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The use of nanoparticles as drug‐carrying systems in medicine has received much attention, and on the other hand, the use of plants with medicinal properties has advantages over synthetic drugs. This study aims to improve the antibacterial and anti‐biofilm properties of Euphorbia hebecarpa plant extract using chitosan nanoparticles. Extraction were performed using the modified maceration and methanol solvent. The agar disc diffusion method was carried out to investigate the antimicrobial effects and MIC at an optical density (OD) of 630 nm. The anti‐biofilm agent's influence was measured at OD 570 nm, and the metabolic activity of bacteria in the damaged biofilm was determined using triphenyl tetrazolium chloride (TTC) staining. The nanoparticles were obtained by following the ionic gelation method and its characteristics were evaluated. Chitosan nanoparticles loaded with plant extract were found to be spherical shape with hydrodynamic diameter of 142 nm, a polydispersity index (PDI) of 0.184, a zeta potential of +28.6 mV. It was determined that the loading capacity (% LC) and encapsulation efficiency (% EE) percentages were 33% and 40%, respectively. The diameter of the inhibition zone in the agar disc diffusion test for both bacteria using nanoparticles loaded with the extract increased compared with control groups. Also, at a concentration of 4 mg/mL of loaded nanoparticles, 49.33% of Escherichia coli biofilm and 62.7% of Staphylococcus aureus biofilm were destroyed. The data obtained from the tests performed in this study show that the use of Euphorbia plant extract in the form of chitosan nanoparticles can have more antimicrobial and anti‐biofilm effects. [ABSTRACT FROM AUTHOR]

We developed and evaluated several new fused imidazo[1,2‐d][1,2,4]thiadiazolo[1,2,3]triazoles to see how they perform against bacteria and biofilms. Some compounds showed acceptable activity compared to the primary standard, Dicloxacillin. Some of the compounds demonstrated significant antibacterial activity against S. aureus, with MIC values ranging from 1.56–12.5 μg/mL. We also found anti‐biofilm properties in the potent compounds. The results showed that derivatives 3‐(4‐fluorophenyl)imidazo[1,2‐d] [1,2,3] triazolo[1,5‐b][1,2,4]thiadiazole 8,8‐dioxide and 3‐(3,5‐difluorophenyl)imidazo[1,2‐d][1,2,3]triazolo[1,5‐b][1,2,4] thiadiazole 8,8‐dioxide were strong antibacterial agents and effective MSSA and MRSA biofilm growth inhibitors. We conducted in silico studies to assess the molecular interactions of more potent compounds with TLR4 proteins (PDB: 3FXI, 3VQ1, 3RG1). Our findings revealed that 3‐(4‐chloro‐3,5‐dimethoxyphenyl)imidazo[1,2‐d][1,2,3]triazolo[1,5‐b] [1,2,4]thiadiazole 8,8‐dioxide, 3‐(3,5‐dichlorophenyl)imidazo[1,2‐d] [1,2,3]triazolo[1,5‐b][1,2,4] thiadiazole 8,8‐dioxide, and 3‐(4‐(trifluoromethyl)phenyl)imidazo[1,2‐d][1,2,3]triazolo[1,5‐b][1,2,4] thiadiazole 8,8‐dioxide exhibited more binding interactions than dicloxacillin. ADME of more potent compounds examined in this study and compounds could potentially inhibit the cytochrome P450 CYP2C19 isoform. [ABSTRACT FROM AUTHOR]

The escalation in infections from World Health Organization (WHO)‐listed priority pathogens has made development of new antibacterial agents a critical priority. In this context, use of therapeutic secondary metabolites (SMs) from Actinobacteria as new drugs presents a promising avenue. However, majority of them fail to reach market due to low aqueous solubility and hence low bioavailability. Even though nanosuspension technology has been effectively used to address these challenges, use of this technology for nanox02010;listed priority pathogens has made development of new antibacterial agents a critical priority. In thitransformation of crude metabolites from Actinobacteria is still an unattempted area. Herein, for the first time, development of water‐soluble nanosuspension of water‐insoluble therapeutic metabolites produced by Streptomyces californicus strain ADR1 to develop a biocompatible material to be used as potential nanomedicine is reported. The nanosuspension (N‐SM) is characterized by UV‐vis spectroscopy, transmission electron microscopy (TEM), Fourier transform infrared spectroscopy (FTIR), and dynamic light scattering (DLS). The nanosuspension reduces the MIC values by 50% against Gram‐positive priority pathogens and eradicates established biofilms with fivefold efficiency incomparison to SMs. The nanosuspension also displays antioxidant activity. The findings open up future possibilities of using this novel nanosuspension as an effective antibacterial agent in various therapeutic and biomedical applications like wound dressings, coatings on medical equipment, and surgical implants. [ABSTRACT FROM AUTHOR]

Background: Antimicrobial‐resistant Helicobacter pylori (H. pylori) poses a significant public health concern, especially given the limited therapeutic options for azithromycin‐resistant strains. Hence, there is a necessity for new studies to reconsider the use of azithromycin, which has diminished in effectiveness against numerous strains. Thus, we aimed to augment azithromycin's anti‐Helicobacter properties by combining it with curcumin in different formulations, including curcumin in clove oil, curcumin nano‐gold emulsion, and curcumin nanoemulsion. Methods: The antimicrobial activities of the investigated compounds, both individually and in combination with other anti‐Helicobacter drugs, were evaluated. Their antibiofilm and anti‐virulence properties were assessed using both phenotypic and genotypic methods, alongside molecular docking studies. Our findings were further validated through mouse protection assays and histopathological analysis. Results: We observed high anti‐Helicobacter activities of curcumin, especially curcumin nanoemulsion. A synergistic effect was detected between curcumin nanoemulsion and azithromycin with fraction inhibitory concentration index (FICI) values <0.5. The curcumin nanoemulsion was the most active anti‐biofilm and anti‐virulence compound among the examined substances. The biofilm‐correlated virulence genes (babA and hopQ) and ureA genes were downregulated (fold change <1) post‐treatment with curcumin nanoemulsion. On the protein level, the anti‐virulence activities of curcumin nanoemulsion were documented based on molecular docking studies. These findings aligned with histopathological scoring of challenge mice, affirming the superior efficacy of curcumin nanoemulsion/azithromycin combination. Conclusion: The anti‐Helicobacter activities of all curcumin physical forms pose significant challenges due to their higher minimum inhibitory concentration (MIC) values exceeding the maximum permissible level. However, using curcumin nanoemulsion at sub‐MIC levels could enhance the anti‐Helicobacter activity of azithromycin and exhibit anti‐virulence properties, thereby improving patient outcomes and addressing resistant pathogens. Therefore, more extensive studies are necessary to assess the safety of incorporating curcumin nanoemulsion into H. pylori treatment. [ABSTRACT FROM AUTHOR]

Biofilms are microbial communities that facilitate the pathogenesis of life‐threatening microbial infections through the glazing of mucosal surfaces or implanted devices thus protecting them from medications and increasing mortality rates. To discover a new class of antibiofilm agents 2‐amino‐1,3,4 thiadiazoles hybridized with pharmacologically active heterocycles were designed and synthesized. The compounds were characterized by infrared, nuclear magnetic resonance, mass spectroscopy and elemental analysis. All the compounds were assessed for their anti‐biofilm and anti‐virulence activity against P. aeruginosa and S. aureus. Quinoline‐substituted thiadiazoles were found to possess potent anti‐biofilm activity against P. aeruginosa and S. aureus. The molecular docking analysis further confirms the antibiofilm potential of the compounds. Density functional theory studies were carried out to investigate the electronic and molecular properties of the most active hybrids. [ABSTRACT FROM AUTHOR]

Colorectal cancer (CRC) is generally characterized by a high prevalence of Fusobacterium nucleatum (F. nucleatum), a spindle‐shaped, Gram‐negative anaerobe pathogen derived from the oral cavity. This tumor‐resident microorganism has been closely correlated with the occurrence, progression, chemoresistance and immunosuppressive microenvironment of CRC. Furthermore, F. nucleatum can specifically colonize CRC tissues through adhesion on its surface, forming biofilms that are highly resistant to commonly used antibiotics. Accordingly, it is crucial to develop efficacious non‐antibiotic approaches to eradicate F. nucleatum and its biofilms for CRC treatment. In recent years, various antimicrobial strategies, such as natural extracts, inorganic chemicals, organic chemicals, polymers, inorganic‐organic hybrid materials, bacteriophages, probiotics, and vaccines, have been proposed to combat F. nucleatum and F. nucleatum biofilms. This review summarizes the latest advancements in anti‐F. nucleatum research, elucidates the antimicrobial mechanisms employed by these systems, and discusses the benefits and drawbacks of each antimicrobial technology. Additionally, this review also provides an outlook on the antimicrobial specificity, potential clinical implications, challenges, and future improvements of these antimicrobial strategies in the treatment of CRC. [ABSTRACT FROM AUTHOR]

In this study, a new di‐substituted phthalonitrile derivative namely 2‐[2‐{(3,5‐bis (trifluoromethyl) phenyl) ethynyl}‐4,5 dicyanophenyl] malonate was synthesized. The cycloteramerization of the resultant compound in the presence of the related metal salts resulted in a number of metal {M=Co, Mn, and Lu} phthalocyanines. The newly synthesized macromolecules were used for the functionalization of gold nanorods. To study the effect of modification and metal ion on the biological properties of the gold nanorods, the biological features of the phthalocyanines, phthalocyanine‐gold nanorod conjugates, and gold nanorods were examined by performing different biological approaches. In this study, the anti‐diabetic activities of fluorinated phthalocyanines and their gold nanorod conjugates were examined for the first time using pancreatic alpha‐amylase. The antioxidant activities of the studied nano/structures were analyzed using 2,2‐diphenyl‐1‐picrylhydrazil (DPPH) radical scavenging assay. Their antimicrobial and antimicrobial photodynamic therapy activities (APDT) were investigated, as well. They exhibited good DNA cleavage activities. The highest biofilm inhibition activities were obtained 97.49 and 91.53 % for 200 mg/L of nanoconjugate (7) against S. aureus and P. aeruginosa, respectively. All the studied biological candidates also displayed effective microbial cell viability inhibition activities against E. coli. [ABSTRACT FROM AUTHOR]

Constructing a functional layer on the surface of commercial membrane (as a substrate) to inhibit the formation of biofilms is an efficient strategy to prepare an antibacterial anion exchange membrane (AEM). Herein, a rechargeable multifunctional anti‐biological system is reported by utilizing the mussel‐inspired L‐dopa connection function on commercial AEMs. Cobalt nanoparticles (Co NPs) and N‐chloramine compounds are deposited on the AEM surface by a two‐step modification procedure. The anti‐biofouling abilities of the membranes are qualitatively and quantitatively analyzed by adopting common Gram‐negative (E. coli) and Gram‐positive (S. aureus & Bacillus) bacteria as model biofouling organisms. The optimized membrane exhibits a high stability concerning the NaCl solution separation performance within 240 min. Meantime, the mechanism of the anti‐adhesion is un‐veiled at an atomic level and molecular dynamics (MD) simulation are conducted to measure the interaction, adsorption energy and average loading by using lipopolysaccharide (LPS) of E. coli. In view of the superior performance of antibacterial surfaces, it is believed that this work could provide a valuable guideline for the design of membrane materials with resistance to biological contamination. [ABSTRACT FROM AUTHOR]

Streptococcus mutans plays a major role in biofilm formation and pathogenic bacterial adhesion. Here we investigated the abilities of our isolates from diverse conventional sources to characterize the beneficial bacteria for inhibition of S. mutans. Enterobacter cloacae PS‐74, a beneficial bacteria isolated from yoghurt, is gram negative, rod shaped, and resistant to acid, bile salt, and amylase. PS‐74 cell‐free supernatants (CFS) demonstrated highest zone of inhibition of 29 ± 1.7 mm. Further, the minimum inhibitory concentration (MIC) value of CFS PS‐74 was recorded to be 10 μL and its minimum bactericidal concentration (MBC) value was found to be 15μL which led to 99.9% log reduction of S. mutans. Moreover, the biofilm formation was reduced by 84.91% at MIC15 of CFS PS‐74 which alleviate the dental caries formation by S. mutans. This is the first report on E. cloacae PS‐74, which was studied for its probiotic properties to inhibit S. mutans MTCC‐890 due to the production of organic acids and employed in oral treatment. [ABSTRACT FROM AUTHOR]

Biofilm‐associated infections have increased excessively over the recent years due to the increased population having impaired immune systems or as a result of certain medical conditions like transplantation, cancer, and any other chronic ailments. The abrupt enhancement of antibiotic resistance and enhanced utilization of biomedical devices offer new opportunities for microbial colonization leading to the development of microbial biofilms. Total eradication of recalcitrant microbial biofilms demands the adoption of a holistic approach and since the fungal metabolites enriched with bioactive compounds show efficacy in inhibiting the multiple factors behind biofilm formation, the anti‐biofilm activities of fungal metabolites need to be appraised. Being effective in preventing various steps of biofilm formation, including inhibition of surface adhesion and cell‐to‐cell communication through quorum quenching, blocking of quorum sensing receptors, and enzymes involved in microbial cell wall biosynthesis, targeting the virulence factors and finally killing of biofilm bound individual cells; myco‐metabolites are found effective as a potent holistic anti‐biofilm agent. The wide spectrum of bioactive substances of fungi and their anti‐biofilm activities against different pathogens and their multitarget characteristics are very promising in the field of treating biofilm infections. [ABSTRACT FROM AUTHOR]

An ideal tissue‐engineered dermal substitute should possess angiogenesis potential to promote wound healing, antibacterial activity to relieve the bacterial burden on skin, as well as sufficient porosity for air and moisture exchange. In light of this, a glass–ceramic (GC) has been incorporated into chitosan and gelatin electrospun nanofibers (240–360 nm), which MEFs were loaded on it for healing acceleration. The GC was doped with silver to improve the antibacterial activity. The bioactive nanofibrous scaffolds demonstrated antibacterial and superior antibiofilm activities against Gram‐negative and Gram‐positive bacteria. The nanofibrous scaffolds were biocompatible, hemocompatible, and promoted cell attachment and proliferation. Nanofibrous skin substitutes with or without Ag‐doped GC nanoparticles did not induce an inflammatory response and attenuated LPS‐induced interleukin‐6 release by dendritic cells. The rate of biodegradation of the nanocomposite was similar to the rate of skin regeneration under in vivo conditions. Histopathological evaluation of full‐thickness excisional wounds in BALB/c mice treated with mouse embryonic fibroblasts‐loaded nanofibrous scaffolds showed enhanced angiogenesis, and collagen synthesis as well as regeneration of the sebaceous glands and hair follicles in vivo. [ABSTRACT FROM AUTHOR]

Pathogenic bacteria infection is a serious threat to human public health due to the high morbidity and mortality rates. Nano delivery system for delivering antibiotics provides an alternative option to improve the efficiency compared to conventional therapeutic agents. In addition to the drug loading capacity of nanocarriers, which is typically around 10%, further lowers the drug dose that pathological bacteria are exposed to. Moreover, nanocarriers that are not eliminated from the body may cause side effects. These limitations have motivated the development of self-delivery systems that are formed by the self-assembly of different therapeutic agents. In this study, a vehicle-free antimicrobial polymer polyhexamethylene biguanide (PHMB, with bactericidal and anti-biofilm functions) hybrid gold nanoparticle (Au NPs, with photothermal therapy (PTT)) platform (PHMB@Au NPs) is developed. This platform exhibits an excellent synergistic effect to enhance the photothermal bactericidal effect for Staphylococcus aureus under near-infrared irradiation. Furthermore, the results showed that PHMB@Au NPs inhibit the formation of biofilms, quickly remove bacteria to promote wound healing through PTT in infection model in vivo, and even mediate the transition of macrophages from M1 to M2 type, and accelerate tissue angiogenesis. PHMB@Au NPs will have promising value as highly effective antimicrobial agents for patient management. [ABSTRACT FROM AUTHOR]

The traditional treatment for bacterial infections is the use of antibiotics, but the overuse of antibiotics can lead to the formation of multidrug‐resistant bacteria, and eventually lead to the formation of biofilms, which can resist the attack of the host immune system and the penetration of antibiotics in biofilms. Although biofilm‐targeted and stimulus‐responsive antibiotic delivery nanocarriers are available, the drugs that can be delivered is extremely limited. Therefore, an amphiphilic supramolecule Arg‐CD‐AcMH is constructed via host–guest interactions between β‐CD‐terminated arginine (Arg‐CD) and ferrocene‐terminated acetal‐modified maltoheptaose. The amphiphilic supramolecule Arg‐CD‐AcMH can self‐assemble with glucoamylase and glucose oxidase in aqueous solution to form spherical nanoparticles through hydrophilic–hydrophobic and electrostatic interactions. These nanoparticles can respond to the micro‐environment in the biofilm and selectively increase the level of H2O2 in the biofilm through the cascading catalytic effect of enzymes based on the self‐supply glucose, thus providing conditions for the release of anti‐biofilm active drug nitric oxide. [ABSTRACT FROM AUTHOR]

Abstract: Submonomer synthesis in solution and block‐coupling protocols were combined to prepare amphiphilic peptoid hexamers. The amphipathic character arises from the use of hydrophobic aliphatic tert‐butyl side‐chains imposing the cis‐amide backbone conformation and various cationic side‐chains periodically introduced each three residues. Evaluation of the effect on Gram‐positive and Gram‐negative bacterial strains as well as the capacity to impair biofilm formation and the toxicity of one selected compound allowed to highlight the potential of a short constrained peptoid carrying triazolium‐type cationic pendant groups. [ABSTRACT FROM AUTHOR]

Peri‐implant diseases are one of the main causes of dental implant failure. New strategies for dental implants manufacturing have been developed to prevent the accumulation of bacteria and related inflammatory reactions. The main aim of this work was to develop laser‐treated titanium surfaces covered with silver that generate a electrical dipole to inhibit the oral bacteria accumulation. Two approaches were developed for that purpose. In one approach a pattern of different titanium dioxide thickness was produced on the titanium surface, using a Q‐Switched Nd:YAG laser system operating at 1064 nm. The second approach was to incorporate silver particles on a laser textured titanium surface. The incorporation of the silver was performed by laser sintering and hot‐pressing approaches. The anti‐biofilm effect of the discs were tested against biofilms involving 14 different bacterial strains growth for 24 and 72 hr. The morphological aspects of the surfaces were evaluated by optical and field emission guns scanning electronical microscopy (FEGSEM) and therefore the wettability and roughness were also assessed. Physicochemical analyses revealed that the test surfaces were hydrophilic and moderately rough. The oxidized titanium surfaces showed no signs of antibacterial effects when compared to polished discs. However, the discs with silver revealed a decrease of accumulation of Porphyromonas gingivalis and Prevotella intermedia strains. Thus, the combination of Nd:YAG laser irradiation and hot‐pressing was effective to produce silver‐based patterns on titanium surfaces to inhibit the growth of pathogenic bacterial species. The laser parameters can be optimized to achieve different patterns, roughness, and thickness of the modified titanium layer regarding the type and region of the implant. [ABSTRACT FROM AUTHOR]

In the current study, niosome‐encapsulated tobramycin based on Span 60 and Tween 60 was synthesized and its biological efficacies including anti‐bacterial, anti‐efflux, and anti‐biofilm activities were investigated against multidrug resistant (MDR) clinical strains of Pseudomonas aeruginosa. The niosomal formulations were characterized using scanning electron microscopy, transmission electron microscopy, and dynamic light scattering measurement. The encapsulation efficiency was found to be 69.54% ±; 0.67. The prepared niosomal formulations had a high storage stability to 60 days with small changes in size and drug entrapment, which indicates that it is a suitable candidate for pharmaceutical applications. The results of biological study showed the anti‐bacterial activity via reduction of antibiotic resistance, enhanced anti‐efflux and anti‐biofilm activities by more folds in comparison to free tobramycin. In addition, niosome encapsulated tobramycin down‐regulated the MexAB‐OprM efflux genes, pslA and pelA biofilm related genes in MDR P. aeruginosa strains. The anti‐proliferative activity of formulation was evaluated against HEK293 cell lines, which exhibited negligible cytotoxicity against HEK293 cells. The finding of our study shows that encapsulation of tobramycin in niosome enhanced the antibacterial activity and reduced antibiotic resistance in MDR strains of P. aeruginosa comparing to free tobramycin and it can be considered as a favorable drug delivery system. [ABSTRACT FROM AUTHOR]

Prodrugs are pharmacologically attenuated derivatives of drugs that undergo bioconversion into the active compound once reaching the targeted site, thereby maximizing their efficiency. This strategy has been implemented in pharmaceuticals to overcome obstacles related to absorption, distribution, and metabolism, as well as with intracellular dyes to ensure concentration within cells. In this study, we provide the first examples of a prodrug strategy that can be applied to simple phenolic antimicrobials to increase their potency against mature biofilms. The addition of (acetoxy)methyl iminodiacetate groups increases the otherwise modest potency of simple phenols. Biofilm‐forming bacteria exhibit a heightened tolerance toward antimicrobial agents, thereby accentuating the need for new antibiotics as well as those, which incorporate novel delivery strategies to enhance activity toward biofilms. [ABSTRACT FROM AUTHOR]

Carbohydrates are versatile materials widely used for several applications including food, pharmaceuticals, cosmetics, and drug delivery systems due to their inherent properties such as non‐toxicity, biodegradability, and bio‐compatibility. Specifically, the urge on carbohydrate research is due to its significance in the biological system, for example, a glycoprotein found in the extracellular matrix, involved in signaling pathways, cell–cell interaction and cell–matrix interaction. Because of the increase in demand of glycolipids for biological applications, in this report, a set of three structurally related gluconamide‐based amphiphiles were synthesized from renewable resources, δ‐gluconolactone and cashew nut shell liquid. The molecular structure of the synthesized glycolipids was characterized by NMR and mass spectral techniques. Molecular self‐assembly of gluconamide‐based amphiphiles was investigated relative to the molecular structure and nature of the solvent used. Interestingly, the nature of the hydrophobic tail present in the glycolipids influences the self‐assembly pattern, which results in a hydrogel, organogel and highly insoluble nanorods. Gelation studies clearly revealed that the involvement of different magnitude of non‐covalent interactions such as hydrogen bonding, π–π stacking and van der Waals interaction. Morphology of self‐assembled architecture was investigated by optical microscopy, FESEM and FETEM analysis. The mechanism involved in the molecular self‐assembly has been deduced by small angle XRD analysis. Thermo reversibility and the thixotropic nature of the derived gels were identified by rheological measurements. Further, antimicrobial and biofilm inhibitory activity of gluconamide‐based amphiphiles were studied against various pathogenic bacterial strains Staphylococcus aureus, Listeria monocytogenes, Salmonella typhimurium, and Pseudomonas aeruginosa, and found effective in inhibition of biofilm and possesses the antibacterial property. Altogether, gluconamide‐based amphiphiles reported in this paper could be potentially used for some of the human problems caused by bacterial biofilms such as infections in the intravascular catheter, burn‐wounds, chronic sinusitis and implanted medical devices. [ABSTRACT FROM AUTHOR]

We had earlier used Oroidin, a 2‐aminoimidazole‐pyrrole natural microbial biofilm inhibitor, as a structural prototype to develop its 4/5‐acyl modified form as an anti‐biofilm lead for further optimization. Herein, as a part of our efforts towards that direction, we report the design, synthesis, as well as anti‐bacterial, anti‐biofilm, and fungal adhesion inhibition activities of various 4/5‐aroyl‐2‐aminoimidazoles. These simplified Oroidin analogues are moderately active against bacterial biofilms and attest to the need for an aliphatic acyl linker that was part of the original 4/5‐acyl modified Oroidin lead. From our studies, protonation propensity of the 2‐aminoimidazole group of the series emerges as an important pre‐requisite for potent antibiofilm activity. Also, the fungal biofilm screening studies identified analogue 8 b as an active molecule. [ABSTRACT FROM AUTHOR]

Widespread resistance to antibiotics amongst pathogens has become a tremendous challenge of high morbidity and mortality rates which increases the needs to exploring novel methods of treatment. An efficient antimicrobial procedure to root out pathogenic bacteria is photothermal therapy. In this study, antimicrobial effects of a polypyrrole–carbon nanocomposite (PPy‐C) upon laser irradiation in order to destroy the pathogenic gram‐positive bacterium, methicillin‐resistant Staphylococcus aureus (MRSA) were assessed. The bacterial cells were incubated with 500, 750 and 1000 μg ml−1 concentrations of PPy‐C and irradiated with an 808‐nm laser at a power density of 1.0 W cm−2. To indicate the biocompatibility and toxic effect of the nanocomposite without and with laser irradiation, the authors counted the number of CFUs and compared it to an untreated sample. Antibacterial mechanisms of PPy‐C were assessed through temperature increment, reactive oxygen species production, and protein and DNA leakages. Photothermal heating assay showed that 26°C temperature increases in the presence of 1000 µg ml−1 PPy‐C led to >98% killing of MRSA. Furthermore, 20 min radiation of near‐infrared light to PPy‐C in different concentrations indicated destruction and reduction in the MRSA biofilm formation. Therefore, PPy‐C was introduced as a photothermal absorber with a bactericidal effect in MRSA. [ABSTRACT FROM AUTHOR]

Literature reports suggest that pyrazoles and hydrazides are potential antimicrobial pharmocophores. Considering this fact, a series of nineteen conjugates containing hybrids of bis‐pyrazole scaffolds joined through a hydrazide linker were synthesized and further evaluated for their antimicrobial activity against a panel of Gram‐positive and Gram‐negative bacteria along with Candida albicansMTCC 3017 strain. Although the derivatives exhibited good antibacterial activity, some of the derivatives (13d, 13j, 13l, 13p, and 13r) showed excellent anti‐Candida activity with MICs values of 3.9 μg/ml, which was equipotent to that of the standard Miconazole (3.9 μg/ml), which has inspired us to further explore their anti‐Candida activity. The same compounds were also tested for anti‐biofilm studies against various Candida strains and among them, compounds 13l and 13r efficiently inhibited the formation of fungal biofilms. Field emission scanning electron micrographs revealed that one of the promising compound 13r showed cell damage and in turn cell death of the Candida strain. These potential conjugates (13l and 13r) also demonstrated promising ergosterol biosynthesis inhibition against some of the strains C. albicans, which were further validated through molecular docking studies. In silico computational studies were carried out to predict the binding modes and pharmacokinetic parameters of these conjugates. [ABSTRACT FROM AUTHOR]

Escherichia coli is the main etiological agent of urinary trait infections, able to form biofilms in indwelling devices, resulting in chronic infections which are refractory to antibiotics treatment. In this study, we investigated the antimicrobial and anti-biofilm properties exerted against E. coli ATCC 25922, by a set of peptoids and peptides modeled upon the peptide GN-2, previously reported as a valid antimicrobial agent. The putative antimicrobials were designed to evaluate the effect of cationicity, hydrophobicity and their partitioning on the overall properties against planktonic cells and biofilms as well as on LPS binding, permeabilization of Gram-negative bacteria membranes and hemolysis. The data demonstrated that peptides are stronger antimicrobials than the analogue peptoids which in return have superior anti-biofilm properties. In this study, we present evidence that peptides antimicrobial activity correlates with enhanced LPS binding and hydrophobicity but is not affected by partitioning. The data demonstrated that the enhanced anti-biofilm properties of the peptoids are associated with decreased hydrophobicity and increased penetration of the inner membrane, compared to that of their peptide counterpart, suggesting that the characteristic flexibility of peptoids or their lack of H-bonding donors in their backbone, would play a role in their ability to penetrate bacterial membranes. [ABSTRACT FROM AUTHOR]

Hit, Lead & Candidate Discovery Drug repurposing has become a recent trend in drug development programs, where previously developed drugs are explored for hit and redeveloped into potential therapeutic agents for new diseases. Globally, in any drug development program, a series of molecules are synthesized and evaluated for the hypothesized activity. Hits are developed into lead molecules or drugs, whereas the negative ones are shelved in the lab with no immediate use. We in this project took the previously sidelined small chemical molecules to the next level of utility, where previously developed in‐house small molecules library are tested for the unexplored biological relevant activity. As biofilm formation and quorum sensing play a vital role in bacterial pathogenesis, we believe that they could be one of the most effective targets for antimicrobial agents. In this study, we report the evaluation of 50 different compounds for anti‐biofilm and anti‐quorum sensing activity against Pseudomonas aeruginosa. Out of the screened compounds, three hydrazine‐carboxamide hybrid derivatives showed promising anti‐biofilm property and inhibition of pyocyanin production without any direct antimicrobial activity and cytotoxicity issues. Hydrazine‐carboxamide hybrids can be a new class and promising leads for further anti‐biofilm and anti‐virulence development against microbial infections. [ABSTRACT FROM AUTHOR]

Abstract: In the present study, a series of novel pyrazole‐thiazole hybrids (4a‐l) were designed, synthesized and assessed for their in vitro antimicrobial activity against both Gram‐positive and Gram‐negative pathogenic bacterial and fungal strains. Compounds derived from p‐CH3 phenyl (4b), p‐Br phenyl (4g), 8‐bromocoumarinyl (4k), and 6,8‐dibromocoumarinyl (4l) exhibited promising inhibitory activity against the tested bacterial strains with minimum inhibitory concentration (MIC)/minimum bactericidal concentration (MBC) spectrum of 1.9/7.8 μg/mL to 3.9/7.8 μg/mL. The compounds with p‐CH3 phenyl (4b), p‐OCH3 phenyl (4c), benzo[f]coumarinyl (4j), 8‐bromocoumarinyl (4k) substitutions showed their inhibitory potency against various Candida strains with MIC/minimum fungicidal concentration (MFC) values of 3.9/7.8 μg/mL. Also, anti‐biofilm and toxicity profile of the compounds was also tested. The biofilm inhibition results revealed that the compound 4 j exhibited promising activity with an IC50 value of 11.8 μM against S. aureus MTCC 96, while 4 k showed significant activity against S. aureus MLS16 MTCC 2940, K. planticola MTCC 530 and C. albicans MTCC 3017 with IC50 values of 12, 14 and 16 μM, respectively. The present study has emphasized that thiazole‐pyrazole hybrids with benzothiazole and coumarin scaffolds can be a novel and potent class of molecules with potential biological activities. [ABSTRACT FROM AUTHOR]

Abstract: A series of novel ethyl 9‐(trifluoromethyl) pyrido [2′, 3′:3,4]pyrazolo[1, 5‐a]quinazoline‐8‐carboxylate 4, 9‐(trifluoromethyl)pyrido[2′, 3′:3,4]pyrazolo[1, 5‐a]quinazoline‐8‐carboxylic acid 5, aryl amide functionalized pyrido[2′, 3′:3,4]pyrazolo [1, 5‐a] quinazoline derivatives 6 a‐f, secondary amide functionalized pyrido[2′, 3′:3,4] pyrazolo[1, 5‐a]quinazoline derivatives 7 a‐d and primary amide functionalized pyrido[2′, 3′:3,4]pyrazolo[1, 5‐a] quinazoline derivatives 8 a‐h were prepared starting from 2(1H)pyridone 1. All the compounds were evaluated for antibacterial activity against Gram‐positive and Gram‐negative bacterial strains and the compounds 5, 6 a, 6 c, 6 f, 7 a, 8 c, 8 f and 8 h exhibited promising antibacterial activity against various bacterial strains. Compound 5 showed high antibacterial (MIC value of 3.9 μg/mL) and broad‐spectrum anti bio‐film activity. Compound 5 and 8 b also showed good antifungal activity against the tested panel of various Candida strains. Molecular docking studies revealed that, the compound 5 and 8 b showed good binding interactions and corroborates with the antifungal results. All the compounds also screened for cytotoxicity and the compounds 7 d, 8 a, 8 b and 8 d exhibited above 90% inhibition against MCF7 (breast) cancer cell line and the compounds 6 d, 7 a, 8 a, 8 b, 8 f and 8 g exhibited above 90% inhibition against SKOV3 (ovarian) cell line, with reference to Doxorubicin (Control) drug in terms of inhibition. [ABSTRACT FROM AUTHOR]

Abstract: The aim of this study was to evaluate the chemical reactivity of 58S mesoporous bioactive glass (MBG) particles in as‐synthesized condition and after embedding propolis and cranberry antibiofilm compounds at different concentrations. MBG 58S was synthesized by alkali sol‐gel method with the addition of the triblock pluronic copolymer P123 as surfactant. Samples were characterized by physicochemical properties measurement, N2 adsorption/desorption analysis, and field emission gun scanning electron microscopy (FEGSEM) observations. MBG powders were immersed into 5 and 10 µg/mL propolis or cranberry solutions for 24 h. The chemical reactivity of the specimens was evaluated by FEGSEM, EDX, FTIR, Ca/P ratio, XRD, and sample weight gain analysis after being immersed in simulated body fluid (SBF) for 8, 24, and 72 h. MBG particles exhibited the expected chemical composition with a particle size distribution ranging from 1.44 to 955 µm, and a mean particle size of 154 µm. MBG particles exhibited a pore volume of 0.8 cc/g, pore radius of ∼2 nm, and surface area of 350.2 m2/g, according to BJH and BET analyses. A hydroxyl‐carbonate apatite (HCAp) layer was formed on all samples after SBF immersion for 72 h. Pure MBG showed the highest chemical reactivity after 72 h, with the resulting apatite layer exhibiting a Ca/P ratio of ∼1.6 in accordance to stoichiometric biological apatite. MBG embedding propolis and cranberry can be considered for future microbiological analysis since the presence of propolis or cranberry did not interfere with MBG's ability to develop a HCAp layer, which is an essential feature for bone regeneration applications. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 1614–1625, 2018. [ABSTRACT FROM AUTHOR]

Bioactive glass is an attractive biomaterial that has shown excellent osteogenic and angiogenic effects for oral bone repairing procedures. However, anti-biofilm potential related to such biomaterial has not been completely validated, mainly against multi-species biofilms involved in early tissue infections. The aim of the present study was to evaluate the anti-biofilm effect of 58 S bioactive glass embedding calcium bromide compounds at different concentrations. Bioactive glass free or containing 5, or 10 wt % CaBr2 was synthesized by alkali sol-gel method and then characterized by physco-chemical analyses and scanning electron microscopy (SEM). Then, samples were tested by microbiological assays using optical density, real time q-PCR, and SEM. Bioactive glass particles showed accurate chemical composition and an angular shape with a bimodal size distribution ranging from 0.6 to 110 µm. The mean particle size was around 29 µm. Anti-biofilm effect was recorded for 5 wt % CaBr2-doped bioactive glass against S. mitis, V. parvula, P. gingivais, S. gordoni, A. viscosus, F, nucleatum, P. gingivais. F. nucleatum, and P. gingivalis. Such species are involved in the biofilm structure related to infections on hard and soft tissues in the oral cavity. The incorporation of calcium bromide into bioactive glass can be a strategy to enhance the anti-biofilm potential of bioactive glasses for bone healing and infection treatment. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 1994-2003, 2017. [ABSTRACT FROM AUTHOR]

Host defense (antimicrobial) peptides, produced by all complex organisms, typically contain an abundance of positively charged and hydrophobic amino acid residues. A small synthetic peptide termed innate defense regulator (IDR-)1018 was derived by substantial modification of the bovine neutrophil host defense peptide bactenecin. Here, we review its intriguing properties that include anti-infective, anti-inflammatory, wound healing, and anti-biofilm activities. It was initially developed as an immune modulator with an ability to selectively enhance chemokine production and polarize cellular differentiation while suppressing/balancing the pro-inflammatory response. In this regard, it has demonstrated in vivo activity in murine models including enhancement of wound healing and an ability to protect against Staphylococcus aureus, multidrug resistant Mycobacterium tuberculosis, herpes virus, and inflammatory disorders, including cerebral malaria and neuronal damage in a pre-term birth model. More recently, IDR-1018 was shown, in a broad-spectrum fashion, to selectively target bacterial biofilms, which are adaptively resistant to many antibiotics and represent the most common growth state of bacteria in human infections. Furthermore, IDR-1018 demonstrated synergy with conventional antibiotics to both prevent biofilm formation and treat pre-existing biofilms. These data are consistent with a strong potential as an adjunctive therapy against antibiotic-resistant infections. Copyright © 2015 European Peptide Society and John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Antibiotic resistance is spreading at an alarming rate among pathogenic bacteria in both medicine and agriculture. Interfering with the intrinsic resistance mechanisms displayed by pathogenic bacteria has the potential to make antibiotics more effective and decrease the spread of acquired antibiotic resistance. Here, it is demonstrated that cranberry proanthocyanidin (cPAC) prevents the evolution of resistance to tetracycline in Escherichia coli and Pseudomonas aeruginosa, rescues antibiotic efficacy against antibiotic‐exposed cells, and represses biofilm formation. It is shown that cPAC has a potentiating effect, both in vitro and in vivo, on a broad range of antibiotic classes against pathogenic E. coli, Proteus mirabilis, and P. aeruginosa. Evidence that cPAC acts by repressing two antibiotic resistance mechanisms, selective membrane permeability and multidrug efflux pumps, is presented. Failure of cPAC to potentiate antibiotics against efflux pump‐defective mutants demonstrates that efflux interference is essential for potentiation. The use of cPAC to potentiate antibiotics and mitigate the development of resistance could improve treatment outcomes and help combat the growing threat of antibiotic resistance. [ABSTRACT FROM AUTHOR]