Search

Since the discovery of antimicrobial agents, the misuse of antibiotics has led to the emergence of bacterial strains resistant to both antibiotics and common disinfectants like quaternary ammonium compounds (QACs). A new class, 'gemini' QACs, which contain two polar heads, has shown promise. Octenidine (OCT), a representative of this group, is effective against resistant microorganisms but has limitations such as low solubility and high cytotoxicity. In this study, we developed 16 novel OCT derivatives. These compounds were subjected to in silico screening to predict their membrane permeation. Testing against nosocomial bacterial strains (G + and G - ) and their biofilms revealed that most compounds were highly effective against G + bacteria, while compounds 7, 8, and 10-12 were effective against G - bacteria. Notably, compounds 6-8 were significantly more effective than OCT and BAC standards across the bacterial panel. Compound 12 stood out due to its low cytotoxicity and broad-spectrum antimicrobial activity, comparable to OCT. It also demonstrated impressive antifungal activity. Compound 1 was highly selective to fungi and four times more effective than OCT without its cytotoxicity. Several compounds, including 4, 6, 8, 9, 10, and 12, showed strong virucidal activity against murine cytomegalovirus and herpes simplex virus 1. In conclusion, these gemini QACs, especially compound 12, offer a promising alternative to current disinfectants, addressing emerging resistances with their enhanced antimicrobial, antifungal, and virucidal properties., 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 authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Jan Marek reports financial support was provided by Ministry of Health of the Czech Republic. 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.)

Three series of thiazolidinedione (TZD) derivatives (5a-f, 7a-f, and 9a-f) were prepared efficiently. Afterward, the synthesized candidates' antibacterial efficacy against both gram-positive and gram-negative bacteria was assessed. Compounds 7c, 7d, and 7f had values comparable to that of ampicillin, a reference antibiotic, whereas compounds 5c, 5d, and 7e exhibited the greatest values (23.0±1.0, 27.7±0.6, and 20.0±1.0, respectively) against gram-positive bacteria (Staphylococcus aureus). The optimal structure of the produced molecules was determined by DFT computing. To assess the binding energy and elucidate the interaction between the potential candidates and different proteins, in silico docking is employed. ADMET analysis to assess the synthesized compounds' toxicity, metabolism, excretion, distribution, and absorption., (© 2024 Wiley-VHCA AG, Zurich, Switzerland.)

Thirty protoberberine derivatives, of which twenty five were new, were synthesized and evaluated for their anti-Helicobacter pylori (HP) activities, taking 2,3,10-trimethoxy-9-p-methylbenzylaminoprotopalmatine chloride 1 as the lead. Among them, berberine (BBR) derivative 7c displayed the highest potency against six tested metronidazole (MTZ)-resistant strains and two tested MTZ-susceptible strains with the MIC values of 0.4-1.6 μg/mL with favorable druglike profiles including low toxicity and high stabilities in plasma and artificial gastric fluid. Mechanistic study revealed that 7c might target HP urease with IC 50 value of 0.27 μg/mL against Jack bean urease. Furthermore, 7c might change the permeability of the bacterial membrane and direct interact with HP DNA, which also contribute to its bactericidal activity. Therefore, BBR derivatives constituted a new family of anti-HP candidates, with the advantage of good safety profile and multi-target mechanisms, and are worthy 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 Inc. All rights reserved.)

With the emergence of drug-resistance, there is a need for novel anti-bacterials or to enhance the efficacy of existing drugs. In this study, Patuletin (PA), a flavanoid was loaded onto Gallic acid modified Zinc oxide nanoparticles (PA-GA-ZnO), and evaluated for antibacterial properties against Gram-positive (Bacillus cereus and Streptococcus pneumoniae) and Gram-negative (Samonella enterica and Escherichia coli) bacteria. Characterization of PA, GA-ZnO and PA-GA-ZnO' nanoparticles was accomplished utilizing fourier-transform infrared spectroscopy, efficiency of drug entrapment, polydispersity index, zeta potential, size, and surface morphology analysis through atomic force microscopy. Using bactericidal assays, the results revealed that ZnO conjugation displayed remarkable effects and enhanced Patuletin's effects against both Gram-positive and Gram-negative bacteria, with the minimum inhibitory concentration observed at micromolar concentrations. Cytopathogenicity assays exhibited that the drug-nanoconjugates reduced bacterial-mediated human cell death with minimal side effects to human cells. When tested alone, drug-nanoconjugates tested in this study showed limited toxic effects against human cells in vitro. These are promising findings, but future work is needed to understand the molecular mechanisms of effects of drug-nanoconjugates against bacterial pathogens, in addition to in vivo testing to determine their translational value. This study suggests that Patuletin-loaded nano-formulation (PA-GA-ZnO) may be implicated in a multi-target mechanism that affects both Gram-positive and Gram-negative pathogen cell structures, however this needs to be ascertained in future work., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Antibiotic abuse is increasing the present rate of drug-resistant bacterial wound infections, producing a significant healthcare burden globally. Herein, we prepared a pH-responsive CMCS/PVP/TA (CPT) multifunctional hydrogel dressing by embedding the natural plant extract TA as a nonantibiotic and cross-linking agent in carboxymethyl chitosan (CMCS) and polyvinylpyrrolidone (PVP) to prompt wound healing. The CPT hydrogel demonstrated excellent self-healing, self-adaptive, and adhesion properties to match different wound requirements. Importantly, this hydrogel showed pH sensitivity and exhibited good activity against resistant bacteria and antioxidant activity by releasing TA in case of bacterial infection (alkaline). Furthermore, the CPT hydrogel exhibited coagulant ability and could rapidly stop bleeding within 30 s. The biocompatible hydrogel effectively accelerated wound healing in a full-thickness skin defect model by thickening granulation tissue, increasing collagen deposition, vascular proliferation, and M2-type macrophage polarization. In conclusion, this study demonstrates that multifunctional CPT hydrogel offers a candidate material with potential applications for infected skin wound healing., 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.)

To evaluate the biotransformation and the mechanism of binding as well as the biological impact of metal-based- drugs involving Pd(II), known to have high potency and low toxicity for use as anticancer therapeutics, in the present study, a newly synthesized palladium (II) complex, [Pd(CPF)(OH 2 ) 2 ] 2+ (where CPF is ciprofloxacin), has been synthesized and characterized and thoroughly evaluated for its antimicrobial properties. The interaction of the diaqua complex with CT-DNA and BSA was studied through various techniques, including UV-vis spectroscopy, thermal denaturation, viscometry, gel electrophoresis, ethanol precipitation, and molecular docking studies. The results indicate that the complex exhibits a robust binding interaction with CT-DNA, possibly via minor groove binding and (or) electrostatic interactions. Furthermore, the complex displays good binding affinity towards BSA, indicating its potential as a target for DNA and BSA in biological media. The invitro cytotoxicity assay reveals that this complex can be classified as a promising cell growth inhibitor against MCF-7, HT-29, and A549. Thus, this newly synthesized palladium (II) complex is a promising candidate for further exploration as a potential anticancer therapeutic., (© 2024 Wiley-VHCA AG, Zurich, Switzerland.)

The present study reports the green synthesis of pectin-fabricated silver nanocomposites (Pectin-AgNPs) using Carpesium nepalense leaves extract, evaluating their bactericidal kinetics, in vivo hepatoprotective, and cytotoxic potentials along with possible mechanisms. GC/MS and LC/MS analyses revealed novel phytochemicals in the plant extract. The Pectin-AgNPs were characterized using UV/Vis, AFM, SEM, TEM, DLS, FTIR, and EDX techniques, showing a spherical morphology with a uniform size range of 50-110 nm. Significant antibacterial activity (P < 0.005) was found against four bacterial strains with ZIs of 4.1 ± 0.15 to 27.2 ± 3.84 mm. AFM studies revealed significant bacterial cell membrane damage post-treatment. At 0.05 mg/kg, the nanocomposites showed significant (P < 0.005) hepatoprotective activity in biochemical and histopathology analyses compared to the CCl 4 control group. Pectin-AgNPs significantly reduced (P < 0.005) LDH, AST, ALT, ALP, and DB levels. qPCR analysis showed ameliorative effects on PPARs and Nrf2 gene expression, restoring gene alterations caused by CCl 4 intoxication. In vivo acute toxicity studies confirmed low toxicity of Pectin-AgNPs in major organs. Pectin-AgNPs exhibited cytotoxic activity against HeLa cell lines at higher doses with an LC 50 of 223.7 μg/mL. These findings demonstrate the potential of Pectin-AgNPs as promising antibacterial, hepatoprotective, and cytotoxic agents., 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.)

Stachys maritima is a species of plant belonging to the Lamiaceae, commonly known as common sea lavender. The extraction of S. maritima involves drying the aerial parts, grinding them into powder, followed by extraction with methanol. ST-CQDs (S. maritima carbon quantum dots) were synthesized from S. maritima extract via pyrolysis. An optimal synthesis condition of 7 hours of pyrolysis was determined to yield ST-CQDs with high absorption in the visible-UV range. Characterization techniques such as UV-visible spectroscopy and TEM (Transmission Electron Microscopy) confirmed the spherical and homogeneous nature of the carbon quantum dots. S. maritima methanol extract exhibited strong antioxidant activity with a DPPH (2,2-Diphenyl-1-picrylhydrazyl) IC 50 value of 0.114±0.001 mg/mL. Similarly, ST-CQDs showed strong antioxidant properties with a DPPH IC 50 value of 0.69±0.03 mg/mL. Moreover, the methanol extract of S. maritima demonstrated antimicrobial activity against E. coli ATCC 25922 and S. aureus ATCC 25923, with effective MIC values of 25 mg/mL and 6.25 mg/mL, respectively. However, ST-CQDs did not show antimicrobial effects against the tested microorganisms (E. coli ATCC 25922, S. aureus ATCC 25923, K. pneumoniae ATCC 13883, and C. albicans ATCC 10231). Molecular docking simulations suggested that compounds derived from S. maritima (such as 9,12,15-octadecatrienoic acid and palmitic acid) could interact effectively with TNF-α (Tumor Necrosis Factor Alpha), indicating potential anti-inflammatory properties. This study highlights that the methanol extract of S. maritima possesses potent antioxidant and antimicrobial activities, and ST-CQDs exhibit similar antioxidant properties. However, ST-CQDs did not demonstrate antimicrobial activity against the tested pathogens. Molecular docking simulations also suggest potential anti-inflammatory properties of compounds derived from the plant., (© 2024 Wiley-VHCA AG, Zurich, Switzerland.)

In the present work, a new class of thiazole-isatin-1,2,3-triazole hybrids (5 a-5 p) and precursor alkyne hybrids (6 a-6 d) has been reported with their in-silico studies. After structural identifications using different spectroscopic technique such as FTIR, 1 H and 13 C NMR and HRMS, the synthesized hybrids were explored for their biological potential using molecular docking and molecular dynamics calculations. Molecular docking results revealed that compound 5 j showed maximum binding energy i. e. -10.3 and -12.6 kcal/mol against antibacterial and antifungal enzymes; 1KZN (E. coli) and 5TZ1 (C. albicans), respectively. Molecular dynamics simulations for the best molecule (100 ns) followed by PBSA calculations suggested a stable complex of 5 j with 5TZ1 with binding energy of -118.760 kJ/mol as compared to 1KZN (-94.593 kJ/mol). The mean RMSD values for the 1KZN with 5 j complex remained approximately 0.175 nm throughout all the time span of 100 ns in the production stages and is in the acceptable range. Whereas, 5TZ1 with 5 j complex, RMSD values exhibited variability within the range of 0.15-0.25 nm., (© 2024 Wiley-VHCA AG, Zurich, Switzerland.)

To improve the solubility of the fluoroquinolone drug fleroxacin (FL), based on the previous experience of our research group in synthesizing co-crystals/salts of quinolone drugs to improve the physicochemical properties of drugs, Fleroxacin-D-tartaric acid dihydrate salt (FL-D-TT, C 17 H 19 F 3 N 3 O 3 ·C 4 H 5 O 6 ·2(H 2 O)), was synthesized for the first time using fleroxacin and D/L-tartaric acid (D/L-TT). Structural characterization of FL-D-TT was carried out using single-crystal X-ray diffraction, infrared spectral analysis (FT-IR) and powder X-ray diffraction (PXRD). Molecular electrostatic potential analysis showed that D-tartaric acid interacted more readily with FL than L-tartaric acid. The solubility of FL-D-TT (9.71 mg/mL, 1.82 mg/mL) was significantly higher compared to FL (0.39 mg/mL, 0.71 mg/mL) in water and buffer solution at pH 7.4. This may be attributed to the formation of charge-assisted hydrogen bonds (CAHBs) between FL and D-TT that facilitates the dissociation of FL cations in the dissolution medium, leading to an increase in FL solubility. This also led to some improvement in the in vitro antimicrobial activity of FL-D-TT against E. coli, S. typhi, and S. aureus. In addition, the hygroscopic stability of FL has been improved. Surprisingly, FL-D-TT had better photostability than FL, which could be attributed to the introduction of D-TT to make the photosensitizing moiety of FL more stable, which led to the improvement of the photostability of FL., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Plant pathogens cause substantial crop losses annually, posing a grave threat to global food security. Fungicides have usually been used for their control, but the rapid development of pesticide resistance renders many ineffective, therefore the search for novel and efficient green pesticides to prevent and control plant diseases has become the top priority in crop planting., Results: The results of bioassay studies indicated that most of the target compounds showed certain antimicrobial activity in vitro. In particular, compound X7 showed high inhibitory activity against Xanthomonas oryzae pv. oryzae (Xoo), with an EC 50 value of 27.47 μg mL -1 , surpassing conventional control agents such as thiazole zinc (41.55 μg mL -1 ) and thiodiazole copper (53.39 μg mL -1 ). Further studies on molecular docking showed that X7 had a strong binding affinity with 2FBW. The morphological change observed by scanning electron microscopy indicated that the surface of Xoo appears wrinkled and cracked under X7 treatment and a total of 2662 proteins were identified by label-free proteomic analysis. Three experiments have elucidated the mechanism whereby X7 induced considerable changes in the physiological and biochemical properties of Xoo, which in turn affected the reproduction and growth of bacteria., Conclusion: This work represents a pivotal advancement, offering important reference for the research and development therapeutics in combating plant pathogens. © 2024 Society of Chemical Industry., (© 2024 Society of Chemical Industry.)

Antimicrobial resistance is a global healthcare challenge that urgently needs the development of new therapeutic agents. Antimicrobial peptides and mimics thereof are promising candidates but mostly suffer from inherent toxicity issues due to the non-selective binding of cationic groups with mammalian cells. To overcome this toxicity issue, this work herein reports the synthesis of a smart antimicrobial dendron with masked cationic groups (Gal-Dendron) that could be uncaged in the presence of β-galactosidase enzyme to form the activated Enz-Dendron and confer antimicrobial activity. Enz-Dendron show bacteriostatic activity toward Gram-negative (P. aeruginosa and E. coli) and Gram-positive (S. aureus) bacteria with minimum inhibitory concentration values of 96 µm and exerted its antimicrobial mechanism via a membrane disruption pathway, as indicated by inner and outer membrane permeabilization assays. Crucially, toxicity studies confirmed that the masked prodrug Gal-Dendron exhibited low hemolysis and is at least 2.4 times less toxic than the uncaged cationic Enz-Dendron, thus demonstrating the advantage of masking the cationic groups with responsive immolative linkers to overcome toxicity and selectivity issues. Overall, this study highlights the potential of designing new membrane-disruptive antimicrobial agents that are more biocompatible via the amine uncaging strategy., (© 2024 The Author(s). Macromolecular Rapid Communications published by Wiley‐VCH GmbH.)

Antibiotic resistance and the rise of untreatable bacterial infections pose severe threats to human health. Silver nanoparticles (AgNPs) have emerged as a promising antibacterial solution due to their broad-spectrum effectiveness. However, their relatively high cytotoxicity has limited their widespread application. In this study, ferulic acid (FA) was used as a reducing agent, while silver oxide served as a silver precursor to rapidly prepare FA-derived lignin (FAL) coated AgNPs (AgNPs@FAL) with a size ranging from 34.8 to 77.1 nm. Density functional theory (DFT) calculations indicated that the coating of FAL endowed AgNPs@FAL with high stability, preventing the oxidation of AgNPs prior to antibacterial applications. Cell experiments further indicated that AgNPs@FAL exhibited lower cell toxicity (∼80 % viability of normal kidney cells cultured at 25 μg/mL AgNPs@FAL) compared to fully exposed commercially available citrate-modified AgNPs (AgNPs@CA). Antibacterial experiments revealed that the minimum inhibitory concentrations (MIC) of AgNPs@FAL against E. coli and S. aureus were 12.5 μg/mL and 25 μg/mL, respectively, surpassing the antibacterial effect of AgNPs@CA, as well as ampicillin and penicillin. Additionally, AgNPs@FAL was capable of disrupting E. coli and S. aureus biofilm formation. This novel AgNPs@FAL formulation presents a promising antibacterial solution, addressing limitations observed in conventional drugs., Competing Interests: Declaration of competing interest We declare that we 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.)

The decline of antibiotics efficacy worldwide has recently reached a critical point urging for the development of new strategies to regain upper hand on multidrug resistant bacterial strains. In this context, the raise of photodynamic therapy (PDT), initially based on organic photosensitizers (PS) and more recently on organometallic PS, offers promising perspectives. Many PS exert their biological effects through the generation of reactive oxygen species (ROS) able to freely diffuse into and to kill surrounding bacteria. Hijacking of the bacterial iron-uptake systems with siderophore-PS conjugates would specifically target pathogens. Here, we report the synthesis of unprecedented conjugates between the siderophore desferrioxamine B (DFOB) and an antibacterial iridium(III) PS. Redox properties of the new conjugates have been determined at excited states and compared to that of an antibacterial iridium PS previously reported by our groups. Tested on nosocomial pathogen Pseudomonas aeruginosa and other bacteria, these conjugates demonstrated significant inhibitory activity when activated with blue LED light. Ir(III) conjugate and iridium free DFOB-2,2'-dipyridylamine ligands were crystallized in complex with FoxA, the outer membrane transporter involved in DFOB uptake in P. aeruginosa and revealed details of the binding mode of these unprecedented conjugates., 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 Authors. Published by Elsevier Ltd.. All rights reserved.)

Acinetobacter baumannii with the capability to "escape" almost all currently available antibacterials is eroding the safety of basic medical interventions and is an increasing cause of mortality globally, prompting a substantial requirement for new classes of antibacterial agents. Indoles participate in the regulation of persistent bacterial formation, biofilm formation, plasmid stability, and drug resistance. In particular, indole hybrids demonstrated promising antibacterial activity against both drug-sensitive and drug-resistant A. baumannii pathogens, representing a fertile source for the discovery of novel therapeutic agents for clinical deployment in controlling A. baumannii infections. This mini-review outlines the current innovations of indole hybrids with antibacterial activity against A. baumannii pathogens, covering articles published from 2020 to the present, to open new avenues for exploring novel anti-A. baumannii candidates., (© 2024 Deutsche Pharmazeutische Gesellschaft.)

Schiff bases of existing antimicrobial drugs are an area, which is still to be comprehensively explored to improve drug efficiency against consistently resisting bacterial species. In this study, we have targeted a new and eco-friendly method of condensation reaction that allows the "green synthesis" as well as improved biological efficacy. The transition metal complexes of cefpodoxime with well-enhanced biological activities were synthesized. The condensation reaction product of cefpodoxime and vanillin was further reacted with suitable metal salts of [Mn (II), Cu (II), Fe (II), Zn (II), and Ni (II)] with 1:2 molar ratio (metal: ligand). The characterization of all the products were carried out by using UV-Visible, elemental analyzer, FTIR, 1 H-NMR, ICP-OES, and LC-MS. Electronic data obtained by UV-Visible proved the octahedral geometry of metal complexes. The biological activities Schiff base ligand and its transition metal complexes were tested by using in-vitro anti-bacterial analysis against various Gram-negative, as well as Gram-positive bacterial strains. Proteinase and protein denaturation inhibition assays were utilized to evaluate the products in-vitro anti-inflammatory activities. The in vitro antioxidant activity of the ligand and its complexes was evaluated by utilizing the 2,2-diphenyl-1-picrylhydrazyl (DPPH) in-vitro method. The final results proved metal complexes to be more effective against bacterial microorganisms as compared to respective parent drug as well as their free ligands. Patch Dock, a molecular docking tool, was used to dock complexes 1a-5e with the crystal structure of GlcN-6-P synthase (ID: 1MOQ). According to the docking results, complex 2b exhibited a highest score (8,882; ACE = -580.43 kcal/mol) that is well correlated with a high inhibition as compared to other complexes which corresponds to the antibacterial screening outcomes., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Ketolides (3-keto) such as TE-802 and acylides (3-O-acyl) like TEA0929 are ineffective against constitutively resistant pathogens harboring erythromycin ribosomal methylation (erm) genes. Following our previous work on alkylides (3-O-alkyl), we explored the structure-activity relationships of hybrids combining (R/S) 3-descladinosyl erythromycin with 6/7-quinolone motifs, featuring extended ether-linked spacers, with a focus on their efficacy against pathogens bearing constitutive erm gene resistance. Optimized compounds 17a and 31f not only reinstated efficacy against inducibly resistant pathogens but also demonstrated significantly augmented activities against constitutively resistant strains of Streptococcus pneumoniae and Streptococcus pyogenes, which are typically refractory to existing C-3 modified macrolides. Notably, hybrid 31f (coded ZN-51) represented a pioneering class of agents distinguished by its dual modes of action, with ribosomes as the primary target and topoisomerases as the secondary target. As a novel chemotype of macrolide-quinolone hybrids, alkylide 31f is a valuable addition to our armamentarium against macrolide-resistant bacteria., 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 the following financial interests/personal relationships which may be considered as potential competing interests: Jian-Hua Liang reports financial support was provided by Sichuan Science and Technology Program. Jian-Hua Liang reports financial support was provided by the National Natural Science Foundation of China. Jian-Hua Liang has patent #CN2024109090844 pending to China national intellectual property Administration. 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.)

Chitosan exhibits good biocompatibility and some antibacterial activity, making it a popular choice in biomedicine, personal care products, and food packaging. Despite its advantages, the limited antibacterial effectiveness of chitosan hinders its widespread use. Introducing a six-membered heterocyclic structure through chemical modification can significantly enhance its antimicrobial properties and broaden its potential applications. In order to explore the effect of six-membered heterocyclic structure on the antibacterial and antibiofilm activities of chitosan. In this study, seven chitosan derivatives containing six-membered heterocyclics were prepared. They were characterized using Fourier transform infrared (FT-IR) spectroscopy, nuclear magnetic resonance (NMR) spectroscopy, and elemental analysis. Cell viability assay showed that they were non-toxic. The antibacterial and antibiofilm activities against Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus) were evaluated. Our research findings demonstrate that increasing the hydrophobicity, alkalinity and charge density of the substitute groups improved the antibacterial and antibiofilm activities of chitosan. This study also offers valuable insights into the quantitative structure-activity relationships of chitosan derivatives in terms of antibacterial and antibiofilm activities., 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.)

Angucyclines and angucyclinones represent a class of natural compounds that belong to the group of aromatic polyketides. They exhibit a wide array of biological properties, such as antimicrobial, antiviral, and cytotoxic. Their considerable therapeutic potential and diverse scaffolds have attracted many synthetic chemists to devise novel strategies to construct their intricate molecular architecture. Over 300 class members have been isolated from natural sources, mainly from bacterial strains of Streptomyces species. This review highlights recent advancements in their synthesis, such as oxidative cyclization, photooxidation, and metal-catalyzed [4+2]-cycloaddition, which has facilitated the efficient and practical total syntheses of various angucycline and angucyclinone natural products., (© 2024 The Authors. ChemPlusChem published by Wiley-VCH GmbH.)

Quaternary ammonium compounds have served as a first line of protection for human health as surface disinfectants and sanitizers for nearly a century. However, increasing levels of bacterial resistance have spurred the development of novel QAC architectures. In light of the observed reduction in eukaryotic cell toxicity when the alkyl chains on QACs are shorter in nature (≤10 C), we prepared 47 QAC architectures that bear multiple short alkyl chains appended to up to three cationic groups, thus rendering them "bushy-tailed" multiQACs. Antibacterial activity was strong (often ~1-4 μM) in a varied set of bushy-tailed architectures, though observed therapeutic indices were not significantly improved over QAC structures bearing fewer and longer alkyl chains., (© 2024 Wiley-VCH GmbH.)

The novel donor-acceptor (D-A) type covalent organic frameworks TATF-COF and TATP-COF, with multiple fluorine groups as electron storage units, were successfully constructed to achieve efficient charge transfer and photocatalytic activity for antibacterial photocatalytic therapy. Fluorine, the most electronegative element, was utilized as an electron-withdrawing substituent for the acceptor, which could unite the donor unit together and efficiently improve the charge transfer from the donor to acceptor. The unique D-A structures of TATF-COF and TATP-COF ensure that they have narrow band gaps, strong photocurrent responses, long fluorescence lifetimes, and good capacity to generate reactive oxygen species (ROS) to realize good antibacterial activity. Meanwhile, the inclusion of multiple hydrophilic fluorine groups means that TATF-COF and TATP-COF are highly water dispersible, which is also beneficial in terms of promoting the generation of adequate quantities of ROS. Hence, in view of their excellent photoelectric properties and good water dispersibility, further investigations were performed, and excellent antibacterial activities in vitro against both gram-negative and gram-positive bacteria were demonstrated for TATF-COF and TATP-COF. In addition, we also showed that they can function as effective antibacterial dental materials., 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.)

Background: To discover more efficient agricultural antimicrobial agents, a series of new quinazoline derivatives containing both a piperazine linker and the N-acetyl moiety were prepared and assessed for their antibacterial and antifungal activities., Results: All the target compounds were characterized by 1 H and 13 C NMR as well as high-resolution mass spectrometry (HRMS), and the chemical structure of the most potent compound E19 incorporating a 4-trifluoromethoxy substituent was clearly confirmed via single crystal X-ray diffraction measurements. The bioassay results indicated that some compounds possessed notable inhibitory effects in vitro against the bacterium Xanthomonas oryzae pv. oryzicola (Xoc). For example, compound E19 had an EC 50 (effective concentration for 50% activity) value of 7.1 μg/mL towards this pathogen, approximately 15- and 10-fold more effective than the commercial bactericides thiodiazole copper and bismerthiazol (EC 50  = 110.2 and 72.4 μg/mL, respectively). Subsequently, the mechanistic studies showed that compound E19 likely exerted its antibacterial efficacies by altering the cell morphology, increasing the permeability of bacterial cytoplasmic membrane, suppressing the production of bacterial extracellular polysaccharides and the extracellular enzyme activities (amylase and cellulase), and blocking the swimming motility of Xoc. Moreover, the proteomic analysis revealed that compound E19 could reduce the bacterial flagellar biosynthesis and decrease the flagellar motility by down-regulating the expression of the related differential proteins., Conclusion: Compound E19 exhibited good potential for further development as a bactericide candidate for control of Xoc. © 2024 Society of Chemical Industry., (© 2024 Society of Chemical Industry.)

Studies have confirmed that the spatial arrangement of chiral molecules has a decisive influence on supramolecular assembly. However, the effect of epimerization caused by the change of a single chiral center on the self-assembly of chiral molecules has not been reported. Herein, we explored a pair of epimers 18 α-glycyrrhetinic acid and 18 β-glycyrrhetinic acid from Glycyrrhiza uralensis Fisch, which had completely different medicinal activities. In this study, we found that these epimers of glycyrrhetinic acid showed distinct self-assembly properties under the condition of the deionized water and a small amount of DMSO solution. Interestingly, the cis-configured 18 β-GA could form a 'head-to-tail' interlaced structure and further self-assembled to form nanoparticles, while trans-configured 18 α-GA was connected in a "head-to-head" manner, and due to the excessive steric hindrance that made it difficult to assemble. This work not only clearly demonstrates the impact of epimerization due to changes in a single chiral center on the self-assembly of chiral molecules as well as biological activity, but also provides new insights into the self-assembly of natural organic molecules in the development of nanomedicines and biofunctional materials., 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.)

High-throughput synthesis and screening of chemical libraries play pivotal roles in drug discovery. Click chemistry has emerged as a powerful strategy for constructing highly modular chemical libraries. However, the development of new click reactions and unlocking new clickable building blocks remain exceedingly challenging. Herein, we describe a double-click strategy that enables the sequential ligations of widely available carboxylic acids and amines with fluorosulfuryl isocyanate (FSO 2 NCO) via a modular amidation/SuFEx (sulfur-fluoride exchange) process. This method provides facile access to chemical libraries of N-fluorosulfonyl amides (RCONHSO 2 F) and N-acylsulfamides (RCONHSO 2 NR'R'') in near-quantitative yields under simple and practical conditions. The robustness and efficiency of this double click strategy is showcased by the facile construction of chemical libraries in 96-well microtiter plates from a large number of carboxylic acids and amines. Preliminary biological activity screening reveals that some compounds exhibit high antimicrobial activities against Gram-positive bacterium S. aureus and drug-resistant MRSA (MIC up to 6.25 μg ⋅ mL -1 ). These results provide compelling evidence for the potential application of modular click chemistry library as an enabling technology in high-throughput medicinal chemistry., (© 2024 Wiley-VCH GmbH.)

Naturally occurring 6-pentyl-2H-pyran-2-one and its synthetic analogues greatly inhibit the settlement of Amphibalanus amphitrite cyprids and the growth and biofilm formation of marine bacteria. To optimize the antifouling activities of pyrone derivatives, this study designed pyrone analogues by modifying functional groups, such as the benzyl group, cyclopentane, and halides, substituted on both sides of a pyrone. The antifouling effects of the synthesized pyrone derivatives were subsequently evaluated against five marine biofilm-forming bacteria, Loktanella hongkongensis, Staphylococcus cohnii, S. saprophyticus, Photobacterium angustum, and Alteromonas macleodii, along with barnacle cyprids of Amphibalanus amphitrite. Substituting nonpolar parts-such as the aliphatic, cyclopentyl, or phenyl moieties on C-5 or the furan moieties on C-3-not only increased antibacterial activity and inhibited biofilm formation but also inhibited barnacle cyprid settlement when compared to 6-pentyl-2H-pyran-2-one., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Bacterial DNA gyrase and topoisomerase IV inhibition has emerged as a promising strategy for the cure of infections caused by antibiotic-resistant bacteria. The Novel Bacterial Topoisomerase Inhibitors (NBTIs) bind to a different site from that of the quinolones with novel mechanism of action. This evades the existing target-mediated bacterial resistance associated with quinolones. This article presents our efforts to identify in vitro potent and broad-spectrum antibacterial agent 4l., 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.)

Electrically conductive hydrogels (ECHs) combine the electrical properties of conductive materials with the unique features of hydrogels. They are attractive for various biomedical applications due to their smart response to electrical fields. Owing to their distinctive properties, such as biocompatibility, thermosensitivity and self-assembling behaviour, Pluronics can be adopted for the generation of hydrogels for biomedical applications. Here, innovative self-assembling ECHs holding antimicrobial properties for biomedical applications are developed, providing a full characterization of their macroscopic and microscopic properties. The rheological, morphological, and structural properties of Pluronic F68 (PF68) in the presence of conductive poly(3,4-ethylenedioxythiophene):poly-(styrenesulfonate) (PEDOT:PSS) are studied to optimize the synthesis of novel biocompatible and electrically conductive hydrogels. The addition of silver (Ag) flakes to the aqueous samples of PF68/PEDOT:PSS is used to further enhance the systems electrical conductivity and antimicrobial potency. Aqueous optimal samples with 45 wt% PF68 and different PEDOT:PSS/silver contents are investigated by means of experimental rheology and small-angle X-ray scattering (SAXS), to unveil the influence of both PEDOT:PSS and silver on the phase diagram, macroscopic flow properties, and morphology of the Pluronic-based systems. The presence of PEDOT:PSS and silver flakes endows Pluronic systems with high conductive properties, while preserving the same self-assembly features of PF68 in water. Moreover, the functionalisation with silver flakes confers antimicrobial properties to the ECHs, as demonstrated by growth inhibition of the multi-drug resistant bacterium Staphylococcus aureus. The use of PF68 in this work provides a novel route for the synthesis of innovative ECHs, whose functionalities such as self-assembling behaviour, biocompatibility, conductivity, and bioactivity may inspire future avenues in the biomedical field., 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., (Crown Copyright © 2024. Published by Elsevier Inc. All rights reserved.)

A number of new substances were included into the (5Z)-5-[(2-piperidinequinoline-3-yl)methyl]-2-chloroquinoline structural framework. The condensation process 2-chloroquinoline, which served as a crucial reagent in the reaction with 3-carbaldehydes to produce 2,4-thiazolidinedione, allowed for the production of 1,3-thiazolidine-2,4-dione. The newly developed substances were described by means of their reactions with halide compounds, particularly those pertaining to substituted N-alkylation. Elemental analysis, Fourier-transform infrared spectroscopy (FT-IR), and proton nuclear magnetic resonance spectroscopy ( 1 H NMR) were used to identify the chemical. Furthermore, the antibacterial activity of the produced compounds was evaluated in vitro against a range of pathogens, including Bacillus subtilis, and Escherichia coli. Moreover, docking experiments were conducted using the PDF enzyme of E. coli to improve our understanding of the binding mechanism between the synthesized 5(A-N) compounds and the enzyme., 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.)

Food safety is closely related to human health and has become a worldwide, pressing concern. Food safety analysis is essential for ensuring food safety. Sulfur quantum dots (SQDs), a new type of zero-dimensional metal-free nanomaterials, have recently become the focus of scientific research due to their good luminescence properties, dispersibility, biocompatibility, and inherent antibacterial properties. This review focuses on recent advances in SQDs, with emphasis on their practical applications in the food field. First, commonly used methods for the synthesis of SQDs are presented, including traditional and emerging strategies. The properties of SQDs are then analyzed in detail, particularly their luminescence properties, catalytic activities, and reducing properties. Next, the use of SQDs in food safety detection and antibacterial fields are elaborated. Finally, this review discusses the challenges associated with the use of SQDs in food safety detection and antimicrobial applications., 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.)

Methicillin-resistant Staphylococcus aureus (MRSA) is one of the most common multi-resistant organisms found in hospital-acquired infections and is associated with high morbidity and mortality. The development of new drugs and promising therapeutic strategies against MRSA is thus an urgent request. In recent years, some natural products have been demonstrated to show great potential in improving the efficacy of antibiotics to treat various drug-resistant bacteria, particularly MRSA. In this context, we aimed to analyze systematically from the prior arts that investigated the synergy between natural products and antibiotics against MRSA. These findings not only give us a better understanding on the mechanism of actions but also shed light on the bioactive molecular scaffolds identified from diverse natural products. In the present study, we concentratedly reviewed the studies that utilized natural products to enhance the potency of conventional antibiotics against MRSA in the last decade. The timely information reported herein may give meaningful insights into the molecular design of novel and potent antibacterial agents and/or effective therapeutics to combat MRSA for practical applications., 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 misuse of antibiotics has led to an alarming increase in bacterial strains resistant to these drugs. Efflux pumps, which expel antibiotics from bacterial cells, have emerged as one of the key mechanisms of bacterial resistance. In the quest to combat and mitigate bacterial resistance, researchers have turned their attention to efflux pump inhibitors as a potential solution. Meldrum's acid, a synthetic molecule widely utilized in the synthesis of bioactive compounds, has garnered significant interest in this regard. Hence, this study aims to investigate the antibacterial activity and evaluate the efficacy of three derivatives of meldrum's acid in inhibiting efflux mechanisms, employing both in silico and in vitro approaches. The antibacterial activity of the derivatives was assessed through rigorous broth microdilution testing. While the derivatives themselves did not exhibit direct antibacterial activity, they demonstrated remarkable potential in potentiating the effects of antibiotics. Additionally, fluorescence emission assays using ethidium bromide (EtBr) revealed fluorescence levels comparable to the positive control, indicating a possible blockade of efflux pumps. Molecular docking studies conducted in silico further supported these findings by revealing binding interactions similar to norfloxacin and CCCP, known efflux pump inhibitors. These results underscore the potential of meldrum's acid derivatives as effective inhibitors of efflux pumps. By inhibiting these mechanisms, the derivatives hold promise in enhancing the effectiveness of antibiotics and combatting bacterial resistance. This study contributes valuable insights into the development of novel strategies to address the pressing issue of bacterial resistance and paves the way for further research and exploration in this field., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financialinterestsor personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The emergence of multidrug-resistant bacterial have caused severe burden for public health. Particularly, Staphylococcus aureus as one of ESKAPE pathogens have induced various infectious diseases and resulted in increasing deaths. Developing new antibacterial agents is still urgent and challenging. Fortunately, in this study, based on aggregation-induced emission (AIE) ruthenium complexes were designed and synthesized, which realized the high efficiency of reactive oxygen species generation and remarkably killed S. aureus unlike conventional antibiotics action. Significantly, owing to good singlet oxygen production ability, Ru1 at only 4 μg/mL of concentration displayed good antibacterial photodynamic therapy effect upon white light irradiation and could deplete essential coenzyme NADH to disrupt intracellular redox balance. Also, the electrostatic interaction between Ru1 and bacteria enhanced the possibility of antibacterial. Under light irradiation, Ru1 could efficiently inhibit the biofilm growth and avoid the development of drug-resistant. Furthermore, Ru1 possessed excellent biocompatibility and displayed remarkable therapy effect in treating mice-wound infections in vivo. These findings indicated that AIE-based ruthenium complexes as new antibacterial agent had great potential in photodynamic therapy of bacteria and addressing the drug-resistance crisis., Competing Interests: Declaration of competing interest There are no conflicts to declare., (Copyright © 2024. Published by Elsevier Inc.)

The novel non-peripheral octa-substituted zinc(II) phthalocyanines with 3- and 4-pyridinepropoxy substituents were synthesized via cyclization of substituted phthalonitriles and further characterized. Their photodynamic and sonodynamic activity were then assessed toward bacteria and cancer cells. Additionally, inhibition activity against common human enzymes was evaluated. The singlet oxygen generation (with 1,3-diphenylisobenzofuran - DPBF as an unspecific chemical quencher of singlet oxygen) were measured under light irradiation, whereas under ultrasounds (1 MHz, 3 W) the stability of DPBF in the presence of sensitizer was evaluated. Both phthalocyanines revealed high photostability in DMSO and moderate in DMF, whereas the sonostability in DMF was moderate. Calculated light-induced singlet oxygen generation quantum yields were similar for both compounds and oscillated around 0.33 in DMF and 0.67 in DMSO. Sonodynamic manner revealed moderately high DPBF decomposition upon 1 MHz. Significant bacterial reduction was noted in both photodynamic and sonodynamic manner, reaching >3 log reduction against MRSA and S. epidermidis. Both compounds showed ca. 50 % viability reduction toward hypopharyngeal tumor (FaDu). Moreover, up to 60 % viability reduction was observed in squamous cell carcinoma (SCC-25). In summary, this molecular building of the efficient phthalocyanine-based sensitizer is a potential therapeutic for photodynamic and sonodynamic applications., 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 Inc. All rights reserved.)

New silver(I) complexes of 5-(trifluoromethyl)uracil (5TFMU) and 6-(trifluoromethyl)uracil (6TFMU) isomers were synthesized, characterized, and evaluated as antibacterial and antiproliferative agents. Based on elemental and thermogravimetric analyses, the Ag-5TFMU and Ag-6TFMU species are formulated as AgC 5 H 2 F 3 N 2 O 2 and Ag 2 C 5 HF 3 N 2 O 2 , respectively. Infrared and 13 C solid-state nuclear magnetic resonance spectroscopies suggest coordination of the trifluoromethyluracil isomers to silver by both nitrogen and oxygen atoms. Confirmation of their structure and connectivity was achieved, in the absence of single crystals of suitable quality, by state-of-the-art structural powder diffraction methods. In Ag-5TFMU, the organic ligand is tridentate and two distinct metal coordination environments are found (linear AgN 2 as well as C 2v AgO 4 geometries), whereas Ag-6TFMU contains a complex polymeric structure with tetradentate dianionic 6TFMU moieties and five distinct AgX 2 (X = N, O) fragments, further stabilized by ancillary (longer) Ag … O contacts. These species presented modest activity over Gram-positive and Gram-negative bacterial strains, whereas Ag-6TFMU was active over a set of tumor cells, with the best activity over prostate (PC-3) and kidney cell lines and selectivity indices of 4.6 and 1.3, respectively. On the other hand, Ag-5TFMU was active over all considered tumor cells except MCF-7 (breast cancer). The best activity was found for PC-3 cells, but no selectivity was observed. The Ag-5TFMU and Ag-6TFMU species also reduced the proliferation of tongue squamous cell carcinoma cell lines SCC - 4 and SCC-15. Preliminary biophysical assays by circular dichroism suggest that the Ag-5TFMU complex interacts with DNA by intercalation, an effect not seen in Ag-6TFMU., Competing Interests: Declaration of competing interest No potential conflict of interest was reported by the authors., (Copyright © 2024 Elsevier Inc. All rights reserved.)

The synthesis and spectroscopic characterization of three complexes containing a substituted 2-(2-pyridyl)benzothiazole (PyBTh) group in the ligand frame are reported along with the comparative biological activity. The ligands have been substituted at the 6-position with either a methoxy (Py(OMe)BTh) or a methyl group (Py(Me)BTh). Reaction of Py(OMe)BTh with either CuCl 2 or Cu(NO 3 ) 2 ·2.5 H 2 O yielded the monomeric [Cu(Py(OMe)BTh)) 2 (NO 3 )]NO 3 ·1.5 MeOH, (1·1.5 MeOH) complex or the dimeric [Cu(Py(OMe)BTh)Cl 2 ] 2 (2), respectively, with the nuclearity of the complex dependent on the starting Cu(II) salt. Reaction between the methyl substituted ligand and Cu(NO 3 ) 2 ·2.5 H 2 O resulted in the isolation of Cu(Py(Me)BTh)(NO 3 ) 2 ·0.5 THF (3·0.5 THF). Complexes 1-3 were fully characterized. Cyclic voltammetry measurements were performed on all three complexes as well as on [Cu(PyBTh) 2 (H 2 O)](BF 4 ) 2 (4), a compound previously reported by us which contains the unsubstituted 2-(2-pyridyl)benzothiazole ligand. The biological activity was studied and included concentration dependent DNA binding and cleavage, antibacterial activity, and cancer cell toxicity. All complexes exhibited DNA cleavage activity, however 2 and 4 were found to be the most potent. Mechanistic studies revealed that the nuclease activity is dependent on an oxidative mechanism reliant principally on O 2 - . Antibacterial studies revealed complex 4 was more potent compared to 1-3. Cancer cell toxicity studies were carried out on HeLa, PC-3, and MCF7 cells with 1-4, Cu(QBTh)(NO 3 ) 2 (H 2 O) and Cu(PyBIm) 3 (BF 4 ) 2 . The differences in the observed toxicities suggests the importance of the ligand and its substituents in modulating cell death., 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.)

Bacterial infections have become a major global public health issue, particularly with the emergence of multidrug-resistant strains. Therefore, developing non-antibiotic antimicrobial agents is crucial for treating drug-resistant bacterial infections. Building on previous research into natural products as novel antibacterial agents, this study synthesized curcumin-derived carbon dots using curcumin and ethylenediamine as raw materials through a hydrothermal method. The resulting carbon dots not only improved the water solubility and stability of curcumin but also exhibited highly efficient broad-spectrum antibacterial activity. Detailed investigations into the antibacterial performance and mechanisms of the carbon dots were conducted through experiments such as minimum inhibitory concentration (MIC) determination, live/dead bacterial staining, morphological studies, nucleic acid concentration detection, and reactive oxygen species (ROS) detection. The results indicated that the carbon dots significantly damaged the structural integrity of bacteria and generated large amounts of ROS. They exhibited remarkable antibacterial effects against Escherichia coli, Pseudomonas aeruginosa, and Staphylococcus aureus, and effectively inhibited drug-resistant MRSA. Their antibacterial efficacy was notably superior to that of broad-spectrum antibiotics such as chloramphenicol and Sulfadiazine. This study highlights the potential application of curcumin-derived carbon dots in combating bacterial infections and provides valuable insights for developing novel antibacterial agents derived from natural 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 Elsevier B.V. All rights reserved.)

Peptides have attracted great interest as platforms for the design of nanocomposite hydrogels due to their distinct bioactivity, biofunctionality and biocompatibility. Previously, we have reported on a family of peptides that self-assembled to form stabilised three-dimensional hydrogel networks, displaying potent antimicrobial activity. In this paper, we report on the use of these hydrogelator sequences and their analogues as stabilisers and growth controllers to synthesise anisotropic gold nanoparticles (AuNPs) of different sizes and shapes. In particular, hollow spherical nanoparticles were obtained for HG2.81-AuNPs, whereas hexagonal nanoparticles were observed for TOH&#95;1N-AuNPs and PentaOH-AuNPs in their respective hydrogel networks. The PentaOH-AuNPs' hydrogel exhibited excellent results with high antimicrobial potency against Staphylococcus aureus and Pseudomonas aeruginosa ATCC 27853 and negligible cytotoxicity. On the other hand, TOH&#95;1N-AuNPs showed no antibacterial activity and no cytotoxicity, demonstrating the versatility of these peptides. This work gives credence towards the development of these materials towards further applications such as in tissue culture technology and wound dressing materials., (© 2024 The Author(s). Journal of Peptide Science published by European Peptide Society and John Wiley & Sons Ltd.)

In the present report, we have described the synthesis of N-aminopolyhydroquinoline (N-PHQ) derivatives using highly efficient β -cyclodextrin ( β -CD) as a catalyst by the Hantzsch condensation of substituted aromatic aldehydes, dimedone, and hydrazine hydrate in one pot. The reactions were completed in a shorter time without the generation of any other byproduct. The synthesized N-PHQs were washed thoroughly with distilled water and recrystallized with ethanol to get highly purified products (as crystals). The structure of the synthesized N-PHQs was established by using advanced spectroscopic techniques like FT-IR, NMR ( 1 H, 13 C, DEPT, COSY, and HSQC), ESI-MS, and Elemental Analyzer. The N-PHQs derivatives demonstrated moderate to excellent resistance against the tested strains (both fungal as well as bacterial). The presence of polar groups, which are able to form H-bonds, attached to the phenyl ring like -NO 2 ( 4b and 4c) , and -OMe ( 4i, 4j, and 4k ) exhibits excellent activity, which is comparable to standard drugs, amoxicillin and fluconazole.

A multifunctional polyoxometalate-ionic liquid (POM-IL)-based hybrid material comprising silicotungstic acid, [BmIm] 4 [SiW 12 O 40 ], has been synthesized and demonstrated its efficiency toward methylene blue removal and as an antibacterial agent. Single-crystal XRD analysis confirms that the material crystallizes in monoclinic symmetry (SG: Pn ), with lattice parameters a = 13.1396(5) Å, b = 16.9655(8) Å, c = 14.3493(7) Å, and Z = 2. The structure comprises a single polyanionic [SiW 12 O 40 ] 4- moiety surrounded by four cationic [BmIm] + units of two different conformations, which supported DFT and Hirshfeld surface analysis. The material shows excellent removal efficiency for methylene blue, with a maximum adsorption capacity of 92.47 mg/g and 83.05% reusability after five cycles. On the contrary, FTIR and ζ-potential analyses confirm that electrostatic interactions are the predominant factors governing the adsorption process. The material also acts as a superior antibacterial agent against the opportunistic pathogens Pseudomonas aeruginosa , Klebsiella pneumoniae , and Escherichia coli with a MIC of 500-700 μg/mL. However, a comparative assessment showed that the material was more effective against P. aeruginosa compared to the other two pathogens. PXRD analysis confirms the phase purity, and FESEM and TEM analyses exhibit block-shaped morphology with particle sizes ∼2-3 μm.

Titanium dioxide nanoparticles, renowned for their abundance, non-toxicity, and stability, have emerged as indispensable components in various fields such as air purification, healthcare, and industrial processes. Their applications as photocatalysts and antibacterial agents are particularly prominent. The synthesis methods significantly influence the properties and subsequent applications of these nanoparticles. While several techniques exist, the biological approach using plant extracts offers advantages such as simplicity, biocompatibility, and cost-effectiveness. This study focused on the green synthesis of titanium dioxide nanoparticles utilizing spinach leaf extract. Within the scope of this investigation, the green synthesis of titanium dioxide nanoparticles through spinach leaf extract were synthesized and optimized, followed by a comprehensive examination of their morphological, structural, and chemical attributes with UV-visible spectroscopy, FTIR spectroscopy, XRD, FESEM, and EDX. The minimum inhibitory concentration (MIC) against E. coli and S. aureus was determined to evaluate their antibacterial potential. Optimal synthesis conditions were identified at 50 °C, using a 1/30 concentration and 20 ml of spinach leaf extract. Spherical anatase nanoparticles, ranging from 10 to 40 nm, were produced under these conditions. The change in the color of the extract, absorption at 247 nm, change and increase of the peak at 800 - 400 wavelengths, and the maximum intensity of X-ray diffraction at the angle of 25.367 with the crystal plane 101 were indications of the synthesis of these nanoparticles. Notably, the synthesized nanoparticles exhibited antibacterial activity with MIC values of 0.5 mg/ml against E. coli and 2 mg/ml against S. aureus. This research presents a novel, eco-friendly approach to synthesizing titanium dioxide nanoparticles with promising antibacterial properties., (© 2024. The Author(s).)

The revised structure, 2 , assigned to the title natural product has been prepared by chemical synthesis using a reaction sequence involving six simple steps starting from 2,3-dimethoxybenzaldehyde and proceeding via intermediates 8 , 12 , and 14 . A comparison of the NMR data acquired on synthetically derived compound 2 with those reported for the natural product reveals an excellent match. Preliminary biological screening of compound 2 along with analogues/precursors 7 , 9 , 10 , 11 , 13 , 14 , and 15 revealed that none exhibited antibacterial, antifungal or cytotoxic effects.

The biofilm formation of Pseudomonas aeruginosa involves multiple complex regulatory pathways; thus, blocking a single pathway is unlikely to achieve the desired antibiofilm efficacy. Herein, a series of hybrids of 3-hydroxypyridin-4(1 H )-ones and long-chain 4-aminoquinolines were synthesized as biofilm inhibitors against P. aeruginosa based on a multipathway antibiofilm strategy. Comprehensive structure-activity relationship studies identified compound 30b as the most valuable antagonist, which significantly inhibited P. aeruginosa biofilm formation (IC 50 = 5.8 μM) and various virulence phenotypes. Mechanistic studies revealed that 30b not only targets the three quorum sensing systems but also strongly induces iron deficiency signals in P. aeruginosa . Furthermore, 30b demonstrated a favorable in vitro and in vivo safety profile. Moreover, 30b specifically enhanced the antibacterial activity of tobramycin and polymyxin B in in vitro and in vivo combination therapy. Overall, these results highlight the potential of 30b as a novel anti-infective candidate for treating P. aeruginosa infections.

Antibiotic resistance is a major global health threat, necessitating the development of new treatments and diverse molecules to combat severe infections and preserve the efficacy of existing drugs. Antimicrobial peptides (AMPs) offer a versatile arsenal against bacteria, and peptide structure branching can enhance their resistance to proteases and improve their overall efficacy. A small library of peptides derived from natural host defense peptides and synthesized in a tetrabranched form was selected against E. coli . Six selected branched peptides were further studied for antibacterial activity against a panel of strains, biofilm inhibition, protease resistance, and cytotoxicity. Their structure was predicted computationally and their mechanism of action was investigated by electron microscopy and by using fluorescent dyes. The peptide BAMP2 showed promise in a mouse skin infection model, indicating the potential for local infection treatment.

Infections with methicillin-resistant Staphylococcus aureus (MRSA) are becoming increasingly serious, making the development of novel antimicrobials urgent. Here, we synthesized some amphiphilic honokiol derivatives bearing an oxazole moiety and investigated their antibacterial and hemolytic activities. Bioactivity evaluation showed that E17 possessed significant in vitro antibacterial activity against S. aureus and MRSA, along with low hemolytic activity. Moreover, E17 exhibited rapid bactericidal properties and was not susceptible to resistance. Mechanistic studies indicated that E17 interacts with phosphatidylglycerol and cardiolipin of bacterial cell membranes, leading to changes in cell membrane permeability and polarization, increased intracellular ROS, and leakage of DNA and proteins, thus accelerating bacterial death. Transcriptome analysis further demonstrated that E17 has membrane-targeting effects, affecting the expression of genes related to cell membranes and ABC transporter proteins. Notably, in vivo activity showed that E17 has prominent anti-MRSA efficacy, comparable to vancomycin, and is expected to be a new anti-MRSA drug candidate.

Herein, we developed a series of benzo[1,3]oxazinyloxazolidinones as potent antibacterial agents. Some of the compounds exhibited potent antibacterial activity against a range of clinical drug-resistant pathogens, including Mtb, MRSA, MRSE, VISA, and VRE. Notably, compound 16d inhibited protein synthesis and displayed potent activity against linezolid-resistant Enterococcus faecalis . Although 16d showed cross-resistance to linezolid-resistant MRSA, the frequency of resistance development of MRSA against 16d was lower compared to that of linezolid. Additionally, 16d exhibited excellent pharmacokinetic properties and superior in vivo efficacy compared to linezolid. Furthermore, compound 16d modulated cytokine levels and ameliorated histopathological changes in major organs of bacterially infected mice. Hoechst-PI double staining and scanning electron microscopy analyses revealed that 16d exhibited some similarities with linezolid in its effects while also demonstrating a distinct mechanism characterized by cell membrane damage. Moreover, 16d significantly disrupted the MRSA biofilms. The antibacterial agent 16d represents a promising candidate for the treatment of serious infections caused by drug-resistant bacteria.

Bacterial RNA polymerase (RNAP), the core enzyme responsible for bacterial transcription, requires the NusG factor for efficient transcription elongation and termination. As the primary binding site for NusG, the RNAP clamp-helix (CH) domain represents a potential protein-protein interaction (PPI) target for novel antimicrobial agent design and discovery. In this study, we designed a pharmacophore model based on the essential amino acids of the CH for binding to NusG, such as R270, R278, and R281 ( Escherichia coli numbering), and identified a hit compound with mild antimicrobial activity. Subsequent rational design and synthesis of this hit compound led to improved antimicrobial activity against Streptococcus pneumoniae , with the minimum inhibitory concentration (MIC) reduced from 128 to 1 μg/mL. Additional characterization of the antimicrobial activity, inhibitory activity against RNAP-NusG interaction, and cell-based transcription and fluorescent assays of the optimized compounds demonstrated their potential for further lead optimization.

The incidence of Mycobacterium marinum infection is on the rise; however, the existing drug treatment cycle is lengthy and often requires multi-drug combination. Therefore, there is a need to develop new and effective anti- M. marinum drugs. Cochliomycin A, a 14-membered resorcylic acid lactone with an acetonide group at C-5' and C-6', exhibits a wide range of antimicrobial, antimalarial, and antifouling activities. To further explore the effect of this structural change at C-5' and C-6' on this compound's activity, we synthesized a series of compounds with a structure similar to that of cochliomycin A, bearing ketal groups at C-5' and C-6'. The R / S configuration of the diastereoisomer at C-13' was further determined through an NOE correlation analysis of CH 3 or CH 2 at the derivative C-13' position and the H-5' and H-6' by means of a 1D NOE experiment. Further comparative 1 H NMR analysis of diastereoisomers showed the difference in the chemical shift ( δ ) value of the diastereoisomers. The synthetic compounds were screened for their anti-microbial activities in vitro. Compounds 15 - 24 and 28 - 35 demonstrated promising activity against M. marinum , with MIC 90 values ranging from 70 to 90 μM, closely approaching the MIC 90 of isoniazid. The preliminary structure-activity relationships showed that the ketal groups with aromatic rings at C-5' and C-6' could enhance the inhibition of M. marinum . Further study demonstrated that compounds 23 , 24 , 29 , and 30 had significant inhibitory effects on M. marinum and addictive effects with isoniazid and rifampicin. Its effective properties make it an important clue for future drug development toward combatting M. marinum resistance.

Antibiotics are currently used for the treatment of Helicobacter pylori ( H. pylori ), which is confirmed to be the major cause of gastric disorders. However, the long-term consumption of antibiotics has already caused antibiotic resistance and side effects in vivo. Therefore, there is an emerging need for searching for safe and effective anti- H. pylori agents. Inspired by the excellent bioactivities of cinnamic acid, a series of cinnamic acid derivatives (compounds 1 - 30 ) were synthesized and determined for H. pylori inhibition. The initial screening revealed that compound 23 , a 2,4-dinitro cinnamic acid derivative containing 4-methoxyphenol, showed excellent H. pylori inhibition with an MIC value of 4 μM. Further studies indicated that compound 23 showed anti-bacterial activity and had a bactericidal effect on H. pylori due to the destruction of the bacterial structure. Molecular docking analysis revealed that the 2,4-dinitro groups in cinnamic acid moiety formed hydrogen bonding with amino acid residues in an active pocket of H. pylori protein. Interestingly, the ester moiety fitted into the hydrophobic pocket, attaining additional stability to compound 23 . Above all, the present study reveals that compound 23 could be considered a promising anti- H. pylori agent to treat H. pylori causing gastritis.

This research adopted the Fischer indole synthesis method to continue constructing a novel drug-like chemical entity based on the guidance of isocryptolepine and obtained four series of derivatives: Y , Da , Db , and Dc . The antimicrobial activity of these derivatives against plant pathogens was further evaluated. The results showed that Dc-2 had the best antifungal effect against Botrytis cinerea , and its EC 50 value was up to 1.29 μg/mL. In addition, an in vivo activity test showed that the protective effect of Dc-2 on apples was 82.2% at 200 μg/mL, which was better than that of Pyrimethanil (45.4%). Meanwhile, it was found by scanning electron microscopy and transmission electron microscopy that the compound Dc-2 affected the morphology of mycelia. The compound Dc-2 was found to damage the cell membrane by PI and ROS staining. Through experiments such as leakage of cell contents, it was found that the compound Dc-2 changed the permeability of the cell membrane and caused the leakage of substances in the cell. According to the above studies, compound Dc-2 can be used as a candidate lead compound for further structural optimization and development.

The first total synthesis of the pentacyclic phenylnaphthacenoid type II polyketide antibiotic formicamycin H is described. A key feature of the synthesis involves the convergent, regioselective assembly of the tetracyclic core via ruthenium-catalyzed α-ketol-benzocyclobutenone [4 + 2] cycloaddition. Double dehydration of the diol-containing cycloadduct provides an achiral enone, which upon asymmetric nucleophilic epoxidation and further manipulations delivers the penultimate tetracyclic trichloride in enantiomerically enriched form. Subsequent chemo- and atroposelective Suzuki cross-coupling of the tetracyclic trichloride introduces the E-ring to complete the total synthesis. Single-crystal X-ray diffraction analyses of two model compounds suggest that the initially assigned stereochemistry of the axially chiral C6-C7 linkage may require revision.