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Given the growing interest in non-toxic materials with good anti-inflammatory and antimicrobial mechanical properties, this work focuses on preparing chitosan sponges with violacein and cannabis oil crosslinked with dialdehyde chitosan. The sponge was tested for its physicochemical and biological properties, presenting a high swelling rate, good thermal stability, and satisfactory mechanical properties. The obtained sponge's water vapor transmission rate was 2101 g/m2/day and is within the recommended values for ideal wound dressings. Notably, adding violacein favorably affected the material's porosity, which is essential for dressing materials. In addition, studies have shown that the designed material interacts with human serum albumin and exhibits good antioxidant and anti-inflammatory properties. The antibacterial properties of the prepared biomaterial were assessed using the Microtox test against A. fisherii (Gram-negative bacterium) and S. aureus (Gram-positive bacterium). The investigated material provides potential therapeutic benefits due to the synergistic action of chitosan, violacein, and cannabis oil so that it could be used as a dressing material. The natural origin of the substances could provide an attractive and sustainable alternative to traditional commercially available dressings.
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This study is focused on the utilization of naturally occurring salicylic acid and nicotinamide (vitamin B3) in the development of novel sustainable Active Pharmaceutical Ingredients (APIs) with significant potential for treating acne vulgaris. The study highlights how the chemical structure of the cation significantly influences surface activity, lipophilicity, and solubility in aqueous media. Furthermore, the new ionic forms of APIs, the synthesis of which was assessed with Green Chemistry metrics, exhibited very good antibacterial properties against common pathogens that contribute to the development of acne, resulting in remarkable enhancement of biological activity ranging from 200 to as much as 2000 times when compared to salicylic acid alone. The molecular docking studies also revealed the excellent anti-inflammatory activity of N-alkylnicotinamide salicylates comparable to commonly used drugs (indomethacin, ibuprofen, and acetylsalicylic acid) and were even characterized by better IC50 values than common anti-inflammatory drugs in some cases. The derivative, featuring a decyl substituent in the pyridinium ring of nicotinamide, exhibited efficacy against Cutibacterium acnes while displaying favorable water solubility and improved wettability on hydrophobic surfaces, marking it as particularly promising. To investigate the impact of the APIs on the biosphere, the EC50 parameter was determined against a model representative of crustaceansâArtemia franciscana. The majority of compounds (with the exception of the salt containing the dodecyl substituent) could be classified as "Relatively Harmless" or "Practically Nontoxic", indicating their potential low environmental impact, which is essential in the context of modern drug development.
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Curcumin is a natural compound with a great pharmaceutical potential that involves anticancer, anti-inflammatory, antioxidant, and neuroprotective activity. Unfortunately, its low bioavailability, instability, and poor water solubility significantly deteriorate its clinical use. Many attempts have been made to overcome this issue, and encapsulating curcumin in a hydrogel matrix may improve those properties. Hydrogel formulation is used in many drug delivery forms, including classic types and novel forms such as self-assembly systems or responsive to external factors. Reviewed studies confirmed better properties of hydrogel-stabilized curcumin in comparison to pure compound. The main enhanced characteristics were chemical stability, bioavailability, and water solubility, which enabled these systems to be tested for various diseases. These formulations were evaluated for wound healing properties, effectiveness in treating skin diseases, and anticancer and regenerative activity. Hydrogel formulation significantly improved biopharmaceutical properties, opening the opportunity to finally see curcumin as a clinically approved substance and unravel its therapeutic potential.
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Curcumina , Hidrogéis , Curcumina/química , Curcumina/farmacologia , Hidrogéis/química , Humanos , Solubilidade , Disponibilidade Biológica , Sistemas de Liberação de Medicamentos , Animais , Cicatrização/efeitos dos fármacos , Portadores de Fármacos/química , Antineoplásicos/química , Antineoplásicos/farmacologiaRESUMO
Mycoses of the skin are infectious diseases caused by fungal microorganisms that are generally treated with topical agents. However, such therapy is often ineffective and has to be supported by oral use of active substances, which, in turn, can cause many side effects. A good alternative for the treatment of deep-skin mycoses seems to be microneedles (MNs). The aim of this research was to fabricate and evaluate the properties of innovative MNs coated with a hydrogel as potential carriers for clotrimazole (CLO) in the treatment of deep fungal skin infections. A 3D printing technique using a photo-curable resin was employed to produce MNs, which were coated with hydrogels using a dip-coating method. Hydrogels were prepared with carbopol EZ-3 Polymer (Lubrizol) in addition to glycerol and triisopropanolamine. Clotrimazole was introduced into the gel as the solution in ethanol or was suspended. In the first step of the investigation, a texture analysis of hydrogels was prepared with a texture analyzer, and the drug release studies were conducted with the use of automatic Franz diffusion cells. Next, the release profiles of CLO for coated MNs were checked. The last part of the investigation was the evaluation of the antifungal activity of the prepared systems, and the inhibition of the growth of Candida albicans was checked with the diffusion and suspended-plate methods. The texture profile analysis (TPA) for the tested hydrogels showed that the addition of ethanol significantly affects the following studied parameters: hardness, adhesiveness and gumminess, causing a decrease in their values. On the other hand, for the gels with suspended CLO, better spreadability was seen compared to gels with dissolved CLO. The presence of the active substance did not significantly affect the values of the tested parameters. In the dissolution study, the results showed that higher amounts of CLO were released for MNs coated with a hydrogel containing dissolved CLO. Also, microbiological tests proved its efficacy against fungal cultures. Qualitative tests carried out using the diffusion method showed that circular zones of inhibition of fungal growth on the plate were obtained, confirming the hypothesis of effectiveness. The suspension-plate technique confirmed the inhibitory effect of applied CLO on the growth of Candida albicans. From the analysis of the data, the MNs coated with CLO dissolved in hydrogel showed better antifungal activity. All received results seem to be helpful in developing further studies for MNs as carriers of antifungal substances.
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Knowing about the antibiotic resistance, serotypes, and virulence-associated genes of Group B Streptococcus for epidemiological and vaccine development is very important. We have determined antimicrobial susceptibility patterns, serotype, and virulence profiles. The antibiotic susceptibility was assessed for a total of 421 Streptococcus agalactiae strains, isolated from pregnant women and neonates. Then, 89 erythromycin and/or clindamycin-resistant strains (82 isolates obtained from pregnant women and seven isolates derived from neonates) were assessed in detail. PCR techniques were used to identify the studied strains, perform serotyping, and assess genes encoding selected virulence factors. Phenotypic and genotypic methods determined the mechanisms of resistance. All tested strains were sensitive to penicillin and levofloxacin. The constitutive MLSB mechanism (78.2%), inducible MLSB mechanism (14.9%), and M phenotype (6.9%) were identified in the macrolide-resistant strains. It was found that macrolide resistance is strongly associated with the presence of the ermB gene and serotype V. FbsA, fbsB, fbsC, scpB, and lmb formed the most recurring pattern of genes among the nine surface proteins whose genes were analysed. A minority (7.9%) of the GBS isolates exhibited resistance to lincosamides and macrolides, or either, including those that comprised the hypervirulent clone ST-17. The representative antibiotic resistance pattern consisted of erythromycin, clindamycin, and tetracycline resistance (71.9%). An increase in the fraction of strains resistant to macrolides and lincosamides indicates the need for monitoring both the susceptibility of these strains and the presence of the ST-17 clone.
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Antibacterianos , Infecções Estreptocócicas , Recém-Nascido , Feminino , Humanos , Gravidez , Antibacterianos/farmacologia , Macrolídeos/farmacologia , Streptococcus agalactiae , Clindamicina/farmacologia , Gestantes , Polônia/epidemiologia , Infecções Estreptocócicas/tratamento farmacológico , Infecções Estreptocócicas/epidemiologia , Farmacorresistência Bacteriana/genética , Testes de Sensibilidade Microbiana , Lincosamidas/farmacologia , Eritromicina/farmacologiaRESUMO
Wound healing is a complex process; therefore, new dressings are frequently required to facilitate it. In this study, porous bacterial levan-based sponges containing cannabis oil (Lev@CBDs) were prepared and fully characterized. The sponges exhibited a suitable swelling ratio, proper water vapor transmission rate, sufficient thermal stability, desired mechanical properties, and good antioxidant and anti-inflammatory properties. The obtained Lev@CBD materials were evaluated in terms of their interaction with proteins, human serum albumin and fibrinogen, of which fibrinogen revealed the highest binding effect. Moreover, the obtained biomaterials exhibited antibacterial activity against Staphylococcus aureus and Pseudomonas aeruginosa, as well as being non-hemolytic material as indicated by hemolysis tests. Furthermore, the sponges were non-toxic and compatible with L929 mouse fibroblasts and HDF cells. Most significantly, the levan sponge with the highest content of cannabis oil, in comparison to others, retained its non-hemolytic, anti-inflammatory, and antimicrobial properties after prolonged storage in a climate chamber at a constant temperature and relative humidity. The designed sponges have conclusively proven their beneficial physicochemical properties and, at the preliminary stage, biocompatibility as well, and therefore can be considered a promising material for wound dressings in future in vivo applications.
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Quitosana , Camundongos , Animais , Humanos , Quitosana/química , Antibacterianos/farmacologia , Antibacterianos/química , Bandagens , Fibrinogênio , Anti-InflamatóriosRESUMO
Despite the recent dynamic development of medicine, influenza is still a significant epidemiological problem for people around the world. The growing resistance of influenza viruses to currently available antiviral drugs makes it necessary to search for new compounds or drug forms with potential high efficacy against human influenza A and B viruses. One of the methods of obtaining new active compounds is to chemically modify privileged structures occurring in the natural environment. The second solution, that is gaining more and more interest, is the use of modern drug carriers, which significantly improve physicochemical and pharmacokinetic parameters of the transported substances. Molecules known from the earliest times for their numerous therapeutic properties are glycyrrhizinic acid (GA) and glycyrrhetinic acid (GE). Both compounds constitute the main active agents of the licorice (Glycyrrhiza glabra, Leguminosae) root and, according to a number of scientific reports, show antiviral properties against both DNA and RNA viruses. The above information prompted many scientific teams around the world to obtain and test in vitro and/or in vivo new synthetic GA and GE derivatives against influenza A and B viruses. Similarly, in recent years, a significant amount of GA and GE-based drug delivery systems (DDS) such as nanoparticles, micelles, liposomes, nanocrystals, and carbon dots has been prepared and tested for antiviral activity, including those against influenza A and B viruses. This work systematizes the attempts undertaken to study the antiviral activity of new GA and GE analogs and modern DDS against clinically significant human influenza viruses, at the same time indicating the directions of their further development.
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Ácido Glicirretínico , Glycyrrhiza , Herpesvirus Cercopitecino 1 , Vírus da Influenza A , Vírus da Influenza B , Influenza Humana , Humanos , Antivirais/farmacologia , Antivirais/química , Sistemas de Liberação de Medicamentos , Ácido Glicirretínico/farmacologia , Glycyrrhiza/química , Ácido Glicirrízico/farmacologia , Ácido Glicirrízico/química , Influenza Humana/tratamento farmacológicoRESUMO
Due to the rapidly increasing problem of antibiotic resistance in recent years, the use of phthalocyanines as photosensitizers with their superior properties in photodynamic antimicrobial therapy (PACT) applications has become important. In this study, magnesium(II) 1,4,8,11,15,18,22,25-octakis(4-[4-butoxycarbonylphenoxy]butyloxy)phthalocyanine was used in the demetalation reaction in trifluoroacetic acid, and subsequently subjected to metalation reaction in dimethylformamide with zinc(II) acetate and bis(benzonitrile)palladium(II) chloride towards zinc(II) and palladium(II) derivatives. Three phthalocyanines, including a demetalated one as well as two metalated, in the core with zinc(II) and palladium(II) were characterized using 1D and 2D NMR spectroscopy and mass spectrometry. In addition, all macrocycles were subjected to absorption and emission studies as well as photostability tests. In a photochemical study, zinc(II) and palladium(II) phthalocyanine complexes appeared to be efficient singlet oxygen generators. There were noted quantum yields of singlet oxygen generation for zinc(II) phthalocyanine derivative in DMF and DMSO at 0.55 and 0.72, whereas for palladium(II) complex at 0.73 and 0.77, respectively. Liposomal formulations of phthalocyanine derivatives were prepared, and their activity was evaluated against a broad spectrum of antibiotic-resistant microorganisms, such as methicillin-resistant Staphylococcus aureus (MRSA), Escherichia coli (ESBL+), Candida albicans resistant to fluconazole, C. auris, and against dermatophytes. Phthalocyanine palladium(II) complex showed the highest bactericidal activity against all antibiotic-resistant microorganisms, including reducing C. auris growth at 3.54 log.
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Newly developed tetra- and octasubstituted methimazole-phthalocyanine conjugates as potential photosensitizers have been obtained. Synthesized intermediates and final products were characterized by the MALD-TOF technique and various NMR techniques, including 2D methods. Single-crystal X-ray diffraction was used to determine the crystal structures of dinitriles. The studied phthalocyanines revealed two typical absorption bands-the Soret band and the Q band. The most intense fluorescence was observed for octasubstituted magnesium(II) phthalocyanine in DMF (ΦFL = 0.022). The best singlet oxygen generators were octasubstituted magnesium(II) and zinc(II) phthalocyanines (Φ∆ 0.56 and 0.81, respectively). The studied compounds presented quantum yields of photodegradation at the level between 10-5 and 10-6. Due to their low solubility in a water environment, the liposomal formulations were prepared. Within the studied group, octasubstituted zinc(II) phthalocyanine at the concentration of 100 µM activated with red light showed the highest antibacterial activity against S. aureus equal to a 5.68 log reduction of bacterial growth.
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Fármacos Fotossensibilizantes , Staphylococcus aureus , Imidazóis , Indóis/química , Isoindóis , Magnésio/química , Fármacos Fotossensibilizantes/química , Oxigênio Singlete/metabolismo , Staphylococcus aureus/metabolismo , ZincoRESUMO
Wound healing and skin tissue regeneration remain the most critical challenges faced by medical professionals. Titanium(IV) oxide-based materials were proposed as components of pharmaceutical formulations for the treatment of difficult-to-heal wounds and unsightly scarring. A gallic acid-functionalized TiO2 nanomaterial (TiO2-GA) was obtained using the self-assembly technique and characterized using the following methods: scanning electron microscopy (SEM), transmission electron microscopy (TEM), nanoparticle tracking analysis (NTA), X-ray powder diffraction (XRPD), infrared spectroscopy (IR), Raman spectroscopy and thermogravimetry (TG). Additionally, physicochemical and biological tests (DPPH assay, Microtox® acute toxicity test, MTT assay) were performed to assess antioxidant properties as well as to determine the cytotoxicity of the novel material against eukaryotic (MRC-5 pd19 fibroblasts) and prokaryotic (Staphylococcus aureus, Escherichia coli, Candida albicans, Aliivibrio fischeri) cells. To determine the photocytotoxicity of the material, specific tests were carried out with and without exposure to visible light lamps (425 nm). Following the results, the TiO2-GA material could be considered an additive to dressings and rinsing suspensions for the treatment of difficult-to-heal wounds that are at risk of bacterial infections.
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This work investigated the potential of a novel formulation of eye drops containing a non-steroidal anti-inflammatory drug-choline salicylate (CS)-and hyaluronic acid (HA). Thus, these drops may exert both anti-inflammatory and regenerative activity. The experiment was conducted through the careful characterization of physicochemical properties, stability, and quality of eye drops. Moreover, microbiological analysis, as well as penetration and cytotoxic studies, were performed. The UV, HPLC-UV, and HPLC-MS/MS methods were used to determine the purity and stability of CS. The penetration rate of CS was assessed using a hydrophilic membrane and ex vivo porcine cornea model. Additionally, the cytotoxic effects were evaluated using the SIRC cell line. The interaction between HA and CS was tested using size-exclusion chromatography and IR spectrophotometry. As a result, HA increased the viscosity of the drops, which prolonged their contact with the ocular surface, thus ensuring more effective penetration of CS into the corneal structure. After long-term storage, an interaction in the pharmaceutical phase between CS and HA was observed. However, this interaction did not affect the viability of rabbit corneal cells. Our findings showed that eye drops with CS and HA, stored at 2-8 °C in light-protected conditions, met the criteria of stability and safety.
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INTRODUCTION AND OBJECTIVE: Pseudomonas aeruginosa is an opportunistic pathogen that causes difficult with treating infections, especially in the immunocompromised and patients with some underlying disease. The aim of the study is to assess the antibiotic resistance, biofilm formation, and the presence of genes encoding various virulence factors in clinical isolates of P. aeruginosa. MATERIAL AND METHODS: Seventy-three clinical isolates of Pseudomonas aeruginosa were tested. Antimicrobial Susceptibility Testing (AST) and carbapenemases production was performed in accordance with the EUCAST guidelines. The ability to form biofilm was assessed by crystal violet assay. Genes encoding selected virulence factors were detected using standard polymerase chain reaction (PCR). RESULTS: Among the 73 clinical isolates of P. aeruginosa, 41.1% were resistant to imipenem, 61.6% to meropenem, 30.1% to ciprofloxacin and 15.1% to tobramycin. Over 20% of isolates were producers of MBL. Antibiotic resistance profiling revealed that 23.3% of strains were sensitive to all antibiotics, 60.3% were LDR phenotype, and 16.4% were MDR phenotype. The majority of strains (73.6%) were strong-biofilm producers, 17.0% were moderate and 9.4% were weak biofilm producers. PCR analysis showed the presence of lasB, aprE and prpL genes in most of the tested strains (93.1%, 87.7% and 74.0%, respectively). Among strong biofilm producers, 22.2% were MDR, 63.0% of strains represented LDR phenotype, and 14.8% were sensitive to all antibiotics. Moderate and weak biofilm producers were LDR and sensitive phenotypes only (respectively, 58.3% and 42.9 - LDR, 41.7 and 51.7% - sensitive). CONCLUSIONS: High frequency of MDR strains and their ability of biofilm formation and virulence factors may be a threat to effective therapy, and can increase morbidity and mortality of infected patients.
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Antibacterianos/farmacologia , Proteínas de Bactérias/genética , Biofilmes , Farmacorresistência Bacteriana Múltipla , Infecções por Pseudomonas/microbiologia , Pseudomonas aeruginosa/efeitos dos fármacos , Fatores de Virulência/genética , Biofilmes/efeitos dos fármacos , Humanos , Testes de Sensibilidade Microbiana , Reação em Cadeia da Polimerase , Pseudomonas aeruginosa/genética , Pseudomonas aeruginosa/fisiologia , Fatores de Virulência/metabolismoRESUMO
These studies investigate the possibility of developing and using choline salicylate (CS) in ophthalmic therapy in the form of eye drops with increased viscosity. A 0.5% addition of hydroxypropyl methylcellulose (HPMC) was used as the viscosity increasing agent. The ability of CS to cross a hydrophilic membrane (regenerated cellulose membrane) was assessed by determining a rate constant consistent with zero order kinetics. In studies on a porcine cornea, the ability of CS to penetrate into the structure of the cornea was confirmed by determining the content of CS in the cornea after 5 minutes and 3 hours exposure to eye drops. The quality parameters of eye drops were assessed: pH, viscosity, osmolarity and microbiological purity. Stability tests were also performed on eye drops stored in unit minims packaging and in multi-dose bottle packaging. The following storage conditions were adopted: 40°C/75% RH, 25°C/60% RH, 2-8°C. The sensitivity of CS to light was also confirmed. The UV and HPLC-UV methods were used to assess the CS content, while the HPLC-UV and HPLC-MS/MS methods were used to assess the chromatographic purity.
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Antibacterianos , Espectrometria de Massas em Tandem , Animais , Colina/análogos & derivados , Combinação de Medicamentos , Estabilidade de Medicamentos , Soluções Oftálmicas , Salicilatos , Suínos , ViscosidadeRESUMO
The spread of bacterial resistance to antibiotics affects various areas of life. The aim of this study was to assess the occurrence of Pseudomonas aeruginosa, and other bacteria mainly from orders Enterobacterales and Staphylococcus in the pharmaceutical production sites, and to characterize isolated strains in the aspects of antibiotic resistance, biofilm formation, and presence of genes encoding virulence factors. Genes encoding selected virulence factors were detected using PCR techniques. Antimicrobial susceptibility testing was applied in accordance with the EUCAST recommendations. A total of 46 P. aeruginosa strains were isolated and 85% strains showed a strong biofilm-forming ability. The qualitative identification of genes taking part in Quorum Sensing system demonstrated that over 89% of strains contained lasR and rhlI genes. An antimicrobial susceptibility testing revealed nine strains resistant to at least one antibiotic, and two isolates were the metallo-ß-lactamase producers. Moreover, the majority of P. aeruginosa strains contained genes encoding various virulence factors. Presence of even low level of pathogenic microorganisms or higher level of opportunistic pathogens and their toxic metabolites might result in the production inefficiency. Therefore, the prevention of microbial contamination, effectiveness of sanitary and hygienic applied protocols, and constant microbiological monitoring of the environment are of great importance.
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Boron-dipyrromethene derivatives, including cationic and iodinated analogs, were obtained and subjected to physicochemical and in vitro photodynamic activity studies. Iodinated derivatives revealed a substantial heavy atom effect manifested by a bathochromic shift of the absorption band by about 30â nm and fluorescence intensity reduced by about 30-35 times, compared to that obtained for non-iodinated ones. In consequence, singlet oxygen generation significantly increased with ΦΔ values in the range 0.69-0.97. The in vitro photodynamic activity was evaluated on Gram-positive Staphylococcus aureus, Gram-negative Escherichia coli, and on human androgen-sensitive prostate adenocarcinoma cells (LNCaP). The novel cationic, iodinated BODIPY, demonstrated the highest activity toward all studied cells. An excellent cytotoxic effect was found against LNCaP cells with an IC50 value of 19.3â nM, whereas the viability of S. aureus was reduced by >5.6 log10 at 0.25â µM concentration and by >5.3 log10 in the case of E. coli at 5â µM. Thus, this analog seems to be a very promising candidate for the application in both anticancer and antimicrobial photodynamic therapy.
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Antibacterianos/farmacologia , Antineoplásicos/farmacologia , Compostos de Boro/farmacologia , Escherichia coli/efeitos dos fármacos , Fármacos Fotossensibilizantes/farmacologia , Staphylococcus aureus/efeitos dos fármacos , Antibacterianos/síntese química , Antibacterianos/química , Antineoplásicos/síntese química , Antineoplásicos/química , Compostos de Boro/síntese química , Compostos de Boro/química , Proliferação de Células/efeitos dos fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Testes de Sensibilidade Microbiana , Fotoquimioterapia , Fármacos Fotossensibilizantes/síntese química , Fármacos Fotossensibilizantes/química , Células Tumorais CultivadasRESUMO
Fungal based diseases currently affect nearly a quarter of the population around the world, which diseases are usually limited to superficial infections. Perversely, along with the development of modern medicine, cases of life-threatening systemic fungi are more and more often encountered. Compared to antibacterial drugs, significantly fewer fungicides are tested and introduced to clinical practice. At the same time, the drug resistance of pathological fungi is constantly growing. In addition to obtaining new derivatives of already-established classes of drugs, such as azoles, there is a growing interest in new compounds with potentially new mechanisms and application possibilities. Polymers are included in the flow of these studies, and among them - dendrimers. Dendrimers are a special type of polymers with a strictly defined structure and a plethora of functionalization possibilities. This allows them to not only be used as effective antifungal drug carriers but also enables them to exhibit antifungal activity per se. In this review, we have introduced to the epidemiology of fungal infections and summarized the aspects related to their control and therapy. Various polymers and dendrimers with antifungal activity were presented. In the subsequent sections antifungal acting dendrimers were discussed within three subchapters, based on their chemical structure: (i) amino acid-based dendrimers, (ii) amino based dendrimers, and (iii) other, which do not share similarities in structure. We have gathered and summarized the reports regarding the direct action of dendrimers on infectious fungi, as well as their effect when used as solubilizers, carriers or adjuvants with currently used antifungals. Use of dendrimers for the sensing of fungi or their metabolites are also considered. Special attention was also paid to the applications of dendrimers together with photosensitizers in antimicrobial photodynamic therapy.
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Anti-Infecciosos , Dendrímeros , Antifúngicos/farmacologia , Antifúngicos/uso terapêutico , Portadores de Fármacos , FungosRESUMO
Magnesium(II) tribenzoporphyrazines with phenoxybutylsulfanyl substituents were evaluated as photosensitizers in terms of their optical properties against wound bacteria. In the UV-vis spectra of analyzed tribenzoporphyrazines, typical absorption ranges were found. However, the emission properties were very weak, with fluorescence quantum yields in the range of only 0.002-0.051. What is important, they revealed moderate abilities to form singlet oxygen with the quantum yields up to 0.27. Under irradiation, the macrocycles decomposed via photobleaching mechanism with the quantum yields up to 8.64 × 10-5. The photokilling potential of tribenzoporphyrazines was assessed against Streptococcus pyogenes, Staphylococcus epidermidis, as well as various strains of Staphylococcus aureus, including methicillin-sensitive and-resistant bacteria. Both evaluated photosensitizers revealed high photodynamic potential against studied bacteria (>3 logs). S.aureus growth was reduced by over 5.9 log, methicillin-resistant S. aureus by 5.1 log, S.epidermidis by over 5.7 log, and S. pyogenes by over 4.7 log.
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Antibacterianos/síntese química , Compostos Macrocíclicos/síntese química , Fármacos Fotossensibilizantes/síntese química , Porfirinas/química , Animais , Antibacterianos/química , Antibacterianos/farmacologia , Humanos , Compostos Macrocíclicos/química , Compostos Macrocíclicos/farmacologia , Testes de Sensibilidade Microbiana , Estrutura Molecular , Fotodegradação , Fármacos Fotossensibilizantes/química , Fármacos Fotossensibilizantes/farmacologia , Pontos Quânticos , Oxigênio Singlete/metabolismo , Staphylococcus aureus/efeitos dos fármacos , Staphylococcus epidermidis/efeitos dos fármacos , Streptococcus pyogenes/efeitos dos fármacos , Infecção dos Ferimentos/prevenção & controleRESUMO
Streptococcus agalactiae is responsible for serious infections in newborn babies, pregnant women, and other patients. The aim of this study was to evaluate antimicrobial susceptibility, serotype distribution, and virulence determinants of the S. agalactiae isolates derived from clinical specimens considering the global increase of both antibiotic resistance and virulence. A total of 165 isolates were identified and serotyped by PCR techniques. Antimicrobial susceptibility was assessed by disk diffusion method, gradient diffusion method and VITEK® System. Virulence associated genes were investigated by PCR; ability to form biofilm was assessed using a microtiter plate assay. The highest observed MIC value for penicillin G was 0.12 µg/mL, seen in 8.5% of isolates. Resistance to erythromycin and clindamycin were found in 30.38% and 24.8% of the strains, respectively. The serotype III (32.73%), V (25.45%), and Ia (18.18%) were found as the most frequently represented. Previously unidentified strains in Poland, belonging to serotypes VI (three strains) and VII (one strain) were recognized. The presence of genes encoding various virulence factors as well as diverse ability to form biofilm were found. In conclusion, macrolide-resistance and decreased susceptibility to penicillin G were revealed signifying the increasing resistance among group B streptococci. Moreover, the presence of genes encoding various virulence factors and the ability to form biofilm were confirmed indicating their role in the pathomechanisms of the evaluated GBS infections.
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In the present study, the essential oils obtained by hydrodistillation of the organs of Eryngium maritimum and E. alpinum were analyzed by GC-FID-MS. The dominant constituents assessed in the essential oil of E. maritimum were germacrene D (45.2%) in the fruits; hexadecanoic acid (18.5%), menthol (16.8%), and menthone (10.9%) in the roots; 2,3,4-trimethylbenzaldehyde (11.3%) and germacrene D (10.5%) in the leaves; 2,3,4-trimethylbenzaldehyde (11.3%) in the shoot culture. In the case of E. alpinum, the main components of the leaf oil were: ß-elemenone (10.3%), germacrone (5.8%), two selinadienes (7.1% and 6.7%), and 1,8-cineole (5.3%), which were not found in the oil from shoot culture, whereas the shoot culture oil was dominated by hexadecanoic acid (15.5%), spathulenol (7.5%), (E)-ß-farnesene (4.9%), germacra-4(15),5,10(14)-trien-1α-ol (4.7%), and falcarinol (4.3%). The essential oils obtained from E. maritimum fruits and leaves of the intact plants, measured by the broth microdilution method, were the most active against T. mentagophytes and S. aureus. Moreover, the essential oil of leaves had the moderate activity against C. albicans and E. coli. The results showed that the chemical compositions of the essential oils differed decidedly between the two studied species and between the organs. Furthermore, the essential oil of E. maritimum may play an important role as antimicrobial agent.
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Infectious diseases constitute a serious problem for human health and life. Although many bacterial and fungal infections can be successfully cured by commonly used antibiotics, a new threat emerges in the form of microbial resistance. For this reason, researchers try to find not only new active pharmaceutical ingredients for conventional antibiotherapy but also try to develop new strategies of microbial inactivation. Photodynamic antimicrobial chemotherapy, which relies on reactive oxygen species generated in situ in the presence of a photosensitizer and with the light of an appropriate wavelength, is one of them. Porphyrazines have been considered as potential photosensitizers for anticancer and antimicrobial photodynamic therapy. In this study, three tribenzoporphyrazines with dendrimeric peripheral substituents were subjected to in vitro antimicrobial photocytotoxicity study. One magnesium(II) tribenzoporphyrazine with peripheral 3,5-bis(3,5-dimethoxybenzyloxy)benzylsulfanyl substituents was synthesized and subjected to physicochemical characterization using NMR, UV-Vis, and mass spectrometry techniques. In photochemical studies this molecule revealed moderate singlet oxygen generation ability (ΦΔDMF = 0.12, ΦΔDMSO = 0.13). The other two magnesium(II) tribenzoporphyrazines applied in the biological study were 4-[3,5-di(hydroxymethyl)phenoxy]butylsulfanyl-substituted tribenzoporphyrazine and 4-[3,5-bis(benzyloxy)benzyloxy]phenyl-substituted tribenzopyrazinoporphyrazine. For the assessment, three microbial strains were chosen: Gram-positive bacteria Staphylococcus aureus ATCC 25923, Gram-negative bacteria Escherichia coli ATCC 25922, and fungal strain Candida albicans ATCC 10231. Very high activity against Staphylococcus aureus at low 10-6 M concentration was recorded for magnesium(II) tribenzoporphyrazines with peripheral 3,5-bis(3,5-dimethoxybenzyloxy)benzylsulfanyl and 4-[3,5-di(hydroxymethyl)phenoxy]butylsulfanyl substituents with calculated log reductions of 4.4 and 4.8, respectively. It is worth noting that magnesium(II) tribenzoporphyrazine with 4-[3,5-di(hydroxymethyl)phenoxy]butylsulfanyl substituents revealed also 3.2 log reduction in bacterial growth at the concentration 10-7 M.