Broad-spectrum Antimicrobial Activity Research Articles

Cinnamaldehyde in Focus: Antimicrobial Properties, Biosynthetic Pathway, and Industrial Applications

Trans-cinnamaldehyde (TCA), a major bioactive compound derived from cinnamon (Cinnamomum spp.), has garnered significant attention for its diverse therapeutic properties. Its broad-spectrum antimicrobial activity, targeting both Gram-positive and Gram-negative bacteria as well as various fungi, positions TCA as a potent natural antimicrobial agent. Beyond its antimicrobial effects, TCA demonstrates promising antidiabetic and anti-inflammatory activities, making it a valuable compound in medicinal and cosmetic applications. Recent studies have highlighted its role in disrupting microbial membranes, inhibiting biofilm formation, and modulating key metabolic pathways in pathogens. Furthermore, TCA has gained popularity in cosmetics due to its antimicrobial activity, antioxidant properties, and skin-friendly profile. This review provides a comprehensive overview of TCA’s antimicrobial potential, focusing on its mechanisms of action and its market and industrial applications. We also discuss the biosynthetic pathway of TCA, exploring both its natural production in cinnamon and advances in biotechnological production methods. As the demand for sustainable and natural antimicrobial agents grows, TCA emerges as a promising candidate for diverse applications. Finally, this review explores future directions for optimizing TCA production through metabolic engineering and synthetic biology approaches to meet industrial-scale demands.

Progress in the Identification and Design of Novel Antimicrobial Peptides Against Pathogenic Microorganisms

Abstract The occurrence and spread of antimicrobial resistance (AMR) pose a looming threat to human health around the world. Novel antibiotics are urgently needed to address the AMR crisis. In recent years, antimicrobial peptides (AMPs) have gained increasing attention as potential alternatives to conventional antibiotics due to their abundant sources, structural diversity, broad-spectrum antimicrobial activity, and ease of production. Given its significance, there has been a tremendous advancement in the research and development of AMPs. Numerous AMPs have been identified from various natural sources (e.g., plant, animal, human, microorganism) based on either well-established isolation or bioinformatic pipelines. Moreover, computer-assisted strategies (e.g., machine learning (ML) and deep learning (DL)) have emerged as a powerful and promising technology for the accurate prediction and design of new AMPs. It may overcome some of the shortcomings of traditional antibiotic discovery and contribute to the rapid development and translation of AMPs. In these cases, this review aims to appraise the latest advances in identifying and designing AMPs and their significant antimicrobial activities against a wide range of bacterial pathogens. The review also highlights the critical challenges in discovering and applying AMPs.

De Novo Design of Tryptophan Containing Broad-Spectrum Cationic Antimicrobial Octapeptides.

With the advent of antibiotic resistant organisms, development of alternate classes of molecules other than antibiotics to combat microbial infections, have become extremely important. In this context, antimicrobial peptides have taken center stage of antimicrobial therapeutic research. In this work, we have reported two cationic antimicrobial octapeptides WRL and LWRF, with broad spectrum antimicrobial activities against several strains of ESKAPE pathogens. Both the peptides were membrane associative and induced microbial cell death through membranolysis, being selective towards microbial membranes over mammalian membranes. The AMPs were unstructured in water, adopting partial helical conformation in the presence of microbial membrane mimics. Electrostatic interaction formed the primary basis of peptide-membrane interactions. WRL was more potent, salt tolerant and faster acting of the two AMPs, owing to the presence of two tryptophan residues against that of one in LWRF. Increased tryptophan number in WRL enhanced its membrane association ability, resulting in higher antimicrobial potency but lower selectivity. This experimental and computational work, established that an optimum number of tryptophan residues and their position was critical for obtaining high antimicrobial potency and selectivity simultaneously in the designed cationic AMPs. Understanding the peptide membrane interactions in atomistic details can lead to development of better antimicrobial therapeutics in future.

A small antimicrobial peptide derived from a Burkholderia bacterium exhibits a broad-spectrum and high inhibiting activities against crop diseases.

Crop diseases cause significant quality and yield losses to global crop products each year and are heavily controlled by chemicals along with very limited antibiotics composed of small molecules. However, these methods often result in environmental pollution and pest resistance, necessitating the development of new bio-controlling products to mitigate these hazards. To identify effective antimicrobial peptides (AMPs) considered as potential sources of future antibiotics, AMPs were screened from five bacterial strains showing antagonism against a representative phytopathogenic fungus (Rhizoctonia Solani) through the Bacillus subtilis expression system, which has been developed for identifying bacterial AMPs by displaying autolysis morphologies. A total of 5000 colonies were screened, and five displaying autolysis morphologies showed antagonism against R. solani. A novel AMP with the strongest antagonism efficiency was determined and tentatively named HR2-7, which is composed of 24 amino acids with an alpha-helical structure. HR2-7 has strong and broad-spectrum antimicrobial activity, tested against 10 g-positive and -negative bacteria and four phytopathogenic fungi by contact culture in plates with minimal lethal concentrations of 4.0 μM. When applied as purified peptide or in fermented B. subtilis culture solution, HR2-7 showed strong controlling efficiency on plants against diverse fungal and bacterial pathogens. Based on current understanding, HR2-7 is recognized as the first AMP derived from an agricultural antagonistic bacterium. It exhibits wide-ranging and notable antimicrobial efficacy, offering a supplementary approach for managing plant diseases, in addition to conventional chemical pesticides and antibiotics.

Investigation of the Mechanism of Action of AMPs from Amphibians to Identify Bacterial Protein Targets for Therapeutic Applications

Antimicrobial peptides (AMPs) from amphibians represent a promising source of novel antibacterial agents due to their potent and broad-spectrum antimicrobial activity, which positions them as valid alternatives to conventional antibiotics. This review provides a comprehensive analysis of the mechanisms through which amphibian-derived AMPs exert their effects against bacterial pathogens. We focus on the identification of bacterial protein targets implicated in the action of these peptides and on biological processes altered by the effect of AMPs. By examining recent advances in countering multidrug-resistant bacteria through multi-omics approaches, we elucidate how AMPs interact with bacterial membranes, enter bacterial cells, and target a specific protein. We discuss the implications of these interactions in developing targeted therapies and overcoming antibiotic resistance (ABR). This review aims to integrate the current knowledge on AMPs’ mechanisms, identify gaps in our understanding, and propose future directions for research to harness amphibian AMPs in clinical applications.

Randomized Clinical Trials Demonstrate the Safety Assessment of Alkalihalobacillus clausii AO1125 for Use as a Probiotic in Humans

(1) Background: Alkalihalobacillus clausii AO1125 is a Gram-positive, motile, spore-forming bacterium with potential as a probiotic due to its broad-spectrum antimicrobial activity, inhibiting pathogens like Listeria monocytogenes, Staphylococcus aureus, and Clostridium difficile, as well as anti-rotavirus activity. Its resilience in gastrointestinal conditions suggests benefits for gut health. This study evaluates the safety and probiotic potential of A. clausii AO1125. (2) Methods: Genome annotation identified genes linked to probiotic traits such as stress resistance, gut colonization, immune modulation, and antimicrobial production. The genome was screened for antibiotic resistance genes using CARD, bacteriocin clusters using BAGEL4, and virulence factors via VFDB. Cytotoxicity was assessed on Vero cells and erythrocytes, and a Phase I, double-blind, placebo-controlled clinical trial was conducted with 99 healthy volunteers (50 AO1125, 49 placebo). (3) Results: Genomic analysis confirmed minimal antibiotic resistance genes and the absence of virulence factors, supporting safety. A. clausii AO1125 showed no pathogenicity, cytotoxicity, or hemolytic activity and was well-tolerated in clinical settings, with mild, transient abdominal gas as the most common adverse event. (4) Conclusions: The safety profile and genetic basis for probiotic and antimicrobial properties support A. clausii AO1125 as a promising probiotic candidate for gastrointestinal health, warranting further clinical research.

Antimicrobial Peptides: A Promising Alternative to Conventional Antimicrobials for Combating Polymicrobial Biofilms.

Polymicrobial biofilms adhere to surfaces and enhance pathogen resistance to conventional treatments, significantly contributing to chronic infections in the respiratory tract, oral cavity, chronic wounds, and on medical devices. This review examines antimicrobial peptides (AMPs) as a promising alternative to traditional antibiotics for treating biofilm-associated infections. AMPs, which can be produced as part of the innate immune response or synthesized therapeutically, have broad-spectrum antimicrobial activity, often disrupting microbial cell membranes and causing cell death. Many specifically target negatively charged bacterial membranes, unlike host cell membranes. Research shows AMPs effectively inhibit and disrupt polymicrobial biofilms and can enhance conventional antibiotics' efficacy. Preclinical and clinical research is advancing, with animal studies and clinical trials showing promise against multidrug-resistant bacteria and fungi. Numerous patents indicate increasing interest in AMPs. However, challenges such as peptide stability, potential cytotoxicity, and high production costs must be addressed. Ongoing research focuses on optimizing AMP structures, enhancing stability, and developing cost-effective production methods. In summary, AMPs offer a novel approach to combating biofilm-associated infections, with their unique mechanisms and synergistic potential with existing antibiotics positioning them as promising candidates for future treatments.

A novel antimicrobial peptide CpAMP identified from Chinese horseshoe crab, Tachypleus tridentatus.

Antibacterial peptide (AMP) is a crucial component of the innate immune system in most organism, play an important role in host defense processes. Many of these peptides have broad antimicrobial activity against Gram-negative, -positive bacteria and fungi. In the present study, a novel AMP named CpAMP was identified using transcriptome analysis in Chinese horseshoe crab. The preprotein of CpAMP consists of a signal peptide (21 aa) and a mature peptide (47 aa) enriched by cysteine. And the putative mature peptide CpAMP was 4.95 kDa with a theoretical isoelectric point (pI) of 8.73. The mature CpAMP showed α-helix and irregularly curled structure in the cys-stabilized region. CpAMP exhibited a broad spectrum of antimicrobial activity against Gram-negative, -positive bacteria and antibiotic-resistant strains. In addition, CpAMP can significantly increase the survival rate of zebrafish infected with bacteria. Due to its broad-spectrum antibacterial activity and the sensitivity of drug-resistant strains, CpAMP could be used as a new type of drug for inhibition of pathogenic microorganisms or as an immune enhancer in animals.

Functional interplay between short antimicrobial peptides and model lipid membranes

Antimicrobial peptides (AMPs) are considered an attractive generation of novel antibiotics due to their advantageous properties such as a broad spectrum of antimicrobial activity against pathogens, low cytotoxicity, and drug resistance. Although they have common structural features and it has been widely demonstrated that bacterial membranes represent the main target of the peptide activity, the exact mechanism underlying the membrane perturbation by AMPs is not fully understood. Nevertheless, all the proposed modes of action implicate the preliminary interaction of AMPs with the negatively charged lipids in bacterial membranes. Recently, the structural and functional characterization of two AMPs, RiLK1 and RiLK3, was reported. Specifically, both peptides were revealed to be multitalented compounds capable of binding Gram-positive and Gram-negative liposome models with high affinity, but their mechanism of action remains elusive. In this paper, the effects of RiLK1 and RiLK3 on vesicles mimicking prokaryotic and eukaryotic cell membranes were further examined by using different approaches. Fluorescence and quenching assays either by acrylamide or lipophilic probes suggested that the peptides were mainly located at the interface of the negatively charged membranes that mimicked those of Salmonella Typhimurium and Staphylococcus aureus, possibly oriented in a parallel manner. Furthermore, RiLK1 and RiLK3 caused a significant leakage of carboxyfluorescein from bacterial liposomes, demonstrating that they can permeabilize the target membranes at high doses. Conversely, both peptides appear to behave like cell penetrating peptides (CPPs) at concentrations near their MIC values evaluated against the bacterial targets. Moreover, Dynamic Light Scattering provided further insights on the mechanisms of antimicrobial peptide against the bacterial liposomes. Conclusively, in vitro experiments indicated that RiLK1 and RiLK3 displayed potent bacteriostatic efficacy at low micromolar concentrations against an antibiotic-resistant ESKAPE pathogen, making them a valuable tool in preventing and treating infections caused by such bacteria.

Design, microwave synthesis, characterization and antimicrobial activity of imidazolone derivatives

Overuse and misuse of antibiotics create superbugs as drug-resistant bacteria. The vital strategy is developing new antibiotics, and one of the vital compounds that proved activity as antimicrobials is imidazoles. So, we designed and synthesized a series of imidazolones via microwave radiation in excellent yield and evaluated them as antimicrobial agents with docking studies to promote and boost their activity. The results obtained from spectroscopic analyses approved the chemical structures of new compounds. The biological antimicrobial activity results was found that these compounds exert an excellent broad spectrum antimicrobial activity against many Gram-positive and Gram-negative bacteria, as well as different fungal strain including some highly human pathogenic microorganisms.Compounds 5a-5c are active against Gram-positive bacteria and compounds 5d-5f against Gram-negative bacteria, together with Candida albicans as fungi. Molecular Docking study on the active compounds 5e, 5f showed ring-stacking interactions between them as ligands and related proteins, which are compatible with other results. Gaussian 09 program is used as computational chemistry software to confirm the obtained experimental results.

One-step construction of silver nanoparticles immersed hydrogels by triple-helix β-glucans and the application in infectious wound healing

Hydrogels composed of polysaccharides and silver nanoparticles (AgNPs) are widely recognized for their application in wound dressings, particularly for healing wounds prone to infection. Traditional methods for preparing AgNP-immersed hydrogels are often complex, costly, and may lead to sustained cytotoxicity. To address these challenges, we developed a biocompatible, one-step green reduction strategy to generate AgNPs within hydrogels using a triple-helix β-glucan (PCPA) derived from Poria cocos, a renowned Chinese traditional herb. PCPA serves as a reducing agent, converting silver ions into AgNPs while its triple-helix conformation prevents AgNP aggregation. The resulting hydrogel (PAg-G) is injectable and contains uniformly distributed AgNPs. PAg-G exhibits broad-spectrum antimicrobial activity and enhanced bioactivity. The in vivo studies on S.aureus-infected SD rats demonstrated that PAg-G accelerates wound healing within 12 days by down-regulating inflammatory factors such as IL-6 and TNF-α, and up-regulating VEGF and CD31 expression, promoting neovascularization in wound tissues. This innovative one-step construction of AgNP-immersed hydrogels offers a promising approach for the development of antimicrobial hydrogels, especially for treating bacterial-infected wounds.

Mussel-like polydopamine-assisted aggregation-induced emission nanodot for enhanced broad-spectrum antimicrobial activity: In vitro and in vivo validation

Emerging luminogens with aggregation-induced emission properties, namely AIEgens, demonstrated excellent anti-bacteria activity potential. However, their application still limited by the low antibacterial activity caused by the poor binding with bacteria. Polydopamine (PDA), an important biological macromolecule, possesses superior adhesion ability toward various material surface, including bacteria. In this study, the novel mussel-like PDA-assisted AIE Nanodot was proposed, achieving with robust bacterial binding ability and enhanced broad-spectrum antibacterial activity. Binding ability inherited from the PDA enables the constructed PDA-assisted AIE Nanodot to adhere efficiently to the bacterial membrane surface. Meanwhile, the AIE properties endowed them with monitoring capability, allowing for tracking their interaction with bacteria through facile fluorescence imaging in real time. More importantly, excellent killing of both Gram-positive and Gram-negative bacteria were successfully achieved in vitro antibacterial tests with excellent biocompatibility. Furthermore, in the treatment of Methicillin-resistant S. aureus (MRSA)-infected mouse-wound model, the mice exhibited accelerated wound healing with low bacterial load. This novel integrated strategy introduced a simple but effectively design to enhance the binding and antibacterial ability of AIEgens and would diversify the existing pool of antibacterial agents.

Production of bacteriocin-like inhibitory substance (BLIS) by Staphylococcus spp. isolates from dogs.

In the present study, 39 canine isolates of Staphylococcus spp. were tested for antimicrobial substance (AMS) production. Seven AMS producers were identified, whose products exhibited a non-acidic character and a proteinaceous nature, therefore being considered bacteriocin-like inhibitory substances (BLIS). The producer strains of BLIS P1, P16 and I3 showed a broad spectrum of antimicrobial activity. Human, veterinary and plant pathogens, such as Listeria monocytogenes, Klebsiella pneumoniae, Staphylococcus spp. and Clavibacter michiganensis, were among the inhibited micro-organisms, suggesting the potential biotechnological application of these peptides. MALDI-TOF mass spectrometry and 16S rDNA sequencing identified the producer strains of BLIS P1, P16 and I3 as Staphylococcus pseudintermedius P1, Staphylococcus schleiferi P16 and Staphylococcus pseudintermedius I3. The plasmid profile of these strains suggests that the BLIS production is linked to biosynthetic genes located on plasmids. PCR analyses revealed that BLIS P1, P16 and I3 are different from 11 staphylococcins already described in the literature and that their genomic DNAs do not carry the most prevalent staphylococcal enterotoxin genes. The highest levels of BLIS production were achieved after 18-24h of growth of the producer strains in TSB medium. Moreover, BLIS P1 and I3 exhibited high resistance to temperature and pH variations, and BLIS P16 maintained 100% of its activity in almost all conditions tested. The characteristics associated with BLIS P1, P16 and I3 described in this work encourage further investigation of these substances, in addition to this study being the first report of BLIS production by a strain of S. schleiferi.

ISOLATION AND MOLECULAR IDENTIFICATION OF INDIGENOUS BACTERIOCIN-PRODUCING WEISSELLA CIBARIA

Globally, over 6.22 million deaths are associated with antibiotic resistance. Bacteriocins, a set of antimicrobial peptides synthesized on the ribosomes, are widely viewed as a potential answer to this issue. This is due to their pore-forming ability and antimicrobial activity against antibiotic-resistant pathogens. The aim of this study is to isolate bacteriocin-producing Weissella cibaria and evaluate its antimicrobial activity against Pseudomonas aeruginosa, Escherichia coli, Staphylococcus aureus, Klebsiella pneumoniae, Salmonella typhi, Proteus mirabilis, Streptococcus sp., Candida sp. and Rhizopus stolonifer. Weissella cibaria man1 was isolated by inoculating deMan Rogosa Sharpe (MRS) broth with small pieces of ripe Mangifera indica (mango), 24-hour incubation at 370C, 10-fold serial dilution and plating on MRS agar. Molecular identification was achieved by DNA extraction, amplification of the 16S rRNA gene through polymerase chain reaction (PCR), agarose gel electrophoresis, gene sequencing, and BLASTN homology searches in the National Center for Biotechnology Information (NCBI). Antimicrobial activity of the bacteriocin was determined by agar well diffusion assay. Mangifera indica (mango) was found to harbor bacteriocin-producing Weissella cibaria man1. The bacteriocin (weissellicin man1) exhibited a broad spectrum of antimicrobial activity. Weissellicin man1 suppressed the growth of several target pathogens (Pseudomonas aeruginosa, Klebsiella pneumoniae, Salmonella typhi, Proteus mirabilis, Candida sp. and Rhizopus stolonifer) but had no inhibitory action against Escherichia coli, Streptococcus sp., Staphylococcus aureus. In conclusion, weissellicin man1 from Weissella cibaria man1 has a broad-spectrum of antimicrobial action. These findings will facilitate further evaluation of the antimicrobial potency of weissellicin man1.

In-silico and in-vitro study of novel antimicrobial peptide AM1 from Aegle marmelos against drug-resistant Staphylococcus aureus

Antimicrobial peptides have garnered increasing attention as potential alternatives due to their broad-spectrum antimicrobial activity and low propensity for developing resistance. This is for the first time; proteome sequences of Aegle marmelos were subjected to in-silico digestion and AMP prediction were performed using DBAASP server. After screening the peptides on the basis of different physiochemical property, peptide sequence GKEAATKAIKEWGQPKSKITH (AM1) shows the maximum binding affinity with − 10.2 Kcal/mol in comparison with the standard drug (Trimethoprim) with − 7.4 kcal/mol and − 6.8 Kcal/mol for DHFR and SaTrmK enzyme respectively. Molecular dynamics simulation performed for 300ns, it has been found that peptide was able to stabilize the protein more effectively, analysed by RMSD, RMSF, and other statistical analysis. Free binding energy for DHFR and SaTrmK interaction from MMPBSA analysis with peptide was found to be -47.69 and − 44.32 Kcal/mol and for Trimethoprim to be -13.85 Kcal/mol and − 11.67 Kcal/mol respectively. Further in-vitro study was performed against Methicillin Susceptible Staphylococcus aureus (MSSA), Methicillin Resistant Staphylococcus aureus (MRSA), Multi-Drug Resistant Staphylococcus aureus (MDR-SA) strain, where MIC values found to be 2, 4, and 8.5 µg/ml lesser in comparison to trimethoprim which has higher MIC values 2.5, 5, and 9.5 µg/ml respectively. Thus, our study provides the insight for the further in-vivo study of the peptides against multi-drug resistant S. aureus.

The Antifungal Effects of Berberine and Its Proposed Mechanism of Action Through CYP51 Inhibition, as Predicted by Molecular Docking and Binding Analysis.

Fungal infections present a significant health risk, particularly in immunocompromised individuals. Berberine, a natural isoquinoline alkaloid, has demonstrated broad-spectrum antimicrobial activity, though its antifungal potential and underlying mechanisms against both yeast-like and filamentous fungi are not fully understood. This study investigates the antifungal efficacy of berberine against Candida albicans, Cryptococcus neoformans, Trichophyton rubrum, and Trichophyton mentagrophytes in vitro, as well as its therapeutic potential in a murine model of cryptococcal infection. Berberine showed strong antifungal activity, with MIC values ranging from 64 to 128 µg/mL. SEM and TEM analyses revealed that berberine induced notable disruptions to the cell wall and membrane in C. neoformans. No signs of cell necrosis or apoptosis were observed in fungal cells treated with 2 × MIC berberine, and it did not increase intracellular ROS levels or affect mitochondrial membrane potential. Molecular docking and binding affinity assays demonstrated a strong interaction between berberine and the fungal enzyme CYP51, with a dissociation constant (KD) of less than 1 × 10-12 M, suggesting potent inhibition of ergosterol biosynthesis. In vivo studies further showed that berberine promoted healing in guinea pigs infected with T. mentagrophytes, and in a murine cryptococcal infection model, it prolonged survival and reduced lung inflammation, showing comparable efficacy to fluconazole. These findings indicate that berberine exerts broad-spectrum antifungal effects through membrane disruption and CYP51 inhibition, highlighting its potential as a promising therapeutic option for fungal infections.

Dual Antimicrobial Activity of HTCC and Its Nanoparticles: A Synergistic Approach for Antibacterial and Antiviral Applications Through Combined In Silico and In Vitro Studies.

N-(2-hydroxyl) propyl-3-trimethyl ammonium chitosan chloride (HTCC), a quaternized chitosan derivative, has been shown to exhibit a broad spectrum of antimicrobial activity, especially against bacteria and enveloped viruses. Despite this, molecular docking studies showing its atomic-level mechanisms against these microorganisms are scarce. Here, for the first time, we employed molecular docking analyses to investigate the potential antibacterial activity of HTCC against Staphylococcus aureus and its antiviral activity against human immunodeficiency virus 1 (HIV-1). According to the findings, HTCC exhibited promising antibacterial activity with high binding affinities; however, it had limited antiviral activity. To validate these theoretical outcomes, experimental studies were conducted. Different derivatives of HTCC were synthesized and characterized using NMR, XRD, FTIR, and DLS. The in vitro assays validated the potent antibacterial efficacy of HTCC against S. aureus, whereas the antiviral studies did not show good antiviral activity. However, our research also revealed a promising avenue for further exploration of the antimicrobial activity of HTCC nanoparticles (NPs), since, thus far, no studies have been conducted to show the antiviral activity of HTCC NPs against HIV-1. The nanosized HTCC exhibited superior antiviral performance compared to the parent polymers, with complete (100%) inhibition of HIV-1 viral activity at the highest tested concentration (0.33 mg/mL).

Broad-spectrum antimicrobial activities of a food fermentate of Aspergillus oryzae.

The development of NP, a potent broad-spectrum antimicrobial, is a significant breakthrough in the ongoing challenge against microbial foodborne illnesses and the growing threat of antibiotic resistance. This food-grade culture broth of Aspergillus oryzae demonstrates exceptional broad-spectrum efficacy against a variety of harmful bacteria and fungi, including drug-resistant strains such as methicillin-resistant Staphylococcus aureus and prevalent food spoilage molds. NP exhibits strong bactericidal activity against various foodborne and ESKAPE pathogens, and strong antifungal activity against Penicillium species, Aspergillus fumigatus, and Candida albicans. The potent bactericidal and antifungal properties of NP are a result of its ability to disrupt microbial cell membranes leading to increased permeability. Furthermore, the genome-wide impact of NP on fungal gene expression and metabolic pathways underscores its comprehensive antimicrobial action, leading to transcriptomic and metabolic changes associated with cell death in A. fumigatus.

Synthesis, Characterization, and Biological Activity of New 4`-Functionalized Bis-Terpyridine Ruthenium(II) Complexes: Anti-inflammatory Activity Advances.

Ruthenium complexes incorporating 2,2':6',2''-terpyridine ligands have emerged as promising candidates due to their versatile biological activities including DNA-binding, anti-inflammatory, antimicrobial, and anticancer properties. In this study, three novel 4'-functionalized bis(terpyridine) ruthenium (II) complexes were synthesized. These complexes feature one ligand as 4-(2,2':6',2''-terpyridine-4'-yl) benzoic acid and the second ligand as either 4'-(2-thienyl)-2,2':6',2''-terpyridine, 4'-(3,4-dimethoxyphenyl)-2,2':6',2''-terpyridine, or 4'-(4-dimethylaminophenyl)-2,2':6',2''-terpyridine. Besides the chemical characterization by 1H and 13C NMR, mass spectrometry, and absorption and emission spectroscopy, the complexes were tested for their biological activity as anti-inflammatory, anticancer, and antimicrobial agents. Moreover, the toxicity of the Ru(II) complexes was assessed and benchmarked against diclofenac potassium and ibuprofen using a haemolysis assay. Biological evaluations demonstrate that these ruthenium complexes exhibit promising therapeutic potential with reduced haemolytic activity compared to standard drugs. They demonstrate substantial anti-inflammatory effects through inhibition of albumin denaturation along with moderate cytotoxicity against cancer cell lines and broad-spectrum antimicrobial activity. These findings highlight the multifaceted biomedical applications of 4'-functionalized bis(terpyridine) ruthenium (II) complexes, suggesting their potential for further development as effective and safe therapeutic agents.

Development of Low-Toxicity Antimicrobial Polycarbonates Bearing Lysine Residues.

Antibiotic resistance has been threatening public health for a long period, while the COVID pandemic aggravated the scenario. To combat antibiotic resistance strains, host defense peptides (HDPs) mimicking molecules have attracted considerable attention. Herein, we reported a series of polycarbonates bearing cationic lysine amino acid residues that could mimic the mechanism of action of HDPs and possess broad-spectrum antimicrobial activity. Moreover, those polymers had negligible toxicity toward red blood cells and mammalian cells. The membrane-disruption mechanism endows the lysine-containing polycarbonates with low possibility of resistance development and the fast killing kinetics, making them promising candidates for antimicrobial development.