakteriální látky chemická syntéza chemie farmakologie MeSH
- Bacillus anthracis účinky léků MeSH
- Bordetella pertussis účinky léků enzymologie MeSH
- buněčné linie MeSH
- inhibitory adenylylcyklasy chemická syntéza chemie farmakologie MeSH
- lidé MeSH
- mikrobiální testy citlivosti MeSH
- molekulární struktura MeSH
- myši MeSH
- neuralgie farmakoterapie MeSH
- organofosfonáty chemie farmakologie MeSH
- thiazoly chemie farmakologie MeSH
- vztah mezi dávkou a účinkem léčiva MeSH
- vztahy mezi strukturou a aktivitou MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
Lipophosphonoxins (LPPOs) are small modular synthetic antibacterial compounds that target the cytoplasmic membrane. First-generation LPPOs (LPPO I) exhibit an antimicrobial activity against Gram-positive bacteria; however they do not exhibit any activity against Gram-negatives. Second-generation LPPOs (LPPO II) also exhibit broadened activity against Gram-negatives. We investigated the reasons behind this different susceptibility of bacteria to the two generations of LPPOs using model membranes and the living model bacteria Bacillus subtilis and Escherichia coli. We show that both generations of LPPOs form oligomeric conductive pores and permeabilize the bacterial membrane of sensitive cells. LPPO activity is not affected by the value of the target membrane potential, and thus they are also active against persister cells. The insensitivity of Gram-negative bacteria to LPPO I is probably caused by the barrier function of the outer membrane with LPS. LPPO I is almost incapable of overcoming the outer membrane in living cells, and the presence of LPS in liposomes substantially reduces their activity. Further, the antimicrobial activity of LPPO is also influenced by the phospholipid composition of the target membrane. A higher proportion of phospholipids with neutral charge such as phosphatidylethanolamine or phosphatidylcholine reduces the LPPO permeabilizing potential.
- MeSH
- antibakteriální látky chemická syntéza farmakologie MeSH
- Bacillus subtilis chemie cytologie účinky léků MeSH
- Escherichia coli chemie cytologie účinky léků MeSH
- fosfatidylcholiny analýza metabolismus MeSH
- fosfatidylethanolaminy analýza metabolismus MeSH
- kationické antimikrobiální peptidy chemická syntéza farmakologie MeSH
- lipidové dvojvrstvy MeSH
- membránové potenciály účinky léků MeSH
- mikrobiální testy citlivosti MeSH
- permeabilita buněčné membrány MeSH
- vnější bakteriální membrána chemie účinky léků metabolismus MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
The rise in multidrug-resistant bacteria defines the need for identification of new antibacterial agents that are less prone to resistance acquisition. Compounds that simultaneously inhibit multiple bacterial targets are more likely to suppress the evolution of target-based resistance than monotargeting compounds. The structurally similar ATP binding sites of DNA gyrase and topoisomerase Ⅳ offer an opportunity to accomplish this goal. Here we present the design and structure-activity relationship analysis of balanced, low nanomolar inhibitors of bacterial DNA gyrase and topoisomerase IV that show potent antibacterial activities against the ESKAPE pathogens. For inhibitor 31c, a crystal structure in complex with Staphylococcus aureus DNA gyrase B was obtained that confirms the mode of action of these compounds. The best inhibitor, 31h, does not show any in vitro cytotoxicity and has excellent potency against Gram-positive (MICs: range, 0.0078-0.0625 μg/mL) and Gram-negative pathogens (MICs: range, 1-2 μg/mL). Furthermore, 31h inhibits GyrB mutants that can develop resistance to other drugs. Based on these data, we expect that structural derivatives of 31h will represent a step toward clinically efficacious multitargeting antimicrobials that are not impacted by existing antimicrobial resistance.
- MeSH
- adenosintrifosfát chemická syntéza chemie farmakologie MeSH
- antibakteriální látky chemická syntéza chemie farmakologie MeSH
- DNA gyráza metabolismus MeSH
- DNA-topoisomerasa IV antagonisté a inhibitory metabolismus MeSH
- Escherichia coli účinky léků enzymologie patogenita MeSH
- krystalografie rentgenová MeSH
- mikrobiální testy citlivosti MeSH
- molekulární struktura MeSH
- simulace molekulového dockingu MeSH
- Staphylococcus aureus účinky léků enzymologie patogenita MeSH
- vztah mezi dávkou a účinkem léčiva MeSH
- vztahy mezi strukturou a aktivitou MeSH
- Publikační typ
- časopisecké články MeSH
A series of 19 synthetic alkyl and thioalkyl glycosides derived from d-mannose, d-glucose and d-galactose and having C10-C16 aglycone were investigated for cytotoxic activity against 7 human cancer and 2 non-tumor cell lines as well as for antimicrobial potential on 12 bacterial and yeast strains. The most potent compounds were found to be tetradecyl and hexadecyl β-d-galactopyranosides (18, 19), which showed the best cytotoxicity and therapeutic index against CCRF-CEM cancer cell line. Similar cytotoxic activity showed hexadecyl α-d-mannopyranoside (5) but it also inhibited non-tumor cell lines. Because these two galactosides (18, 19) were inactive against all tested bacteria and yeast strains, they could be a target-specific for eukaryotic cells. On the other hand, β-D-glucopyranosides with tetradecyl (11) and hexadecyl (12) aglycone inhibited only Gram-positive bacterial strain Enterococcus faecalis. The studied glycosides induce changes in the lipid bilayer thickness and lateral phase separation at high concentration, as derived from SAXS experiments on POPC model membranes. In general, glucosides and galactosides exhibit more specific properties. Those with longer aglycone show high cytotoxicity and therefore, they are more promising candidates for cancer cell line targeted inhibition.
- MeSH
- antibakteriální látky chemická syntéza chemie farmakologie MeSH
- antitumorózní látky chemická syntéza chemie farmakologie MeSH
- buněčné linie MeSH
- buňky A549 MeSH
- buňky K562 MeSH
- difrakce rentgenového záření MeSH
- Enterococcus faecalis účinky léků MeSH
- galaktosa chemická syntéza chemie farmakologie MeSH
- glykosidy chemická syntéza chemie farmakologie MeSH
- HCT116 buňky MeSH
- lidé MeSH
- lipidové dvojvrstvy chemie MeSH
- maloúhlový rozptyl MeSH
- mikrobiální testy citlivosti MeSH
- molekulární struktura MeSH
- proliferace buněk MeSH
- sacharidové sekvence MeSH
- viabilita buněk účinky léků MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
Ionic liquids are increasingly used for their superior properties. Four water-immiscible ionic liquids (butyltriethylammonium bis(trifluoromethylsulfonyl)imide, octyltriethylammonium bis(trifluoromethylsulfonyl)imide, dodecyltriethylammonium bis(trifluoromethylsulfonyl)imide, butyl-3-methylimidazolium bis(trifluoromethylsulfonyl)imide) and their water miscible precursors (bromides) were synthesized in a microwave reactor and by conventional heating. The best conditions for microwave-assisted synthesis concerning the yield and the purity of the product are proposed. The heating in the microwave reactor significantly shortened the reaction time. Biocide and ecotoxic effects of synthesized ionic liquids and their precursors were investigated. All tested compounds had at least a little effect on the growth or living of microorganisms (bacteria or mold). The precursor dodecyltriethylammonium bromide was found to be the strongest biocide, but posed a risk to the aquatic environment due to its relatively high EC50 value in the test with Vibrio fischeri. We assumed that apart from the alkyl chain length, the solubility in water, duration of action, or type of anion can influence the final biocide and ecotoxic effect.
- MeSH
- Aliivibrio fischeri účinky léků MeSH
- amoniové sloučeniny chemie MeSH
- antibakteriální látky chemická syntéza farmakologie MeSH
- antifungální látky chemická syntéza chemie farmakologie MeSH
- ekotoxikologie metody MeSH
- imidazoly chemie MeSH
- iontové kapaliny chemická syntéza farmakologie MeSH
- kvartérní amoniové sloučeniny chemická syntéza farmakologie MeSH
- mikrovlny MeSH
- preklinické hodnocení léčiv metody MeSH
- Publikační typ
- časopisecké články MeSH
