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Isolated enzymes serve as advantageous platforms for the fabrication of nanomaterials. The objective of this study was to fabricate silver nanoparticles (AgNPs) incorporated with Trametes versicolor laccase and evaluate their diverse biological properties. The AgNPs fabricated through laccase-mediated methods were characterized using various characterization techniques including UV-visible (UV-vis) spectroscopy, Energy-dispersive X-ray (EDX) spectroscopy, Dynamic light scattering (DLS) spectroscopy, Fourier transform infrared (FT-IR) spectroscopy, and Field emission scanning electron microscopy (FE-SEM). The results showed that the laccase-incorporated AgNPs were spherical in shape with a Z-average diameter of 19.40 nm and a zeta potential of -19.2 mV. The AgNPs exhibited significant dose-dependent in vitro α-amylase, urease, and DPPH free radical inhibitory activities, with maximum inhibitions of 83.49 ± 1.06 %, 68.95 ± 3.60 %, and 67.36 ± 3.40 %, respectively, at a concentration of 1000 μg mL -1 . Furthermore, the intrinsic pathway-mediated anticoagulant activity of the fabricated AgNPs was confirmed through the activated partial thromboplastin time (aPTT) assay, which serves as a global coagulation assay. Additionally, the laccase-incorporated AgNPs demonstrated antibacterial properties against both standard gram-positive strains of Staphylococcus epidermidis and Streptococcus mutans, with minimum inhibitory concentration (MIC) values of 2 and 4 μg mL -1 , and minimum bactericidal concentration (MBC) values of 16 and 16 μg mL -1 , respectively. The dose-dependent antibacterial performance of the AgNPs against both bacterial populations was also confirmed through flow cytometry. Moreover, the AgNPs exhibited 61.53 ± 3.17 % and 63.03 ± 1.44 % biofilm degradation against S. epidermidis and S. mutans, respectively, at the maximum tested concentration (20∗MIC)., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: The authors declare no conflict of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

In the current study, optimal supercritical fluid extract (SFE) of Lagerstroemia speciosa (LS) leaves at pressure 29.59 MPa (MPa), temperature 89.50 °C and extraction time 53.85 min was used to extract phenolic compounds for the synthesis of silver nanoparticles (AgNPs). The synthesis was studied for 0-20 h. Initially the synthesis of nanoparticles (SFELS-AgNPs) was confirmed using UV -spectroscopy. It demonstrated a maximum surface plasmon resonance at 430 nm. The crystallite dimension of nanoparticles was determined using X-ray diffraction (XRD) (13.47 nm), Transmission electron microscopy (TEM), zeta potential analysis and energy-dispersive X-ray analysis (EDAX) were used to analyze the morphology, surface charge and presence of differential elements in SFELS-AgNPs respectively. Developed nanoparticles revealed antimicrobial activity against 2 g-positive viz. Staphylococcus aureus and Bacillus cereus, and 3 g-negative bacteria viz. Klebsiella pneumonia, Pseudomonas aeruginosa and Escherichia coli. The nanoparticle showed a minimum inhibitory concentration (MIC) of 64 μg/ml whereas the minimum bactericidal concentration (MBC) 128 μg/ml against K. pneumonia. They significantly inhibited K. pneumonia biofilm formation which was confirmed using scanning electron microscopy (SEM). The results were encouraging compared to the standards drug Chloramphenicol and other controls. The generated nanoparticles have highly effective antimicrobial properties against pathogenic bacteria., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Inc.)

A new cocrystalline form of metronidazole (MET) with propyl gallate (PRO), referred to as MET-PRO, has been successfully synthesized and characterized. Structural characterization reveals that MET and PRO are present in a 1:1 ratio within the cocrystal lattice, with one water molecule equivalent incorporated into the structure. This arrangement facilitates the formation of MET-PRO heterodimers and multiple stable units, collectively constructing a three-dimensional supramolecular network. The solubility and permeability of the current cocrystal, along with the parent drug MET, are evaluated under physiological pH conditions. Experimental findings reveal that MET within the cocrystal exhibits a 1.54-2.37 folds increase in solubility and approximately a threefold improvement in permeability compared to its standalone form. Intriguingly, these concurrent enhancements in the physicochemical properties of MET lead to augmented antibacterial activity in vitro, evidenced by a reduction in minimum inhibitory concentration. Even more intriguingly, the enhanced physicochemical properties observed in vitro for the current cocrystal translate into tangible pharmacokinetic benefits in vivo, characterized by prolonged half-life and enhanced bioavailability. Consequently, this research not only introduces a fresh crystal structure for antibacterial medication but also presents approach for optimizing drug properties across in vitro and in vivo settings, while concurrently bolstering the antibacterial effectiveness of MET through pharmaceutical cocrystallization techniques., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Bi Qingqing reports financial support was provided by Qingdao Key Health Discipline Development Fund. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

The emergence of multidrug-resistant microbial species has become a global health concern, calling for novel antimicrobial agents. Peptoids, a class of synthetic peptidomimetics with unique structural properties, exhibit antimicrobial activity against a broad-spectrum of microbes, in addition to their stability to enzymatic degradation, selectivity, and relative ease of synthesis. Thus, peptoids have great potential in combating various drug-resistant pathogenic microbes. This review provides a comprehensive analysis of the recent advances in utilizing peptoids as effective antimicrobial agents against a wide range of bacteria, fungi, viruses, and parasites. In addition, some of the synthetic strategies and antimicrobial mechanisms are discussed. The imperfections of antimicrobial peptoids and the defects in current antimicrobial peptoids research are pointed out and promising directions for future development in peptoids are highlighted, to pave the way for innovating better antimicrobial peptoids to address the challenges posed by multidrug-resistant microbial species., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Masson SAS. All rights reserved.)

To survive in the metal-scarce environment within the host, pathogens synthesize various small molecular metallophores to facilitate the acquisition of transition metals. The cobalt and nickel transporter (Cnt) system synthesizes and transports staphylopine, a nicotianamine-like metallophore, and serves as a primary transition metal uptake system in Gram-positive bacteria including the human pathogen Staphylococcus aureus. In this study, we report the design of the first inhibitor of the Cnt system by targeting the key aminobutanoyltransferase CntL which is involved in the biosynthesis of staphylopine. Through structure-guided fragment linking and optimization, a class of acceptor-adenosine dual-site inhibitors against S. aureus CntL (SaCntL) were designed and synthesized. The most potent inhibitor, compound 9, demonstrated a ΔT m value of 9.4 °C, a K d value of 0.021 ± 0.004 μM, and an IC 50 value of 0.06 μM against SaCntL. The detailed mechanism by which compound 9 inhibits SaCntL has been elucidated through a high-resolution co-crystal structure. Treatment with compound 9 resulted in a moderate downregulation of intracellular concentrations of iron, nickel, and cobalt ions in the S. aureus cells cultured in the metal-scarce medium, providing the first chemical validation of the important role of Cnt system in bacterial metal acquisition. Our findings pave the way for the development of CntL-based antibacterial agents in future., Competing Interests: Declaration of competing interest The authors declare that there is no conflict of interest., (Copyright © 2024 Elsevier Masson SAS. All rights reserved.)

The striking rise of infections caused by multidrug-resistant pathogens has evolved as a serious threat to public health worldwide. To develop new antibacterials to combat multidrug-resistant bacteria, a novel class of amphiphilic chalcone derivatives serving as antimicrobial peptidomimetics was designed and synthesized. Among them, the most promising compound 14b displayed broad-spectrum antimicrobial activity against both Gram-positive bacteria (MICs = 0.5-1 μg/mL) and Gram-negative bacteria (MICs = 1-32 μg/mL), low hemolytic activity, and good membrane selectivity. Moreover, compound 14b exhibited rapid bactericidal action, a low probability of developing resistance, high proteolytic stability, and strong capabilities of inhibiting and destroying bacterial biofilms. Further mechanism investigations revealed that compound 14b possessed strong membrane-disrupting abilities and could disintegrate the integrity of bacterial cell membranes by destroying transmembrane potential and enhancing membrane permeability, and causing the generation of intracellular ROS and the leakage of DNA and proteins, ultimately leading to bacterial death. More importantly, compound 14b also showed excellent in vivo therapeutic potency in a mouse septicemia model infected by both Gram-positive and Gram-negative bacteria, indicating its potential to be an antibacterial agent to confront bacterial infections., Competing Interests: Declaration of competing interest The authors declare that this study was carried out only with public funding. There is no funding or no agreement with commercial for profit firms., (Copyright © 2024 Elsevier Masson SAS. All rights reserved.)

There is growing interest in developing monotherapy drugs that treat inflammation caused by microbial infections, focusing on dual antimicrobial and anti-inflammatory agents with minimal side effects and high safety margins. This study synthesized and characterized a library of novel cis-4-ferrocenylazetidin-2-ones, evaluating their antimicrobial and anti-inflammatory activities. These organometallic monocyclic β-lactams showed moderate in vitro antimicrobial activity against various standard microbial strains, including yeasts and Gram-negative and Gram-positive bacteria. Some compounds overcame the resistance of clinical Staphylococcus aureus isolates. Traditionally, monocyclic β-lactams target Gram-negative bacilli, but adding a ferrocene moiety and substituting the COOH group near the N-1 position with a non-ionizable ester group (COOR) extended their activity spectrum. The anti-inflammatory properties were assessed in macrophage-based models, revealing non-cytotoxicity below 10 μM. Two compounds were shown to be strong and selective arginase inhibitors, while five others effectively suppressed excessive NO formation without affecting basal NO production. The presence of a phenoxy group at C-3 of the β-lactam ring appeared to be crucial for selective NO inhibition. These hybrids did not scavenge NO but inhibited NO synthesis by suppressing iNOS expression. Overall, two novel hybrids were identified as promising hit candidates for treating infection-induced inflammatory reactions., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Masson SAS. All rights reserved.)

Mixed infections caused by drug-resistant bacteria and fungi pose a severe threat to human health, and multi-target drugs may provide an effective approach to combat drug-resistant pathogens. Therefore, this study aimed to investigate the efficacies of some oleanolic acid (OA) derivatives against multidrug-resistant (MDR) bacteria and fungi using in vitro and in vivo experiments. Novel amphiphilic OA derivatives were designed and optimised, in which compounds G1 and J1 exhibited effective antimicrobial activity (MICs = 1-2 μg/mL), high selectivity against MDR strains, rapid bactericidal activity, and good predictive pharmacokinetics. Mechanistically, both compounds prevented drug resistance by disrupting the bacterial cell membrane, inserting into the DNA, and binding to DNA gyrase. Additionally, J1 reduced microbial count in a mouse MRSA skin infection model and accelerated wound healing much better than vancomycin. Conclusively, this study presents a new class of potential drugs for resistant bacteria and fungi., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2024 Elsevier Masson SAS. All rights reserved.)

Objectives: Polymyxins are the last-line therapy for top-priority multidrug-resistant (MDR) gram-negative bacteria. However, polymyxin nephrotoxicity impedes its clinical application. This study aimed to design, synthesize, and identify a novel and promising polymyxin derivative with high efficacy and low toxicity., Methods: To design polymyxin derivatives, we reduced the hydrophobicity of the two hydrophobic domains (fatty acyl chain and D-Phe 6 -L-Leu 7 ) and modified the positive charged L-2,4-diaminobutyric acid (Dab) residues. Twenty-five derivatives were synthesized, and their antibacterial activities in vitro and renal cytotoxicities were determined. The nephrotoxicity and pharmacokinetic parameters of compound 12 were examined in rats. Antibacterial efficacy in vivo was evaluated using a mouse systemic infection model. Surface plasmon resonance analysis, compound 12-rifampicin combination therapy, and scanning electron microscopy were used to study the mechanism of action of compound 12., Results: This research found a new compound, identified as compound 12, which showed similar or increased antibacterial activity against all tested sensitive and carbapenem-resistant gram-negative bacteria. It exhibited reduced renal cytotoxicity and nephrotoxicity, a favorable pharmacokinetic profile, and maintained or improved antibacterial efficacy in vivo. Importantly, its anti-Pseudomonas aeruginosa activity significantly improved. Compound 12, when combined with rifampicin, enhanced the activity of rifampin against gram-negative bacteria. Compound 12 also showed a high affinity for lipopolysaccharide and disrupted cell membrane integrity., Conclusion: Reducing the hydrophobicity of the two domains reduced renal cytotoxicity and nephrotoxicity. Shortening the side chain of Dab 3 by one carbon maintained or increased its antibacterial activity both in vitro and in vivo. Furthermore, only the length of the side chain of Dab 9 could be shortened by one carbon among the Dab 1,5 and Dab 8,9 residues. The bactericidal effects of compound 12 were related to the disruption of cell membrane integrity. Compound 12 may be a promising candidate for combating sensitive and carbapenem-resistant gram-negative bacterial infections, especially Pseudomonas aeruginosa., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Masson SAS. All rights reserved.)

Antimicrobial resistance poses a significant threat to global health, necessitating the development of novel therapeutic agents with unique mechanisms of action. Inosine 5'-monophosphate dehydrogenase (IMPDH), an essential enzyme in guanine nucleotide biosynthesis, is a promising target for the discovery of new antimicrobial agents. High-throughput screening studies have previously identified several urea-based leads as potential inhibitors, although many of these are characterised by reduced chemical stability. In this work, we describe the design and synthesis of a series of heteroaryl-susbtituted analogues and the evaluation of their inhibitory potency against IMPDHs. Our screening targets ESKAPEE pathogens, including Pseudomonas aeruginosa, Staphylococcus aureus and Escherichia coli. Several analogues with submicromolar inhibitory potency are identified and show no inhibitory potency on human IMPDH nor cytotoxic effects on human cells. Kinetic studies revealed that these molecules act as noncompetitive inhibitors with respect to the substrates and ligand virtual docking simulations provided insights into the binding interactions at the interface of the NAD + and IMP binding sites on IMPDH., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Masson SAS.. All rights reserved.)

Antibiotic resistance has become a serious threat to public health, thus novel antibiotics are urgently needed to combat drug-resistant bacteria including methicillin-resistant Staphylococcus aureus (MRSA). The 1,4-dicarbonylthiosemicarbazide is an interesting chemotype that could exhibit antibacterial activity. However, the currently available compounds are not as potent as clinical antibiotics. Herein, we adopted the computer-aided drug design strategy, substructure search, to retrieve antibacterial 1,4-dicarbonylthiosemicarbazide derivatives, and identified compound B5 (Specs ID: AG-690/15432331) from the Specs chemical library that exhibited moderate activity (minimum inhibitory concentration (MIC): 6.25 μg/mL) against Staphylococcus aureus ATCC 29213. Based on that compound, we further designed and synthesized 45 derivatives, and evaluated their antibacterial activity. Eight derivatives were more potent than or equivalent to vancomycin (MIC: 1.56 μg/mL). We compared the three most potent ones for their cytotoxicity to HepG2 and HUVEC cells and selected compound 1b as our lead compound for comprehensive biological evaluation. As a result, compound 1b exhibited a bacteriostatic mode, and was active against a panel of Gram-positive bacteria strains, metabolically stable, and effective to protect the mice from MRSA infection. More importantly, we applied 2D similarity calculation and reverse docking to predict potential targets of compound 1b. Through experimental validation and molecular dynamics simulation, we were able to confirm that compound 1b inhibited Staphylococcus aureus DNA gyrase (IC 50 : 1.81 μM) and DNA supercoiling, potentially by binding to the ATPase domain, where ASP81, GLU58 and GLN91 formed key hydrogen bonds. Taken together, we have discovered a new class of DNA gyrase inhibitors represented by compound 1b for the treatment of MRSA infection, through the design, synthesis, and biological evaluation of novel 1,4-dicarbonylthiosemicarbazides., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. The Institute of Materia Medica, Chinese Academy of Medical Sciences has filed and been granted a patent that covers compound 1b (Patent Number: ZL201810091202. X)., (Copyright © 2024 Elsevier Masson SAS. All rights reserved.)

Developing multifunctional materials which could simultaneously possess anti-bacterial ability and electromagnetic (EM) absorption ability during medical care is quite essential since the EM waves radiation and antibiotic-resistant bacteria are threatening people's health. In this work, the multifunctional carbon fiber/Ti 3 C 2 T x MXene (CM) were synthesized through repeated dip-coating and following in-situ growth method. The as-fabricated CF/MXene displayed outstanding EM wave absorption and highly efficient photothermal converting ability. The minimum reflection loss (RL) of -57.07 dB and ultra-broad absorption of 7.74 GHz could be achieved for CM composites. By growth of CoNi-layered double hydroxides (LDHs) sheets onto MXene, the absorption bandwidth for carbon fiber/Ti 3 C 2 T x MXene layered double hydroxides (CML) could be reach 5.44 GHz, which could cover the whole Ku band. The excellent photothermal effect endow the CM composites with excellent antibacterial performance. The antibacterials tests indicated that nearly 100 % bactericidal efficiency against E. acoil and S. aureus was obtained for the CM composite after exposure to near-infrared region (NIR) irradiation. This work provides a promising candidate to combat medical device-related infections and EM pollution., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

LpxC inhibitors are new-type antibacterial agents developed in the last twenty years, mainly against Gram-negative bacteria infections. To enable the development of novel LpxC inhibitors with potent antibacterial activities, several series of compounds were designed and synthesized and their antibacterial activities were evaluated against E. coli ATCC25922, P. aeruginosa ATCC27853, P. aeruginosa clinical isolate PAE 22-1, K. pneumoniae ATCC700603, K. pneumoniae clinical isolate KPN + 22-1 in vitro. Compound 6i exhibited significant antibacterial activities against above five Gram-negative bacteria except P. aeruginosa ATCC27853. Moreover, compound 6i exhibited moderate liver microsomal stability and a promising pharmacokinetic profile (AUC 0-t  = 1050 ng h mL -1 , oral bioavailability of 13.3 %) in Sprague-Dawley rats, acceptable PPB, low risk of drug-drug interactions and non-cytotoxic activity against hepatic cell. Collectively, compound 6i could be a promising Gram-negative antibacterial agent for further investigation., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Masson SAS. All rights reserved.)

The widespread emergence of antibiotic resistance poses a substantial challenge to global health. While polymyxin E serves as a final option in treatment, its effectiveness is hindered by dose-related toxicity. A crucial strategy for addressing this issue involves incorporating an antibiotic adjuvant to enhance the antibiotic's efficacy and decrease the required dosage. Here, we reported a multifunctional antibacterial compound A33, containing a 2-aminothiazole scaffold. In vitro studies demonstrated that A33 in combination with polymyxin E inhibited the growth of various Gram-negative bacteria, meanwhile with minimum inhibitory concentrations (MICs) of 0.5-4 μg/mL against twenty-three Gram-positive bacteria, including two drug-resistant strains. In vivo studies showed significant efficacy of the combined treatment of A33 and polymyxin E in a mouse infection model. The mice treated with compound A33 (64 mg/kg) and polymyxin E (0.5 mg/kg) in combination had a 100 % survival rate. Mechanistic studies suggested that A33 might exert its synergistic effect by targeting the outer membrane of Gram-negative bacteria. The ADMET data demonstrated that A33 possessed good pharmacokinetic profiles and drug-likeness properties. Overall, the optimized compound A33 assisted polymyxin E in combating various Gram-negative bacteria and exhibited bactericidal effects against drug-resistant Gram-positive bacteria, offering a new potential therapeutic approach for managing mixed bacterial infections., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Masson SAS. All rights reserved.)

Inhibition of quorum sensing (QS) is an impending approach for targeting bacterial infection. Fourteen benzo[d]thiazole and 2-pyrazolo[1,5-a]pyrimidin-3-yl)benzo[d]thiazoles analogues were designed and synthesized as promising LasR antagonists with QS inhibition activity. Among the investigated compounds, compounds 3c, 3e, and 8d exhibited the highest percentage inhibition in biofilm formation (77 %, 63.9 %, 69.4 %), pyocyanin production (74.6 %, 64.9, 69.4 %), and rhamnolipids production (58.5 %, 51 %, 54.3 %) in P. aeruginosa, respectively. Additionally, compounds 3c, 3e and 8d achieved IC 50 values against Las R equal 1.37 ± 0.35, 1.55 ± 0.24, 1.1 ± 0.15 μM respectively. Also, molecular docking of the target compounds into the LasR binding site co-crystalized "odDHL" revealed their binding with the essential residues for protein inhibition. Additionally, molecular dynamics simulation (MDS) experiments over 200 ns of compound 3c showed its ability to interact with the LasR binding site with dissociation of the protein's dimer confirming its action as a LasR antagonist. The obtained findings inspire further investigation for benzo[d]thiazole and 2-pyrazolo[1,5-a]pyrimidin-3-yl)benzo[d]thiazoles aiming to design and synthesize more potential QS inhibitors., Competing Interests: Declaration of competing interest There are no interests to declare., (Copyright © 2024 Elsevier Masson SAS. All rights reserved.)

Methicillin-resistant Staphylococcus aureus (MRSA) has emerged as a major pathogen causing infections in hospitals and the community, and there is an urgent need for the development of novel antibacterials to combat MRSA infections. Herein, a series of amphiphilic honokiol derivatives containing an oxazolethione moiety were prepared and evaluated for their in vitro antibacterial and hemolytic activities. The screened optimal derivative, I3, exhibited potent in vitro antibacterial activity against S. aureus and clinical MRSA isolates with MIC values of 2-4 μg/mL, which was superior to vancomycin in terms of its rapid bactericidal properties and was less susceptible to the development of resistance. The SARs analysis indicated that amphiphilic honokiol derivatives with fluorine substituents had better antibacterial activity than those with chlorine and bromine substituents. In vitro and in vivo toxicity studies revealed that I3 has relatively low toxicity. In a MRSA-infected mouse skin abscess model, I3 (5 mg/kg) effectively killed MRSA at the infected site and attenuated the inflammation effects, comparable to vancomycin. In a MRSA-infected mouse sepsis model, I3 (12 mg/kg) was found to significantly reduce the bacterial load in infected mice and increase survival of infected mice. Mechanistic studies indicated that I3 has membrane targeting properties and can interact with phosphatidylglycerol (PG) and cardiolipin (CL) of MRSA cell membranes, thereby disrupting MRSA cell membranes, further inducing the increase of reactive oxygen species (ROS), protein and DNA leakage to achieve rapid bactericidal effects. Finally, we hope that I3 is a potential candidate molecule for the development of antibiotics to conquer superbacteria-related infections., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Masson SAS. All rights reserved.)

Nitrofuran antibiotics (NFAs) residues in waterare a persistent concern for the public due to the potential threats they pose to human health and the environment. Therefore, efficient probes that are capable of detecting trace amounts of antibiotics in real water environments have become a top priority. Herein, a novel fluorescent Zn-MOF probe (MOF-1) was revealed for the highly selective and sensitive sensing of NFAs. MOF-1 was rationally constructed with Zn(NO 3 ) 2 ·6H 2 O, 5,5'-(anthracene-9,10-diyl) diisophthalic acid (H 4 ADIP) and 1,3-bis(imidazol-1-ylmethyl)-benzene (mbib) by using the solvothermal method. Fluorescence sensing experiments demonstrate that MOF-1 can function as a fluorescent sensor for selective, sensitive, and rapid detection of NFAs among 15 antibiotics including ciprofloxacin (CPFX), chloramphenicol (CAP), sulfonamides and NFAs. Fluorescence titration experiments indicated that MOF-1 exhibited remarkably low detection limits of 0.19 μM, 0.26 μM, and 0.34 μM for furazolidone (FZD), furaltadone (FDH) and nitrofurazone (NFZ), respectively. Meanwhile, MOF-1 was successfully employed for NFAs detection in real samples with the recoveries of 98.7 % - 104.1 %, and a relative standard deviation below 5.1 %. Moreover, the sensing mechanism could be ascribed to the synergistic effect between the internal filtering effect and photoinduced electron transfer according to the experiment results and DFT calculations. Additionally, test strips were prepared based on MOF-1 for point of care testing of NFAs., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Chitosan derivatives, including O-carboxymethyl chitosan (CMC), N-(2-hydroxypropyltrimonium chloride)-O-carboxymethyl chitosan (QCMC), and N-(2-hydroxypropyltrimonium chloride)-O-dodecylylpyridine chitosan quaternary ammonium salt (DQCMC), were synthesized and characterized using Fourier transform infrared (FTIR) spectroscopy, 1 H nuclear magnetic resonance ( 1 H NMR) spectroscopy, Ultraviolet-visible (UV-vis) spectroscopy, and element analysis (EA). The antibacterial activities of chitosan and chitosan derivatives against Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus) were evaluated through the minimum inhibitory concentration (MIC), minimum bactericidal concentration (MBC), and antibacterial rate assays. Results demonstrated that DQCMC exhibited significantly higher antibacterial efficacy compared to chitosan, CMC, and QCMC. The MIC of DQCMC against E. coli and S. aureus were 31 μg/mL and 7 μg/mL, respectively, with a 100 % antibacterial rate at a concentration of 0.5 mg/mL. Furthermore, assessment of mouse fibroblast (L929) cell viability using cell counting kit-8 (CCK-8) methods revealed no toxicity associated with the material., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Developing pure diastereoisomeric molecular hybrids for the selective inhibition of bacterial growth opened new avenues for combating the ever-increasing microbial resistance. Considering this, a series of diastereoisomeric pure pyrazolyl-dihydrofurans (7a-7y) were synthesized and characterized using NMR, LCMS, and X-ray crystallography. DFT based method was used to explore the configurational stability of cis over trans isomeric form. Considering 7a and 8a as representative isomeric forms with same structural framework, the difference in their bio-efficacy against bacterial and fungal strains was assessed using serial dilution method. The relatively high inhibition of bacterial growth by the cis isomeric form (7a) (MIC = 1.562 µg/mL), amoxicillin (MIC = 3.125 µg/mL) inspired us to broaden the substrate scope for synthesizing a series of pure diastereoisomeric cis forms as selective anti-bacterial agents. However, both the isomers displayed antifungal activity less than the standard drug (Fluconazole) employed in the study. All the reactions proceeded smoothly and yielded a diverse array of dihydrofuran derivatives. The developed synthetics were found to be non-cytotoxic against mouse fibroblast cells and didn't affect the seed germination of Brassica nigra seeds when treated at 1 mg/mL concentration. The experimentally determined in vitro results were further validated using in silico molecular docking and dynamics studies., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)

Antisense oligonucleotides have been developed as therapeutic compounds, with peptide nucleic acid (PNA) emerging as a promising nucleic acid mimic for antimicrobial applications. To be effective, PNAs must be internalized into bacterial cells, as they are not naturally absorbed. A strategy to improve PNA membrane penetration and cellular uptake involves covalently conjugating them to cell-penetrating peptides. However, these membrane-active peptides can exhibit cytotoxicity, and their efficiency as PNA carriers needs to be enhanced. Therefore, we explored new peptide-PNA conjugates and their linkers to understand how they affect PNA uptake into bacteria. We conjugated PNA to two peptides, anoplin and (KFF) 3 K, along with their structurally stabilized hydrocarbon-stapled derivatives, and evaluated their transport into various bacterial strains. The PNA sequence targeted bacterial mRNA encoding the essential acyl carrier protein. As linkages, we used either a non-cleavable 8-amino-2,6-dioxaoctanoyl (ethylene glycol, eg1) linker or a reducible disulfide bridge. We found that the hydrocarbon-stapled peptides did not enhance PNA delivery, despite the strong inner- and outer-membrane-penetrating capabilities of the standalone peptides. Additionally, the disulfide bridge linkage, which is cleavable in the bacterial cytoplasm, decreased the antimicrobial activity of the peptide-PNA conjugates. Notably, we identified anoplin as a new potent PNA carrier peptide, with the anoplin-eg1-PNA conjugate demonstrating antibacterial activity against E. coli and S. Typhimurium strains in the 2-4 µM range., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

The paenilamicins are a group of hybrid nonribosomal peptide-polyketide compounds produced by the honey bee pathogen Paenibacillus larvae that display activity against Gram-positive pathogens, such as Staphylococcus aureus. While paenilamicins have been shown to inhibit protein synthesis, their mechanism of action has remained unclear. Here we determine structures of paenilamicin PamB2-stalled ribosomes, revealing a unique binding site on the small 30S subunit located between the A- and P-site transfer RNAs (tRNAs). In addition to providing a precise description of interactions of PamB2 with the ribosome, the structures also rationalize the resistance mechanisms used by P. larvae. We further demonstrate that PamB2 interferes with the translocation of messenger RNA and tRNAs through the ribosome during translation elongation, and that this inhibitory activity is influenced by the presence of modifications at position 37 of the A-site tRNA. Collectively, our study defines the paenilamicins as a class of context-specific translocation inhibitors., Competing Interests: Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

The zoonosis caused by Nocardia is increasing seriously. But commonly used antibiotic drugs often lead to resistance. N. seriolae dUTPase ( Ns dUTPase) plays a key role in the proliferation of Nocardia , and was regarded as a potent drug target. However, there was little report about the Ns dUTPase inhibitors. In this study, we discovered a series of novel Ns dUTPase inhibitors to fight against Nocardia . The first crystal structure of Ns dUTPase was released, and a structure-based computational design was performed. Compounds 4b and 12b exhibited promising activities towards Ns dUTPase (IC 50  = 0.99 μM and 0.7 μM). In addition, they showed satisfied anti- Nocardia activity (MIC value ranges from 0.5 to 2 mg/L) and low cytotoxicity, which were better than approved drugs oxytetracycline and florfenicol. Molecular modelling study indicated that hydrophobic interaction might be the main contribution for ligand binding. Our results suggested that Ns dUTPase inhibitors might be a useful way to repress Nocardia .

Among the most important aquaculture resources for our country, salmon and trout stand out. Their production has increased significantly in recent decades, making them two of the most valuable resources in economic terms. However, high aquaculture production has allowed many pathogens to proliferate, causing infectious diseases and significant production losses. Piscirickettsia salmonis is a gram-negative, facultative intracellular bacterium that is responsible for causing severe disease in a variety of salmonid fish species. Despite the significant impact of P. salmonis on aquaculture, effective treatments for this disease remain limited. Current prevention and control strategies often include antibiotics and vaccines. However, these treatments have shown varying degrees of efficacy. A promising approach involves synthesizing bioactive analog compounds with antibacterial properties. Quinones, secondary metabolites that are abundant in nature, have become a focal point of interest due to their diverse physiological activities, including antibiotic, insecticidal, antifungal, and anticancer properties. In this study, it is shown the synthesis of series 6-bromo-7-arylaminoisoquinoline-5,8-quinones, the characterization of these compounds using classical spectroscopic methods such as one-dimensional nuclear magnetic resonance (NMR), FT-IR (infrared), mass spectrometry, and the biological activity against Piscirickettsia salmonis. The brominated derivative compounds showed no cytotoxicity at any concentration evaluated. Furthermore, the infectivity of P. salmonis after treatment with the analog compounds indicated that derivatives methyl 6-bromo-7-((4-methoxyphenyl)amino)-1,3-dimethy-5,8-dioxo-5,8-dihydroisoquinoline-4-carboxylate (4b) and methyl 7-((4'-amino-[1,1'-biphenyl]-4-yl)amino)-6-bromo-1,3-dimethy-5,8-dioxo-5,8-dihydroisoquinoline-4-carboxylate (4g) reduced the bacterial load at 25 μg/mL concentration., (© 2024 John Wiley & Sons Ltd.)

Green-synthesized silver and copper nanoparticles (NPs), along with their composites, exhibit various biological activities. Ocimum sanctum (Holy basil), traditionally used as medicine in South Asia, treats respiratory disorders, digestive issues, skin diseases and inflammatory conditions. Modern scientific studies support these bioactivities; however, no studies have investigated their bioactivity in combination with NPs. In this study, silver and copper NPs were synthesized using AgNO 3 and CuSO 4 ·5H 2 O solutions, respectively, with Ocimum sanctum leaf extract, and their antibacterial, antioxidant and anticancer properties were examined. Spectroscopic analyses, including Fourier transform infra-red (FTIR), transmission electron microscopy (TEM) and X-ray diffraction (XRD), elucidated the physicochemical characteristics of the green-synthesized nanoparticles ( Os -AgNPs and Os -CuNPs), revealing sizes of 11.7 and 13.1 nm, respectively. The Os -AgNPs: Os -CuNPs nano-composite with a 1:2 ratio exhibited a zone of inhibition ranging from 8 to 12 mm against tested bacterial pathogens. Additionally, the NPs and their composites demonstrated potent antioxidant activity, with notable 2-diphenyl-2-picrylhydrazyl (DPPH) scavenging activity observed in composites with ratios of 2:1 and 1:2. Furthermore, they displayed potential anticancer activity against human leukaemia (Jurkat) cancer cells. Although no distinct difference in anticancer property was observed among the NPs and their composites, our study highlights their well-defined nanostructure and significant biological activity, suggesting their potential as therapeutic agents in the pharmaceutical industry.

This study focuses on the activity of previously reported imine and β-lactam derivatives against methicillin-resistant Staphylococcus aureus (MRSA) isolates. The presence of mecA and blaZ genes in the isolates was determined, and the minimum inhibitory concentration (MIC) values were determined based on the antibacterial activity against these isolates. Active compounds were selected and their ability to act against resistant isolates in vitro was determined. Concurrently, biochemical (nitrocefin) and molecular (qRT-PCR) tests were used to investigate the ability of the compounds to induce resistance genes in MRSA isolates. The cytotoxicity of the compounds on human dermal fibroblasts (HDF) was investigated. The MIC values of compounds (10) and (12) against MSSA and MRSA isolates were 7.81 and 15.62 μg ml -1 , respectively. The most active compounds were identified as (10) and (12), and it was observed that the isolates did not develop resistance to these compounds in vitro. These compounds were found to inhibit β-lactamase, reduce the expression of resistance genes, and exhibit reduced HDF cell toxicity in a dose-dependent manner. According to the findings of the study, it can be concluded that these compounds show promise as hits with an interesting mechanism of action for further chemical modifications to develop new MRSA inhibitors., Competing Interests: Compliance with ethical standards. Conflict of interest: The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to the Japan Antibiotics Research Association.)

This study uses the aerial parts of Panicum maximum total extract (PMTE) to synthesize silver nanoparticles (AgNPs) in an environmentally friendly manner. TEM, SEM, FTIR, X-ray powder diffraction (XRD), Zeta potential, UV, and FTIR were used to characterize the green silver nanoparticles (PM-AgNPs). PM-AgNPs were evaluated as anticancer agents compared to (PMTE) against breast (MCF-7), lung (A549), and ovary adenocarcinoma (SKOV3) human tumour cells. The antibacterial activity of AgNPs was assessed against Staphylococcus aureus isolates. The PM-AgNPs had an absorbance of 418 nm, particle size of 15.18 nm, and zeta potential of -22.4 mV, ensuring the nanosilver's stability. XRD evaluated the crystallography nature of the formed PM-AgNPs. The cytotoxic properties of PM-AgNPs on MCF-7 and SKOV 3 were the strongest, with IC50s of 0.13 ± 0.015 and 3.5 ± 0.5 g/ml, respectively, as compared to A549 (13 ± 3.2 µg/mL). The increase in the apoptotic cells was 97.79 ± 1.61 and 96.6 ± 1.91% for MCF-7 and SKOV3 cell lines, respectively. PM-AgNPs were found to affect the membrane integrity and membrane permeability of 50 and 43.75% of the tested isolates, respectively. Also, PM-AgNPs have recorded a reduction in the biofilm formation of S. aurues . These results suggest using PM-AgNPs to treat breast and ovarian cancers.

The current therapies against gastric pathogen Helicobacter pylori are ineffective in over 20% of patients. Enzymes belonging to the purine salvage pathway are considered as novel drug targets in this pathogen. Therefore, the main aim of the current study was to determine the antibacterial activity of pyridoxal 5'-phosphate (PLP), an active form of vitamin B6, against reference and clinical strains of H. pylori . Using a broad set of microbiological, physicochemical (UV absorption, LC-MS, X-ray analysis) and in silico experiments, we were able to prove that PLP inhibits adenylosuccinate synthetase (AdSS) from H. pylori by the competition with GTP (IC 50 eq ∼30 nM). This behaviour was attributed to formation of a Schiff base with a lysine residue (a covalent bond with Lys322 in the GTP binding site of AdSS) and was potentiated by the presence of vitamin C. This antibacterial activity of PLP gives hope for its future use against H. pylori .

Background: The threats to the safety of humans and the environment and the resistance of agricultural chemicals to plant pathogenic fungi and bacteria highlight an urgent need to find safe and efficient alternatives to chemical fungicides and bactericides. In this study, a series of Berberine (BBR) derivatives were designed, synthesized and evaluated for in vitro and in vivo antimicrobial activity against plant pathogenic fungi and bacteria., Results: Bioassay results indicated that compounds A11, A14, A20, A21, A22, A25, A26, E1, E2, E3, Z1 and Z2 showed high inhibitory activity against Sclerotinia sclerotiorum and Botrytis cinerea. Especially, A25 showed a broad spectrum and the highest antifungal activity among these compounds. Its EC 50 value against Botrytis cinerea was 1.34 μg mL -1 . Compound E6 possessed high inhibitory activity against Xanthomonas oryzae and Xanthomonas Campestris, with MIC 90 values of 3.12 μg mL -1 and 1.56 μg mL -1 . A Topomer CoMFA model was generated for 3D-QSAR studies based on anti-B. cinerea effects, with high predictive accuracy, showed that the addition of an appropriate substituent group at the para-position of benzyl of BBR derivatives could effectively improve the anti-B. cinerea activity. In addition, compound A25 could significantly inhibit the spore germination of Botrytis cinerea at low concentration, and compound F4 exhibited remarkable curative and protective efficiencies on rice bacterial leaf blight., Conclusion: This study indicates that the BBR derivatives are hopeful for further exploration as the lead compound with novel antimicrobial agents. © 2024 Society of Chemical Industry., (© 2024 Society of Chemical Industry.)

Diabetes is a serious metabolic disorder characterized by abnormal glucose levels in the body. Delayed wound healing is a severe diabetes complication. Nanotechnology represents the latest advancement in treating diabetic wounds through nanoparticles (NPs). In this study, silver nanoparticles (AgNPs) were synthesized using a green method involving cucumber pulp extract. The synthesis was confirmed using techniques including ultraviolet-visible spectrophotometry (UV-Vis), Fourier-transform infrared spectroscopy (FT-IR), X-ray diffraction (XRD), scanning electron microscopy (SEM), and energy dispersive X-ray (EDX). To evaluate wound-healing properties, mouse models were utilized with wounds induced by excision on the dorsal surface. An ointment containing silver nanoparticles was applied to assess its healing potential. Additionally, antibacterial and antioxidant activities were examined using agar well diffusion and DPPH scavenging methods, respectively. The results demonstrated that the ointment prepared with green synthesized AgNPs effectively healed the wounds within 15 days, while also exhibiting antibacterial and antioxidant properties. Therefore, it can be concluded that due to its efficacy in biological activities, silver nanoparticles can be employed in the treatment of diabetic wounds., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

A novel antibacterial film based on arabinoxylan (AX) was prepared by introducing ferulic acid (FA) to AX through a laccase-catalyzed procedure. The ferulic acid-arabinoxylan conjugates (FA-AX conjugates) have been characterized. Results showed that FA was successfully grafted onto the AX chains by covalent linkages, likely through nucleophilic addition between O-Ph in the phenolic hydroxyl group of FA, or through Michael addition via O-quinone intermediates. FA-AX conjugates showed improved crystallinity, thermal stability, and rheological properties, as well as a distinct surface morphology, compared with those of native AX. Moreover, FA-AX conjugates exhibited enhanced antibacterial ability against Staphylococcus aureus, Escherichia coli, Shewanella sp., and Pseudomonas sp. Mechanistic studies revealed that the enhanced antibacterial ability was due to the penetration of bacterial membrane by the phenolic molecule and the steric effect of FA-AX conjugates. The study demonstrates that the laccase-induced grafting method was effective in producing FA-AX conjugates; we have demonstrated its antibacterial ability and great potential in prolonging the shelf life of fresh seafood products., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)

Antimicrobial resistance (AMR) is a pressing global issue exacerbated by the abuse of antibiotics and the formation of bacterial biofilms, which cause up to 80% of human bacterial infections. This study presents a computational strategy to address AMR by developing three novel quantitative structure-activity relationship (QSAR) models based on molecular topology to identify potential anti-biofilm and antibacterial agents. The models aim to determine the chemo-topological pattern of Gram (+) antibacterial, Gram (-) antibacterial, and biofilm formation inhibition activity. The models were applied to the virtual screening of a commercial chemical database, resulting in the selection of 58 compounds. Subsequent in vitro assays showed that three of these compounds exhibited the most promising antibacterial activity, with potential applications in enhancing food and medical device safety.

This study refers to the intricate world of Acinetobacter baumannii , a resilient pathogenic bacterium notorious for its propensity at antibiotic resistance in nosocomial infections. Expanding upon previous findings that emphasised the bifunctional enzyme PaaY, revealing unexpected γ-carbonic anhydrase (CA) activity, our research focuses on a different class of CA identified within the A. baumannii genome, the β-CA, designated as 𝛽-AbauCA (also indicated as CanB), which plays a crucial role in the resistance mechanism mediated by AmpC beta-lactamase. Here, we cloned, expressed, and purified the recombinant 𝛽-AbauCA, unveiling its distinctive kinetic properties and inhibition profile with inorganic anions (classical CA inhibitors). The exploration of 𝛽-AbauCA not only enhances our understanding of the CA repertoire of A. baumannii but also establishes a foundation for targeted therapeutic interventions against this resilient pathogen, promising advancements in combating its adaptability and antibiotic resistance.

Overuse of antibiotics and the widespread environmental accumulation of antibiotics drive the evolution and spread of antimicrobial resistance, posing a significant global health threat by reducing the effectiveness of available treatments and increasing the risk of untreatable infections. We designed and synthesized PhoPS, a novel photocaged β-lactamase inhibitor, which incorporates the pharmacophore of sulbactam caged with a photoresponsive moiety of o -nitrobiphenyl derivative. Experimental results demonstrate its rapid photoactivation, good stability in solution, and light-activated β-lactamase inhibition in vitro. PhoPS displays synergy with a cephalosporin antibiotic cefoperazone against both susceptible and resistant strains of Escherichia coli and biofilm formation. Additionally, PhoPS treatment demonstrates the potential to suppress the development of resistance in E. coli . These findings suggest that PhoPS offers a promising approach for restoring the efficacy of existing antibiotics and mitigating the emergence of AMR.

Vancomycin and norvancomycin have diminished antibacterial efficacy due to acquired or intrinsic resistance from mutations in the terminal dipeptide of lipid II in Gram-positive bacteria or failure to penetrate into the periplasm in Gram-negative bacteria. Herein, we rationally designed and synthesized a series of vancomycin analogues bearing single amine or guanidine functionality, altering various linkers and modification sites, to combat the resistance. Extensive antibacterial screening was performed to delineate a comprehensive SAR. Many derivatives revitalized the activity in vitro, exhibiting a 4-128-fold or 2-16-fold enhancement against the acquired or intrinsic resistance with lower toxicity. Significantly, the optimal compound 4g demonstrated greater pharmacokinetic and pharmacodynamic profiles. Further studies uncovered additional independent and synergistic mechanisms for 4g , including the enhanced membrane activity and augmented inhibition of peptidoglycan biosynthesis via increased lipid II binding, highlighting its potential as a future lead candidate to replenish the glycopeptide antibiotic arsenal.

Organic ferroelectrics show great applications in the fields of biomedicine, including disease treatment, biosensors, and tissue engineering. Organosilicon pharmaceutical intermediates generally include chiral centers and have satisfying biosafety, biocompatibility, or even biodegradability, which provide versatile platforms for the design of ferroelectricity. However, their academic values in ferroelectricity have long been long overlooked. Here, we demonstrated the ferroelectric properties of 4-acetoxy-azacyclic butanone (4-AA), a key synthetic organosilicon-based intermediate of carbapenem drugs. This compound undergoes a 222F2-type ferroelectric-ferroelastic phase transition at 326 K. As an organic piezoelectric material, 4-AA can produce reactive oxygen species when subjected to ultrasonic vibrations. Combined with its desirable biocompatibility, this material may contribute to antimicrobial and wound healing, tumor treatment, etc. This work will provide inspiration for the discovery of multifunctional biomedical ferroelectric materials as well as their related application prospects.

Nanotechnology has been a central focus of scientific investigation over the past decades owing to its versatile applications. The synthesis of silver nanoparticles (AgNPs) through plant secondary metabolites is a cost-effective and eco-friendly approach. The present study employed Brassica carinata microgreen extracts (BCME) to promote the reduction of silver nitrate (AgNO 3 ) salt into Brassica carinata microgreen silver nanoparticles (BCM-AgNPs). The physicochemical properties of the biosynthesized AgNPs were characterized through both spectroscopy and microscopy techniques. Furthermore, the antimicrobial property of the biosynthesized AgNPs was assessed against six selected pathogenic microorganisms, and finally, their safety was evaluated on a normal Vero cell line through an MTT cytotoxicity assay. The UV-visible spectrum revealed that BCM-AgNPs exhibited an absorption peak at 420 nm. The potential functional groups involved in the biosynthesis of AgNPs were identified by Fourier transform infrared (FTIR) analysis. Scanning electron microscopy (SEM) revealed a spherical nature of the biosynthesized AgNPs. Transmission electron microscopy (TEM) analysis revealed the crystallinity of the AgNPs, averaging 34.68 nm in size. X-ray diffraction (XRD) investigation further confirmed the crystalline structure of the AgNPs. The zeta potential exhibited a significant value of - 22.5 ± 1.16 mV. Regarding the antimicrobial potential, BCM-AgNPs exhibited promising antimicrobial activity against the tested pathogens, with a minimum inhibitory concentration (MIC) of 62.5 µg/mL observed in Pseudomonas aeruginosa. Further cytotoxicity assessment of BCM-AgNPs conducted on Vero cells demonstrated their safety. This study presents a novel approach to synthesizing AgNPs using a nutraceutical microgreen, offering a biocompatible and promising alternative for combating multi-drug resistance., Competing Interests: Declarations. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Hydroxyapatite is one of the most widely used materials in biomedical applications in reparative and regenerative medicine. Doping of nanosized hydroxyapatite improves its bioactive properties, and thus, the synthesis of different types of nanohydroxyapatite with antimicrobial activity is a perspective route of modern materials science. In this study, undoped hydroxyapatite (HAp), hydroxyapatite doped with silver (HAp with 0.1, 0.5 and 1 mol% Ag + ions), and silicate-substituted hydroxyapatite doped with silver (Si-HAp with 0.1, 0.5 and 1 mol% Ag + ions) nanoparticles (NPs) were synthesized by microwave-assisted hydrothermal technique and sintered at 450 °C. The structural properties and composition of obtained hydroxyapatite NPs were investigated using X-ray powder diffraction (XRPD), Fourier-transformed infrared spectroscopy (FT-IR), and Energy-dispersive X-ray spectroscopy (EDS). The morphology of synthesized nanosized powders was detected using the high-resolution transmission electron microscopy (HRTEM) technique. The results of XRPD for all synthesized nanosized powders confirmed the presence of hydroxyapatite crystal structure. The FT-IR spectra confirmed the presence of functional groups characteristic of the hydroxyapatite structure. The EDS analysis of obtained materials has shown the presence of Ca, P, O, Si, and Ag elements. Significant differences in size and morphology of the obtained particles were found using HRTEM. The particles have an elongated, rod-like shape with subtle differences. Moreover, HAp doped with 1 mol% Ag + ions and Si-HAp doped with 1 mol% Ag + ions nanosized powders showed antibacterial activity in comparison to pure hydroxyapatite both against gram-positive and gram-negative bacterial strains (Klebsiella pneumoniae, Pseudomonas aeruginosa, Staphylococcus epidermidis, Staphylococcus aureus, Enterococcus faecalis). These two types of hydroxyapatite NPs also demonstrated antifungal activity against reference strains of Candida albicans, Candida kruzei, and Candida tropicalis, with stronger activity observed for Si-HAp doped with silver., Competing Interests: Declarations. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

As a broad-spectrum antimicrobial material, ZnO nanoparticles (NPs) offer a novel approach to infected wounds in the clinic; however, it is very necessary to improve the antimicrobial performance of ZnO to satisfy the clinic requirements. In this work, a new antimicrobial hybrid ZnO@PDA/GL13K was prepared by attaching the antimicrobial GL13K peptide on the surface of ZnO NPs via polydopamine (PDA) as a covalent bonding agent, which can enhance the reactive oxygen species (ROS) production and damage the cell wall, showing superior antimicrobial efficacy. Besides, the ZnO@PDA/GL13K hybrid can promote the healing of bacterial infected wounds, with the wound area only remaining 1.8% on day 9, about 2 times smaller than that of the ZnO group. Moreover, ZnO@PDA/GL13K also showed good biocompatibility, and no side effect on normal tissue and organs was found, implying that the antimicrobial hybrid may possess prospective application in biomedical fields.

The accumulation of agricultural and industrial residues inevitably contributes to environmental pollution. Thus, several scientific investigations have been conducted to overcome this problem and to add an economic value proposition. Unlike typical sugarcane bagasse applications, this work presents a novel application of sugarcane bagasse waste in a green synthesis approach for forming zinc oxide nanoparticles (ZnO-NPs). This work opens the door to studying the potential of sugarcane bagasse in a green synthesis orientation. Phytochemical assessment of the aqueous extract of sugarcane bagasse waste was conducted by studying total flavonoid content, total phenolic content, and antioxidant assays. ZnO-NPs were synthesized using the aqueous sugarcane bagasse extract (ASCBE) with a 96% yield. To obtain 99.7% pure ZnO-NPs, nanoparticles were calcined at 550 °C to remove any remaining plant extract residues. The purity and yield of the produced and modified ZnO-NPs were studied. The initially produced and modified ZnO-NPs were characterized using XRD, FT-IR, UV, TEM, TGA, and PL and to determine the necessity of the calcination step. A detailed proposed mechanism for the formation of ZnO-NPs mediated by ASCBE was introduced. The ZnO-NPs were studied for their antibacterial, antifungal, and antiviral activities. The ZnO-NPs before calcination were found to exhibit more potent antimicrobial activity against both P. aeruginosa and A. niger compared to the calcined ZnO-NPs. In addition, molecular docking analysis revealed that the ZnO-NPs had the strongest binding affinity towards the P. aeruginosa RhlG/NADP active-site complex and the crystal structure of Actibind, a T2 RNase of A. Niger . ZnO-NPs also showed promising binding interactions with viral targets, including the Herpes simplex virus type II protease and Influenza virus NS1 effector domain. Additionally, environmental and economic studies were achieved to relate the scientific study with daily life applications.

We report the synthesis of the antimicrobial cyclodepsipeptides marformycin A ( 1 ) and marformycin D ( 2 ) using a solid-phase approach. A scalable solution-phase synthesis of the γ-hydroxypiperazic acid subunit in 2 , starting from cis -hydroxyproline, is also described. Structural analysis of 1 and its Leu- epi congener demonstrates conformational differences that may underlie their divergent antimicrobial activities. The described approach enables further development of conformation-activity relationships within this class of depsipeptide natural products.

Opantimycin A, a rare antimycin-class antibiotic without the macrolide core, was isolated from Streptomyces sp. RK88-1355 in 2017. In this study, we explored the total synthesis and stereochemical assignment of opantimycin A. The synthesis of all potential diastereomers has been accomplished via traceless Staudinger ligation. A comparison of the spectroscopic data of the synthesized compounds with that reported for the natural product confirmed that the absolute configuration of the natural product was (14 S ,17 R ,21 R ). Two analogous compounds were prepared, where the Dhb (( Z )-dehydrobutyrine) moiety was replaced with Dha (dehydroalanine) or ΔVal moieties, respectively. The inhibitory activities of these synthetic compounds against the production of the anti-inflammatory cytokine IL-6 were evaluated, and two potential candidates for further development as anti-inflammatory agents were identified.

The rapid rise of antibiotic resistance calls for the discovery of new antibiotics with distinct antibacterial mechanisms. New target mining is indispensable for developing antibiotics. Plant-microbial antibiotics are appealing to underexplored sources due to a dearth of comprehensive understanding of antibacterial activity and the excavation of new targets. Here, a series of phloroglucinol derivatives of plant-root-associated Pseudomonas fluorescens were synthesized for structure-activity relationship analysis. Notably, 2,4-diproylphloroglucinol (DPPG) displayed efficient bactericidal activity against a wide range of gram-positive bacteria. Importantly, mechanistic study exhibits that DPPG binds to type II NADH dehydrogenase (NDH-2), an essential enzyme catalyzing the transfer of electrons from NADH to quinones in the electron transport chain (ETC), blocking electron transfer in S. aureus. Last, we validated the efficacy of DPPG in vivo through animal infection models. Our findings not only provide a distinct antibiotic lead to treat multidrug resistant pathogens but also identify a promising antibacterial target., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

The current study offers a metal-free, direct, and successful synthesis technique for a new series of quinolinone and benzo[d][1,3]oxazine, along with an assessment of their biological activities. Heteroannulation of anthranilic acid with carbonyl-containing chemicals (aroyl pyruvate, ethyl acetoacetatete, maleic anhydride, and ethyl cyanoacetate) resulted in the desired quinolones and benzo[d][1,3]oxazines. This technique introduces a number of fundamental breakthroughs in organic synthesis, including metal-free catalysts, smart reaction conditions with column purification, and a wide functional scope. Furthermore, the structure of the newly synthesized chemical series was investigated and validated using spectroscopic techniques. The synthesized series were evaluated for antibacterial (against gram-positive and gram-negative bacterial strains) and antifungal activity. The quinolone and benzo[d][1,3]oxazine candidates had remarkable antibacterial action. Furthermore, molecular docking investigations corroborated the biological studies using the Molecular Operating Environment and Petro Osiris Molinspiration (POM) experiments, which confirmed the activity of compounds 8, 15, and 17. Our studies on the cytotoxic activity of various chemicals have demonstrated that these compounds exhibit minimal toxicity. Specifically, when comparing the cytotoxic effects on human lung fibroblast (WI38) cells to those of Doxorubicin, a well-known chemotherapy agent, compounds 8, 15, and 17 showed weak cytotoxic effects on the normal WI38 cells. This indicates that these compounds may possess some level of selectivity and reduced toxicity towards normal cells, suggesting potential for further exploration as antibacterial agents with a safer profile for normal cells., Competing Interests: Declarations. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

The rising resistance of various pathogens and the demand for materials that prevent infections drive the need to develop broad-spectrum antimicrobial membranes capable of combating a range of microorganisms, thereby enhancing safety in biomedical and industrial applications. Herein, we introduce a simple and efficient technique to engineer membranes composed of polylactic acid (PLA) and polybutylene adipate terephthalate (PBAT) biopolymers and α-Ag 2 WO 4 particles using an electrospinning technique. The corresponding structural, thermal, mechanical, and antimicrobial properties were characterized. X-ray diffraction (XRD) patterns confirmed the integration of crystalline α-Ag 2 WO 4 within the polymer matrix. Scanning electron microscopy (SEM) and Raman confocal microscopy revealed uniformly dispersed α-Ag 2 WO 4 particles in the electrospun fibers, influencing their diameter and surface roughness. Thermal analysis indicated adjustments in the thermal stability and crystallinity of the composites with an increasing α-Ag 2 WO 4 content. Dynamic mechanical analysis (DMA) highlighted variations in storage modulus and glass transition temperatures due to interactions between α-Ag 2 WO 4 and polymer chains, with tensile tests showing an increase in elastic modulus and ultimate tensile strength as the α-Ag 2 WO 4 content increased. Antimicrobial assessments revealed that PLA/PBAT membranes with α-Ag 2 WO 4 showed pronounced antibacterial activity, forming inhibition halos across all samples against Pseudomonas aeruginosa , methicillin-resistant Staphylococcus aureus , and Mycobacterium smegmatis (a surrogate for Mycobacterium tuberculosis ). These membranes also exhibited potent antiviral activity against bacteriophage phi 6, a surrogate for SARS-CoV-2, suggesting potential applications in combating infections caused by enveloped viruses. The antimicrobial activities are attributed to the generation of reactive oxygen species (ROS) and the controlled release of Ag + ions. This work underscores the multifaceted capabilities of α-Ag 2 WO 4 -enhanced PLA/PBAT membranes in combating bacterial and viral growth, where both durability and microbial resistance are critical. Taken together, our findings provide a solution for obtaining advanced materials to be applied in a wide range of industrial applications, such as filtration systems, food preservation, antimicrobial coatings, protective textiles, and cleaning products.

Our aim in this study was to explain the biological activity of the latest azafluoranthene. The natural product sarumine ( 12 ) and its derivatives ( 13 - 17 ) were synthesized and evaluated for their antibacterial and antitumor activities. The synthesis involved a simplified reaction pathway based on biaryl-sulfonamide-protected cyclization, and the compounds were characterized and studied using spectroscopic methods ( 1 HNMR and 13 CNMR). Most of the compounds demonstrated improved antibacterial activity. Notably, sarumine demonstrated potent activity against S. aureus and B . subtilis , with an MIC of 8 μg/mL, showing comparable inhibitory effects to the positive control. Furthermore, molecular simulation studies indicated that sarumine exhibited significant binding affinity to FabH. The inhibitory effect of Cl was superior to the others on the structure, and the antitumor activity result also suggested that the inhibitory ability in PC-3 displayed by the R 1 derivatives of F and Cl substitutions was better than that of MDA-MB-231. These findings suggest that sarumine and its derivatives may represent new and promising candidates for further study.

It remains a challenge to endow a polymeric material with antithrombotic ability by surface grafting without disturbing the bulk properties of the substrate. Heparin-based functional structures of less than 80 nm were fabricated and covalently grafted on a polyethylene terephthalate surface via carbene chemistry (Hep-g-PET). Heparin was oxidized with the minimum antithrombrin sequence retained, creating an aldehyde group on the chain terminus. Oxidized heparin was then covalently attached to a poly(amidoamine) (PAMAM)-grafted PET substrate. The interface between blood and PET was improved by the surface functionality, and the amount of attached platelets decreased to 29 ± 12.1% of its initial value. The bulk properties of the functionalized film were hardly influenced, and the visible light transmittance remained more than 96%. The tethered structures also showed the ability to kill attached S. aureus and E. coli efficiently. The functionalized membrane showed negligible ex vivo cell cytotoxicity and a low hemolysis ratio. Hep-g-PET was implanted in between rat skin and muscle, and showed an outstanding histological response and antimicrobial ability. The influences of the graft thickness and the heparin chain length were explored. The strategies reported in this work may help to improve the design of polymeric implant bio-devices.

The overuse of antibiotics has accelerated antibiotic resistance, and it is a significant global threat to public health. To combat the rising threat of drug-resistant microbes, antimicrobial photodynamic therapy (APDT) has emerged as a promising alternative therapeutic strategy. This study focuses on the synthesis of eco-friendly lignin-derived gold-titanium dioxide nanophotocomposites (L@Au-TiO 2 NCs). Lignin was utilized as a sustainable precursor for the synthesis of L@Au-TiO 2 NCs. The gold and TiO 2 nanoparticles possess inherent photodynamic properties, and thus the developed L@Au-TiO 2 NCs exhibit enhanced antimicrobial efficacy due to the synergistic combination of their attributes. The antimicrobial potential of the L@Au-TiO 2 NCs was evaluated against various microbial strains ( Escherichia coli , Bacillus megaterium , and Candida tropicalis ) under dark and green light conditions. The outcome of this study highlights the promising potential of L@Au-TiO 2 NCs for photodynamic antimicrobial applications. The L@Au-TiO 2 nanophotocomposites could be explored in the fields of medicine and nanotechnology to introduce innovative ideas into the biomedical field.

The increasing number of infections caused by pathogenic bacteria has severely affected human society. More and more deaths were originated from Gram-positive methicillin-resistant Staphylococcus aureus (MRSA) infection each year. The potential and excellent bacteriostatic activity and resistance to biofilm formation of pillar[5]arene with different functional groups attract important attention to further study the relationship between antimicrobial activity and cytotoxicity by varying the length of the hydrophobic chain, the number of positive charges, and the hydrophobic/hydrophilic balance of the molecule. In this work, four pyridinium-based cationic pillar[5]arene ( PP s) with linear aliphatic chains of different lengths were synthesized. After systematic characterization, their inhibition activities against S. aureus were investigated. It revealed that PP6 (six methylenes in each linker) exhibited excellent inhibition activity against S. aureus (ATCC 6538) with a minimum inhibitory concentration (MIC) of 3.91 μg/mL and a minimum bactericidal concentration (MBC) of 62.50 μg/mL. As expected, PP6 exhibited the strongest antibiofilm ability and negligible antimicrobial resistance even after the 20th passage. A study of the action mechanism of selected PP s on the bacterial membrane depolarization and permeability by transmission electron microscopy (TEM) disclosed that the cationic pyridine groups of PP s inserted into the negatively charged bacterial membranes, thereby leading to membranolysis, cytoplasmic content leakage, and cell death. Importantly, PP s all showed very low toxicity to mammalian cells (L929 and HBZY-1), which provided a significant reference for the construction of hypotoxic antibacterial biomaterials for multiple drug-resistant bacteria based on pyridinium-grafted cationic macrocycles with controllable hydrophobic chain lengths.

Biofilm formation on medical implants such as catheters is a major issue which needs to be addressed as it leads to severe health care associated infections. This study explored the design and synthesis of a polydopamine-lipopeptide based antimicrobial coating. The coating was used to modify the surface of Ultrathane Catheters. The lipopeptide SL1.15 with an N -terminal cysteine was covalently conjugated to the polydopamine modified catheters via a Michael addition reaction between the thiol moiety in the peptide and the aromatic ring in the polydopamine layer. The immobilization of the peptide on the polydopamine coated catheters was confirmed using water contact angle, X-ray photoelectron spectroscopy, atomic force microscopy, and scanning electron microscopy (SEM). The antimicrobial activity of the coated catheters investigated using drug resistant and clinical strains of Gram-positive (MRSA and S. aureus ) and Gram-negative ( E. coli , A. baumannii , and P. aeruginosa ) bacteria revealed that lipopeptide immobilization inhibited >90% bacterial adhesion to the catheter surface. Additionally, biofilm assays against MRSA and E. coli revealed that the lipopeptide immobilized catheters inhibited >85% bacterial growth after 1 week incubation. Finally, the cytotoxicity profile of the catheters using the human dermal fibroblast, and the human embryonic kidney cell lines demonstrated that the polydopamine-lipopeptide coating was not toxic after 72 h incubation.

Multidrug-resistant (MDR) Gram-negative bacteria infections have gradually become a more serious health problem recently, and antibacterial drugs are urgently needed to tackle MDR Gram-negative bacteria. Herein, we synthesized a series of quaternary ammonium salt derivatives of hyperbranched polylysine (HPL- Cm - n ) with different alkyl chain lengths ( m = 4, 8, 12, 16) and grafting ratios ( n = 5.8-21.0) of alkyl quaternary ammonium salts ( Cm ). HPL- Cm - n s exhibited excellent antibacterial activities against drug-sensitive E. coli and P. aeruginosa , and specifically, HPL-C12- n s were also highly active against MDR E. coli and P. aeruginosa . The cytotoxicity and hemolytic activity of HPL- Cm - n s increased with the increase in the alkyl chain length and the grafting ratio of Cm . The killing study proved that HPL-C12-9.5 had fast killing kinetics and was bactericidal toward both drug-sensitive and MDR E. coli . The mechanistic studies showed that, similar to hyperbranched polylysine (HPL), HPL-C12-9.5 killed bacteria by disrupting the cell membranes and causing leakage of the cytoplasmic contents. HPL-C12- n s might have potential as an antibacterial agent to combat MDR Gram-negative bacteria.