Tunable release of silver nanoparticles from temperature-responsive polymer blends

Polymer blends of thermoresponsive poly(N-isopropylacrylamide) and poly(methyl methacrylate) with in situ synthesized silver nanoparticles (AgNPs) are proposed as stimuli-responsive antimicrobial materials. AgNPs were prepared in the semi-dried polymer blends by N-methyl-2-pyrrolidone reduction. Temperature controlled kinetic of silver release was examined for different weight ratios of the polymers. Synthesized AgNPs were characterized by transmission electron microscopy and temperature-dependent releasing was analyzed by ultraviolet–visible and atomic absorption spectroscopies. Temperature-dependent changes of polymer matrices were observed by confocal microscopy and infrared spectroscopy. It was shown that the polymer weight ratio determines both, starting time and kinetic of nanoparticle release. Antibacterial activities of the prepared material were demonstrated on Gram-positive Staphylococcus aureus (S. aureus) and gram-negative Pseudomonas aeruginosa (P. aeruginosa). Quantitative evaluation of antimicrobial efficacy of prepared materials was performed on the base of inhibition zone size. It was shown that prepared materials could serve as effective antibacterial coating with quick antimicrobial response.     

Biofilm-inactivating activity of silver nanoparticles: A comparison with silver ions

The antimicrobial activity of silver nanoparticles (AgNPs) against Pseudomonas aeruginosa PA01 planktonic and biofilm bacteria was examined; their activity was compared with that of silver ions. The inactivation of biofilms by AgNPs was greatly influenced by stirring, which caused an increased AgNP biosorption. Although the activity of AgNPs against planktonic cells was ca. 10% that of silver ions, their activity against biofilm cells was comparable to the silver ions’ activity at the same concentration after 90 min under stirring (ca. 3.5 log inactivation). AgNPs inactivated biofilms in a biosorption-dependent manner, whereas this was not the case for silver ions.     

Biosynthesis of silver nanoparticles from the culture supernatant of Bacillus marisflavi and their potential antibacterial activity

Silver nanoparticles (AgNPs) were prepared using culture supernatant of Bacillus marisflavi, a novel strain isolated from agricultural wastes. The formation of the AgNPs was confirmed using various analytical techniques such as UV–vis absorption spectroscopy, dynamic light scattering (DLS) and transmission electron microscopy (TEM). The antibacterial effect of synthesized nanoparticles was investigated against Pseudomonas aeruginosa. Furthermore, the mechanism of action of cell death of P. aeruginosa was confirmed by reactive oxygen species (ROS) generation in AgNPs treated cells and also our results clearly indicate that AgNPs could induce generation of ROS by dose dependent manner.     

Study on antibacterial activity of silver nanoparticles synthesized by gamma irradiation method using different stabilizers

Colloidal solutions of silver nanoparticles (AgNPs) were synthesized by gamma Co-60 irradiation using different stabilizers, namely polyvinyl pyrrolidone (PVP), polyvinyl alcohol (PVA), alginate, and sericin. The particle size measured from TEM images was 4.3, 6.1, 7.6, and 10.2 nm for AgNPs/PVP, AgNPs/PVA, AgNPs/alginate, and AgNPs/sericin, respectively. The influence of different stabilizers on the antibacterial activity of AgNPs was investigated. Results showed that AgNPs/alginate exhibited the highest antibacterial activity against Escherichia coli (E. coli) among the as-synthesized AgNPs. Handwash solution has been prepared using Na lauryl sulfate as surfactant, hydroxyethyl cellulose as binder, and 15 mg/L of AgNPs/alginate as antimicrobial agent. The obtained results on the antibacterial test of handwash for the dilution to 3 mg AgNPs/L showed that the antibacterial efficiency against E. coli was of 74.6%, 89.8%, and 99.0% for the contacted time of 1, 3, and 5 min, respectively. Thus, due to the biocompatibility of alginate extracted from seaweed and highly antimicrobial activity of AgNPs synthesized by gamma Co-60 irradiation, AgNPs/alginate is promising to use as an antimicrobial agent in biomedicine, cosmetic, and in other fields.     

Silver Nanoparticles from Oregano Leaves’ Extracts as Antimicrobial Components for Non-Infected Hydrogel Contact Lenses

The oregano leaves’ extract (ORLE) was used for the formation of silver nanoparticles (AgNPs(ORLE)). ORLE and AgNPs(ORLE) (2 mg/mL) were dispersed in polymer hydrogels to give the pHEMA@ORLE_2 and pHEMA@AgNPs(ORLE)_2 using hydroxyethyl–methacrylate (HEMA). The materials were characterized by X-ray fluorescence (XRF) spectroscopy, X-ray powder diffraction analysis (XRPD), thermogravimetric differential thermal analysis (TG-DTA), derivative thermogravimetry/differential scanning calorimetry (DTG/DSC), ultraviolet (UV-Vis), and attenuated total reflection mode (ATR-FTIR) spectroscopies in solid state and UV–Vis in solution. The crystallite size value, analyzed with XRPD, was determined at 20 nm. The antimicrobial activity of the materials was investigated against Gram-negative bacterial strains Pseudomonas aeruginosa (P. aeruginosa) and Escherichia coli (E. coli). The Gram-positive ones of the genus of Staphylococcus epidermidis (S. epidermidis) and Staphylococcus aureus (S. aureus) are known to be involved in microbial keratitis by the means of inhibitory zone (IZ), minimum inhibitory concentration (MIC), and minimum bactericidal concentration (MBC). The IZs, which developed upon incubation of P. aeruginosa, E. coli, S. epidermidis, and S. aureus with paper discs soaked in 2 mg/mL of AgNPs(ORLE), were 11.7 ± 0.7, 13.5 ± 1.9, 12.7 ± 1.7, and 14.3 ± 1.7 mm. When the same dose of ORLE was administrated, the IZs were 10.2 ± 0.7, 9.2 ± 0.5, 9.0 ± 0.0, and 9.0 ± 0.0 mm. The percent of bacterial viability when they were incubated over the polymeric hydrogel discs of pHEMA@AgNPs(ORLE)_2 was interestingly low (66.5, 88.3, 77.7, and 59.6%, respectively, against of P. aeruginosa, E. coli, S. epidermidis, and S. aureus) and those of pHEMA@ORLE_2 were 89.3, 88.1, 92.8, and 84.6%, respectively. Consequently, pHEMA@AgNPs(ORLE)_2 could be an efficient candidate toward the development of non-infectious contact lenses.     

Ecofriendly Synthesis of Silver Nanoparticles by Terrabacter humi sp. nov. and Their Antibacterial Application against Antibiotic-Resistant Pathogens

It is essential to develop and discover alternative eco-friendly antibacterial agents due to the emergence of multi-drug-resistant microorganisms. In this study, we isolated and characterized a novel bacterium named Terrabacter humi MAHUQ-38^T, utilized for the eco-friendly synthesis of silver nanoparticles (AgNPs) and the synthesized AgNPs were used to control multi-drug-resistant microorganisms. The novel strain was Gram stain positive, strictly aerobic, milky white colored, rod shaped and non-motile. The optimal growth temperature, pH and NaCl concentration were 30 °C, 6.5 and 0%, respectively. Based on 16S rRNA gene sequence, strain MAHUQ-38^T belongs to the genus Terrabacter and is most closely related to several Terrabacter type strains (98.2%–98.8%). Terrabacter humi MAHUQ-38^T had a genome of 5,156,829 bp long (19 contigs) with 4555 protein-coding genes, 48 tRNA and 5 rRNA genes. The culture supernatant of strain MAHUQ-38^T was used for the eco-friendly and facile synthesis of AgNPs. The transmission electron microscopy (TEM) image showed the spherical shape of AgNPs with a size of 6 to 24 nm, and the Fourier transform infrared (FTIR) analysis revealed the functional groups responsible for the synthesis of AgNPs. The synthesized AgNPs exhibited strong anti-bacterial activity against multi-drug-resistant pathogens, Escherichia coli and Pseudomonas aeruginosa. Minimal inhibitory/bactericidal concentrations against E. coli and P. aeruginosa were 6.25/50 and 12.5/50 μg/mL, respectively. The AgNPs altered the cell morphology and damaged the cell membrane of pathogens. This study encourages the use of Terrabacter humi for the ecofriendly synthesis of AgNPs to control multi-drug-resistant microorganisms.     

Rapid biological synthesis of silver nanoparticles using Kalopanax pictus plant extract and their antimicrobial activity

Silver nanoparticles (AgNPs) have promising potential in biomedicine, energy science, optics, and health care applications. We synthesized AgNPs using plant, Kalopanax pictus leaf extract. UV-visible spectrophotometric study showed the characteristic peak for AgNPs at wavelength 430 nm. The optical density at 430 nm increased after addition of plant leaf extract, indicating increase in formation of nanoparticles. Comparative time course analyses for AgNP synthesis carried out at different reaction temperatures (20, 60, and 90 °C) revealed higher reaction rate for K. pictus than Magnolia kobus plant leaf extract, which showed highest AgNP synthesis rate in the previous report. Electron microscopy analyses confirmed the presence of well dispersed AgNPs, predominantly with spherical shapes. In transmission electron microscopy, the particle size decreased with increase in temperature. Electron dispersive X-ray spectroscopy analyses indicated that Ag content increased with increase in reaction temperature. Fourier transform-infrared spectroscopy studies revealed capping of bioorganics from plant to the synthesized AgNPs. The antimicrobial activity of the synthesized AgNPs against Escherichia coli increased with increase in reaction temperature. The observations in this study will prove beneficial in approaching rapid synthesis of AgNPs and their antimicrobial application.     

Effect of Silver Nanoparticles on the In Vitro Regeneration,Biochemical, Genetic,and Phenotype Variation in Adventitious Shoots Produced from Leaf Explants in Chrysanthemum

Novel and unique properties of nanomaterials, which are not apparent in larger-size forms of the same material, encourage the undertaking of studies exploring the multifaced effects of nanomaterials on plants. The results of such studies are not only scientifically relevant but, additionally, can be implemented to plant production and/or breeding. This study aimed to verify the applicability of silver nanoparticles (AgNPs) as a mutagen in chrysanthemum breeding. Chrysanthemum × grandiflorum (Ramat.) Kitam. ‘Lilac Wonder’ and ‘Richmond’ leaf explants were cultured on the modified MS medium supplemented with 0.6 mg·L⁻¹ 6-benzylaminopurine (BAP) and 2 mg·L⁻¹ indole-3-acetic acid (IAA) and treated with AgNPs (spherical; 20 nm in diameter size; 0, 50, and 100 mg·L⁻¹). AgNPs strongly suppressed the capability of leaf explants to form adventitious shoots and the efficiency of shoot regeneration. The content of primary and secondary metabolites (chlorophyll a, chlorophyll b, total chlorophylls, carotenoids, anthocyanins, phenolic compounds) and the activity of enzymatic antioxidants (superoxide dismutase and guaiacol peroxide) in leaf explants varied depending on the AgNPs treatment and age of culture. Phenotype variations of ex vitro cultivated chrysanthemums, covering the color and pigment content in the inflorescence, were detected in one 50 mg·L⁻¹ AgNPs-derived and five 100 mg·L⁻¹ AgNPs-derived ‘Lilac Wonder’ plants and were manifested as the color change from pink to burgundy-gold. However, no changes in inflorescence color/shape were found among AgNPs-treated ‘Richmond’ chrysanthemums. On the other hand, the stem height, number of leaves, and chlorophyll content in leaves varied depending on the AgNPs treatment and the cultivar analyzed. A significant effect of AgNPs on the genetic variation occurrence was found. A nearly two-fold higher share of polymorphic products, in both cultivars studied, was generated by RAPD markers than by SCoTs. To conclude, protocols using leaf explant treatment with AgNPs can be used as a novel breeding technique in chrysanthemum. However, the individual cultivars may differ in biochemical response, the efficiency of in vitro regeneration, genetic variation, and frequency of induced mutations in flowering plants.     

Antimicrobial and anticoagulation activity of silver nanoparticles synthesized from the culture supernatant of Pseudomonas aeruginosa

Here, we describe biosynthesis of silver nanoparticles by reduction of aqueous Ag⁺ ions with the culture supernatant of Pseudomonas aeruginosa. The morphological, physiological, biochemical and molecular level identification of the strain GS1 resembles P. aeruginosa. The nanoparticles synthesized by P. aeruginosa were characterized by UV–vis spectroscopy, dynamic light scattering (DLS) and scanning electron microscopy (SEM). The size-distribution of nanoparticles was determined using a particle-size analyzer and the average particle-size was found to be 80 nm. The biological activities of the synthesized silver nanoparticles like antimicrobial activity were confirmed against Escherichia coli and Staphylococcus aureus and it have stable anti-coagulant effect.     

Influence of <Emphasis Type="Italic">Cissus quadrangularis</Emphasis> Stabilized AgNPs and Its Structural,Optical, Antibacterial Analysis: A Comparative Study

Silver nanoparticles (AgNPs) was synthesized by using AgCl precursor with the stabilizing agent Cissus quadrangularis by precipitation method and the obtained particles were characterized by X-ray diffraction (XRD) analysis, Field Emission Scanning Electron Microscope (FESEM) and UV–Visible (UV–Vis) analysis. The influence of a stabilizing agent on AgNPs was compared with non-stabilized AgNPs through the experimental analysis. The XRD patterns show pure face center cubic structure for both samples, whereas the crystallite size is found to be low in stabilizer used samples. FESEM image and the UV–Vis spectra show less agglomeration and blue shift respectively, for stabilizer used AgNPs, indicating small size particles. Photoluminescence spectra show the emission band at 390 nm for both samples. Antibacterial tests show good activity against Pseudomonas aeruginosa for stabilizer used AgNPs. The study concluded that Cissus quadrangularis can be used as a potential stabilizing agent for preparing AgNPs from AgCl, for optical and biomedical applications.     

Plant Antimicrobial Agents and Their Effects on Plant and Human Pathogens

To protect themselves, plants accumulate an armoury of antimicrobial secondary metabolites. Some metabolites represent constitutive chemical barriers to microbial attack (phytoanticipins) and others inducible antimicrobials (phytoalexins). They are extensively studied as promising plant and human disease-controlling agents. This review discusses the bioactivity of several phytoalexins and phytoanticipins defending plants against fungal and bacterial aggressors and those with antibacterial activities against pathogens affecting humans such as Pseudomonas aeruginosa and Staphylococcus aureus involved in respiratory infections of cystic fibrosis patients. The utility of plant products as “antibiotic potentiators” and “virulence attenuators” is also described as well as some biotechnological applications in phytoprotection.     

In vivo synthesis of nanomaterials in plants: location of silver nanoparticles and plant metabolism

Metallic nanoparticles (MeNPs) can be formed in living plants by reduction of the metal ions absorbed as soluble salts. It is very likely that plant metabolism has an important role in MeNP biosynthesis. The in vivo formation of silver nanoparticles (AgNPs) was observed in Brassica juncea, Festuca rubra and Medicago sativa. Plants were grown in Hoagland''s solution for 30 days and then exposed for 24 h to a solution of 1,000 ppm AgNO₃. In the leaf extracts of control plants, the concentrations of glucose, fructose, ascorbic acid, citric acid and total polyphenols were determined. Total Ag content in plant fractions was determined by inductively coupled plasma atomic emission spectroscopy. Despite the short exposure time, the Ag uptake and translocation to plant leaves was very high, reaching 6,156 and 2,459 mg kg⁻¹ in B. juncea and F. rubra, respectively. Ultrastructural analysis was performed by transmission electron microscopy (TEM), and AgNPs were detected by TEM X-ray microanalysis. TEM images of plant fractions showed the in vivo formation of AgNPs in the roots, stems and leaves of the plants. In the roots, AgNPs were present in the cortical parenchymal cells, on the cell wall of the xylem vessels and in regions corresponding to the pits. In leaf tissues, AgNPs of different sizes and shapes were located close to the cell wall, as well as in the cytoplasm and within chloroplasts. AgNPs were not observed in the phloem of the three plant species. This is the first report of AgNP synthesis in living plants of F. rubra. The contents of reducing sugars and antioxidant compounds, proposed as being involved in the biosynthesis of AgNPs, were quite different between the species, thus suggesting that it is unlikely that a single substance is responsible for this process.

MSC 2010

92 Biology and other natural sciences; 92Cxx Physiological, cellular and medical topics; 92C80 Plant biology     

Green Nanosilver as Reinforcing Eco-Friendly Additive to Epoxy Coating for Augmented Anticorrosive and Antimicrobial Behavior

Epoxy resin GY250 representing diglycidyl ethers of bisphenol-A (DGEBA) was reinforced with 1, 3 and 5wt % of surface functionalized silver nanoparticles (F-AgNPs) which were synthesized using Couroupita guianensis leaves extract with a view of augmenting the corrosion control property of the epoxy resin and also imparting antimicrobial activity to epoxy coatings on mild steel. Corrosion resistance of the coatings was evaluated by EIS, potentiodynamic polarization studies and cross scratch tests. AFM, SEM, HRTEM and EDX were utilized to investigate the surface topography, morphology and elemental composition of the coatings on MS specimens. Results showed that the corrosion resistance, hardness and T_g of the DGEBA/F-AgNPs coatings increased at 1wt % of F- AgNPs. The DGEBA/F-AgNPs coatings also offered manifold antimicrobial protection to the MS surfaces by inhibiting the growth of biofilm forming bacteria like P. aeruginosa, B. subtilis, the most common human pathogen E. coli and the most virulent human pathogenic yeast C. albicans.     

Self‐segregating hyperbranched polymer/silver nanoparticle hybrids in thermoplastic polyurethane films

Self‐segregating hyperbranched polymer (HBP) additives have been utilized to concentrate silver nanoparticles (AgNPs) at the air interface of polyurethane films. The limited spontaneous surface migration of the AgNPs was enhanced through the addition of appropriately functionalized HBPs. Both amine and thiol terminated additives were employed to allow interaction of the HBP with the nanoparticles. Both types of additives increased surface concentration of silver modestly, though the thiol‐terminated HBPs demonstrated nearly a seven‐fold enhancement of surface migration. It was also found that wholly‐aliphatic HBPs demonstrated only slightly reduced ability to bias AgNP concentration as compared to HBPs functionalized with perfluorinated chains. In addition, films containing 1% total silver concentration were tested for antimicrobial activity using the ASTM‐E 2180 protocol. Significant reduction of the microorganisms was observed for all samples, 6‐log reduction was achieved for the gram‐negative bacteria P. aeruginosa, the gram‐positive bacteria S. aureus, and the fungi C. albicans. © 2012 Wiley Periodicals, Inc. J. Appl. Polym. Sci., 2013     

Nano-Formulation Endows Quorum Quenching Enzyme-Antibiotic Hybrids with Improved Antibacterial and Antibiofilm Activities against Pseudomonas aeruginosa

The emergence of antibiotic resistant bacteria coupled with the shortage of efficient antibacterials is one of the most serious unresolved problems for modern medicine. In this study, the nano-hybridization of the clinically relevant antibiotic, gentamicin, with the bacterial pro-pathological cell-to-cell communication-quenching enzyme, acylase, is innovatively employed to increase its antimicrobial efficiency against Pseudomonas aeruginosa planktonic cells and biofilms. The sonochemically generated hybrid gentamicin/acylase nano-spheres (GeN_AC NSs) showed a 16-fold improved bactericidal activity when compared with the antibiotic in bulk form, due to the enhanced physical interaction and disruption of the P. aeruginosa cell membrane. The nano-hybrids attenuated 97 ± 1.8% of the quorum sensing-regulated virulence factors’ production and inhibited the bacterium biofilm formation in an eight-fold lower concentration than the stand-alone gentamicin NSs. The P. aeruginosa sensitivity to GeN_AC NSs was also confirmed in a real time assay monitoring the bacterial cells elimination, using a quartz crystal microbalance with dissipation. In protein-enriched conditions mimicking the in vivo application, these hybrid nano-antibacterials maintained their antibacterial and antibiofilm effectiveness at concentrations innocuous to human cells. Therefore, the novel GeN_AC NSs with complementary modes of action show potential for the treatment of P. aeruginosa biofilm infections at a reduced antibiotic dosage.     

Antimicrobial and Antioxidative Activity of Newly Synthesized Peptides Absorbed into Bacterial Cellulose Carrier against Acne vulgaris

The ongoing search for effective treatment of Acne vulgaris is concentrated, i.a., on natural peptides with antimicrobial properties. The aim of this work was the development of new amino acid derivatives with potential activity on dermal infections against selected microorganisms, including the facultative anaerobe C. acne. The peptides P1–P6 were synthesized via Fmoc solid phase peptide synthesis using Rink amide AM resin, analyzed by RP-HPLC-MS, FTIR, DPPH radical scavenging activity, and evaluated against C. acne and S. aureus, both deposited and non-deposited in BC. Peptides P1–P6 presented a lack of cytotoxicity, antimicrobial activity, or antioxidative properties correlated with selected structural properties. P2 and P4–P6 sorption in BC resulted in variable data, i.a., confirming the prospective topical application of these peptides in a BC carrier.     

Benzyl Isothiocyanate Attenuates Inflammasome Activation in Pseudomonas aeruginosa LPS-Stimulated THP-1 Cells and Exerts Regulation through the MAPKs/NF-κB Pathway

Inflammasomes are a group of intracellular multiprotein platforms that play important roles in immune systems. Benzyl isothiocyanate (BITC) is a constituent of cruciferous plants and has been confirmed to exhibit various biological activities. The modulatory effects of BITC on inflammasome-mediated interleukin (IL)-1β expression and its regulatory mechanisms in Pseudomonas aeruginosa (P. aeruginosa) LPS/ATP-stimulated THP-1 cells was investigated. Monocytic THP-1 cells were treated with phorbol myristate acetate (PMA) to induce differentiation into macrophages. Enzyme-linked immunosorbent assays (ELISA) were performed to measure the levels of IL-1β produced in P. aeruginosa LPS/ATP-exposed THP-1 cells. Western blotting was performed to examine the BITC modulatory mechanisms in inflammasome-mediated signaling pathways. BITC inhibited IL-1β production in P. aeruginosa LPS/ATP-induced THP-1 cells. BITC also inhibited activation of leucine-rich repeat protein-3 (NLRP3) and caspase-1 in P. aeruginosa LPS/ATP-induced THP-1 cells. Furthermore, we show that mitogen-activated protein kinase (MAPK) and nuclear factor-κB (NF-κB) activation in P. aeruginosa LPS was attenuated by BITC. These BITC-mediated modulatory effects on IL-1β production may have therapeutic potential for inflammasome-mediated disorders such as a nasal polyp.     

<Emphasis Type="Italic">Streptomyces ghanaensis</Emphasis> VITHM1 mediated green synthesis of silver nanoparticles: Mechanism and biological applications

We present the microbial green synthesis of silver nanoparticles (NPs) by Streptomyces ghanaensis VITHM1 strain (MTCC No. 12465). The secondary metabolites in the cell free supernatant of this bacterium when incubated with 1 mmol/L AgNO₃, mediated the biological synthesis of AgNPs. The synthesized AgNPs were characterized by UV-visible spectrum, X-ray diffraction (XRD), atomic force microscope, scanning electron microscopy equipped with energy dispersive spectroscopy, transmission electron microscopy, FT-IR spectroscopy, dynamic light scattering and zeta potential. They were highly stable and, spherical in shape with the average size of 30?50 nm. The secondary metabolites involved in the formation of AgNPs were identified gas chromatographymass spectrography. The 3D structure of the unit cell of the synthesized AgNPs was determined using XRD data base. The synthesized AgNPs exhibited significant antibacterial activity against tested bacterial pathogens, and did not show haemolysis on human red blood cells. This green synthesis could provide a new platform to explore and use AgNPs as antibacterial therapeutic agents.

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Evaluation of the Effects of Particle Sizes of Silver Nanoparticles on Various Biological Systems

Seven biological methods were adopted (three bacterial activities of bioluminescence, enzyme, enzyme biosynthetic, algal growth, seed germination, and root and shoot growth) to compare the toxic effects of two different sizes of silver nanoparticles (AgNPs). AgNPs showed a different sensitivity in each bioassay. Overall, the order of inhibitory effects was roughly observed as follows; bacterial bioluminescence activity ≈ root growth > biosynthetic activity of enzymes ≈ algal growth > seed germination ≈ enzymatic activity > shoot growth. For all bacterial activities (bioluminescence, enzyme, and enzyme biosynthesis), the small AgNPs showed statistically significantly higher toxicity than the large ones (p < 0.0036), while no significant differences were observed among other biological activities. The overall effects on the biological activities (except shoot growth) of the small AgNPs were shown to have about 4.3 times lower EC₅₀ (high toxicity) value than the large AgNPs. These results also indicated that the bacterial bioluminescence activity appeared to be an appropriate method among the tested ones in terms of both sensitivity and the discernment of particle sizes of AgNPs.     

Cholic Acid-Based Antimicrobial Peptide Mimics as Antibacterial Agents

There is a significant and urgent need for the development of novel antibacterial agents to tackle the increasing incidence of antibiotic resistance. Cholic acid-based small molecular antimicrobial peptide mimics are reported as potential new leads to treat bacterial infection. Here, we describe the design, synthesis and biological evaluation of cholic acid-based small molecular antimicrobial peptide mimics. The synthesis of cholic acid analogues involves the attachment of a hydrophobic moiety at the carboxyl terminal of the cholic acid scaffold, followed by the installation of one to three amino acid residues on the hydroxyl groups present on the cholic acid scaffold. Structure–activity relationship studies suggest that the tryptophan moiety is important for high antibacterial activity. Moreover, a minimum of +2 charge is also important for antimicrobial activity. In particular, analogues containing lysine-like residues showed the highest antibacterial potency against Gram-positive S. aureus. All di-substituted analogues possess high antimicrobial activity against both Gram-positive S. aureus as well as Gram-negative E. coli and P. aeruginosa. Analogues 17c and 17d with a combination of these features were found to be the most potent in this study. These compounds were able to depolarise the bacterial membrane, suggesting that they are potential antimicrobial pore forming agents.