Search Results (1,346)

Background/Objectives: The bacterial cell division machinery is emerging as an attractive target for antimicrobial compounds. FtsZ, a highly conserved essential division protein, is the target for a number of small molecules such as benzamides. Recent studies show that benzodioxane-benzamides (BDOBs) are among the most potent inhibitors of FtsZ function in Gram-positive bacteria, although their ability to inhibit Gram-negative FtsZ, in particular Escherichia coli FtsZ, has been more controversial. Methods: Here, we use genetic and cytological methods to demonstrate that FtsZ of efflux pump-disabled E. coli can be efficiently targeted by BDOBs. Results: We show that engineered mutants and spontaneous variants map in or near the interdomain cleft (IDC) of FtsZ that confers resistance to BDOBs, similar to previous results with Gram-positive FtsZs. We also uncover spontaneous extragenic mutants that can confer high levels of resistance to at least one potent BDOB, including a mutant that encodes a novel hyperfission variant of the essential cell division protein FtsW. Conclusions: Our evidence indicates that as with Gram-positive bacteria, the IDC of Gram-negative bacterial FtsZ is directly targeted by BDOBs, provided efflux pumps are disabled. We also conclude that FtsZ-independent factors can influence the effect of BDOBs on E. coli cell division, including activation of division septum synthesis. Full article

Background/Objectives: Epilepsy is characterized by unpredictable seizures and drug resistance, along with rising antimicrobial resistance (AMR), highlighting the urgent need for innovative dual-action therapies. This study aimed to design, develop, and evaluate novel pyrazolone derivatives for a dual antimicrobial and antiepileptic potential. Methods: Novel pyrazolone derivatives were designed, synthesized (using 2,4-dinitrophenylhydrazine/semicarbazide condensation with ethyl acetoacetate), and evaluated through molecular docking against antimicrobial (4URM, 3FYV, 3FRA) and neuronal targets (4COF, 5TP9, 5L1F). The in vitro antimicrobial activity was assessed against Gram-positive (S. aureus) and in vitro Gram-negative (E. coli, P. aeruginosa) strains via agar cup plate assays, while in vivo antiepileptic efficacy was tested in a PTZ-induced seizure model in Swiss albino mice. Results: Compound IIa showed potent dual activity, inhibiting E. coli (9 mm zone at 80 μg/mL) and S. aureus (9.5 mm at 80 μg/mL), alongside a significantly delayed seizure onset in the PTZ-induced mouse model (100% survival rate, 45 sec delayed seizure onset, p < 0.001). Compounds Ia and Id showed selective activity against E. coli (6 mm at 80 μg/mL) and P. aeruginosa (7 mm at 80 μg/mL), respectively. Docking studies revealed that compound IIa has a superior binding affinity (−7.57 kcal/mol for 3FYV) compared to standards, driven by hydrogen bonds (SER X: 49) and hydrophobic interactions (LEU X: 20). Conclusions: This study presents a novel approach by proposing a rationally designed pyrazolone scaffold exhibiting both antimicrobial and antiepileptic activity, which integrates in silico modeling with experimental validation. Compound IIa emerged with preliminary dual biological activities, exhibiting strong antibacterial activity, a superior binding affinity toward both bacterial and neuronal targets, and notable seizure prevention in vivo. These findings show the potential of multifunctional pyrazolone derivatives as a new treatment strategy for addressing drug-resistant infections linked to epilepsy and support further optimization toward clinical development. Full article

Background/Objectives: The genus Tristerix comprises at least ten species, found from southern Chile to Colombia in South America. In Chile, several species of these hemiparasitic plants are known as quitral or quintral. Quitral, mainly T. corymbosus (syn. T. tetrandus), is used in alternative medicine for its anti-inflammatory, digestive, hemostatic, hypocholesterolemic, and wound-healing properties. This study investigates the phytochemical composition and antimicrobial properties of T. corymbosus. Methods: A hydroalcoholic extract of T. corymbosus was prepared from leaves and small branches. The addition of methanol, on the extract, produced precipitation allowing us to isolate a methanol-soluble fraction, a brown powder obtained after filtration, and a tar-like residue remaining in the flask. These fractions were resuspended and tested for antimicrobial activity. Results: All fractions showed activity against Streptococcus pyogenes, but not E. coli. The brown powder exhibits the strongest potency against Gram-positive bacteria, some Gram-negative and C. albicans. HPLC-MS analysis revealed presence of lipidic compounds with surfactant properties. Conclusions: The abundant lipidic molecules present in the analyzed fraction likely account for the antimicrobial effects through affecting membrane structure of microorganisms supporting the traditional wound-healing uses of T. corymbosus in ancestral medicine. Full article

Background/Objectives: The rise in antimicrobial resistance is one of the major challenges to global health systems, which necessitates the development of new antibacterial compounds. The bioactive compounds of brown seaweed Sargassum duplicatum have demonstrated potential antibacterial activity. This study applied metabolomic profiling and molecular networking in combination with antibacterial screening assays to assess the antimicrobial properties of S. duplicatum extracts against multidrug-resistant bacteria. Methods: Two extraction methods, i.e., maceration and microwave extraction, were used. Therewith, untargeted metabolomic profiling was performed using Liquid Chromatography–High Resolution Mass Spectrometry (LC-HRMS). Molecular networks (MNs) were established and compound dereplication was conducted using the spectral database of the Global Natural Products Social Molecular Networking platform (GNPS). Additionally, antimicrobial assays were conducted against Gram-positive and Gram-negative bacterial strains, including multidrug-resistant bacteria, i.e., methicillin-resistant Staphyloccocus aureus ATCC 33592 (MRSA) and β-lactamase, producing Escherichia coli ATCC 35218 (TEM-1 positive strain). Result: Dereplication resulted in the prediction of six compounds with reported antimicrobial properties, i.e., 13-docosenamide, 9-octadecenamide, pheophorbide A, ouabain, sarmentoside B and AC1L1X1Z. Antibacterial screening of the extracts revealed that the ethyl acetate maceration extracts exhibited the strongest inhibitory activity, with inhibition values between 85 and 98% against S. aureus ATCC 33592. Conclusions: This metabolomics study requires further research to isolate, purify, confirm, and validate the dereplicated compounds that may have potential antibacterial activity. Full article

Background/Objectives: The global rise in multidrug-resistant (MDR) bacteria, particularly methicillin-resistant and methicillin-susceptible Staphylococcus aureus (MRSA and MSSA), continues to pose a major public health challenge, including in Hawaii. This underscores the need to discover new antimicrobial agents from natural sources. Guided by teachings from a Buddhist master regarding the medicinal value of lichens, we investigated the endemic Hawaiian lichen Cladonia skottsbergii. Methods: Specimens of C. skottsbergii were collected from the Lotus Buddhist Monastery in Mountain View, Hawaii. A methanolic extract was prepared and purified using chromatographic techniques, and compound structures were elucidated through spectroscopic analyses and single-crystal X-ray diffraction. The antibacterial activity of the compounds was assessed against Gram-positive strains (MRSA, MSSA) and Gram-negative bacteria (Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa). Cytotoxicity was assessed using A549 (non-small cell lung cancer) and Vero E6 (non-tumorigenic) cell lines. Results: Three compounds were isolated: clarosione (1), a newly identified trichlorinated xanthone, and two known metabolites, (S)-usnic acid (2) and perlatolic acid (3). Compounds 2 and 3 demonstrated strong inhibitory effects against MRSA and MSSA. Their minimum inhibitory concentrations (MICs) ranged from 2 to 4 µg/mL, compared with vancomycin (0.5–1 µg/mL). Cytotoxicity testing showed higher sensitivity in A549 cells than in Vero E6 cells, resulting in favorable selectivity indices for the active compounds. Conclusions: In the current study, a new compound, clarosione (1) was discovered. This enhances our understanding of the constituents of C. skottsbergii and its potential antibacterial properties. Lichen-derived compounds may serve as lead candidates for further development, and further study is warranted. Full article

Antimicrobial resistance (AMR) is a major global health concern, which complicates treatment of microbial infections and wounds. Conventional therapies are no longer effective against drug resistant microbes; hence, novel antimicrobial approaches are urgently required. Silver nanoparticles (AgNPs) offer stronger antimicrobial activity, and in situ synthesis improves stability, uniformity, cost efficiency, and bioactivity while minimising contamination. These features make AgNPs well-suited for incorporation into textiles and wound dressings. Red wine extract (RW-E), rich in antioxidant and anti-inflammatory compounds was used to hydrothermally synthesise RW-AgNPs and RW-AgNPs-loaded on cotton (RWALC) by optimising pH and RW-E concentration. Characterisation was performed using UV–Vis spectroscopy, dynamic light scattering (DLS), and High Resolution and Scanning electron microscopy (HR-TEM and SEM). Antibacterial activities were evaluated against human pathogens through agar disc diffusion assay for RWALC and microdilution assay for RW-AgNPs. RWALC showed higher potency against both Gram-negative and Gram-positive bacteria, with inhibition zones of 12.33 ± 1.15 to 23.5 ± 5.15 mm, that surpassed those of ciprofloxacin (10 ± 3 to 19.17 ± 1.39 mm at 10 μg/mL). RW-AgNPs exhibited low minimum inhibitory concentrations (MIC: 0.195–3.125 μg/mL) and minimum bactericidal concentrations (MBC: 0.78–6.25 μg/mL). Preincubation with β-mercaptoethanol (β-ME) inhibited the antibacterial activity of RWALC, suggesting that thiolated molecules are involved in AgNPs-mediated effects. This study demonstrated that green-synthesised RW-AgNPs, incorporated in situ into cotton, conferred strong antibacterial properties, warranting further investigation into their mechanisms of action. Full article

The diterpene sessein, isolated from Salvia sessei, is a metabolite of interest due to its conjugated p-quinone system, δ-lactone ring, and phenolic hydroxyl in C-12. These functionalities make it an ideal starting point for reactivity studies and semi-synthetic derivatization. In this work, we report the obtainment of two derivatives by selective esterification of phenolic hydroxyl in C-12, through acetylation and benzoylation reactions under mild conditions and with high yields. The structures were characterized by UPLC-MS, FTIR, and NMR spectroscopy ¹H, ¹³C, and 2D, which allowed to precisely confirm the modifications made in the derivatives. These results confirm that hydroxyl in C-12 constitutes a privileged site of reactivity within the royleanone family, consolidating sessein as a versatile nucleus for the generation of derivatives. Finally, the preliminary evaluation of the antimicrobial activity showed that sessein shows a broad spectrum of action against Gram-positive, Gram-negative, and Candida albicans strains. The acetylated derivative showed an increase in activity against gram-negative bacteria, while the benzoyl derivative had a loss of effect at the concentrations evaluated. These findings demonstrate that structural modifications influence the properties of the derivatives with respect to the compound sessein. Full article

Seven amidrazones containing a characteristic NH₂–N=C(Ar¹)–NHAr² moiety, where Ar¹, Ar² are phenyl, 4-methylphenyl, 4-nitrophenyl, 2-pyridyl, and 4-pyridyl substituents, denoted as 2a–2g, were synthesized by the reactions between thioamides and hydrazine. Their molecular structures were confirmed by ¹H, ¹³C, ¹H-¹³C HMQC, ¹H-¹³C HMBC, and ¹H-¹⁵N HMBC NMR spectroscopy, with complete assignment of the detected signals, as well as by high-resolution mass spectra. The biological activity of all compounds was studied, exhibiting antioxidant properties determined by 2,2-diphenyl-1-picrylhydrazyl (DPPH) and ferric reducing antioxidant power (FRAP) methods, inhibitory potential against digestive tract enzymes (α-amylase, lipase, pepsin), cytotoxicity (hemolysis), and antimicrobial activities (against Gram-positive and Gram-negative bacteria, and a fungus). The antioxidant activity of the studied amidrazones varied from 83.34% to 93.27% and 1.01–5.79 mM FeSO₄ for the DPPH and FRAP methods, respectively. Moreover, these derivatives revealed inhibition potential against α-amylase (28.6–86.8%), lipase (28.0–60.0%), and pepsin (34.1–76.6%), which increased when increasing their concentrations from 0.2 to 1 mg/mL. Among them, compound 2d (possessing 2-pyridyl and 4-nitrophenyl substituents) stood out in particular, as a potent antioxidant (DPPH = 90.43%, FRAP = 4.73 Mm FeSO₄) with the highest activity against Gram-positive bacteria: S. aureus (MIC = 64 μg/mL), G. rubripertincta (MIC = 64 μg/mL), and fungus: C. albicans (MIC = 32 μg/mL); high α-amylase (86.8%) inhibition at the highest concentration (1 mg/mL); and lipase (38.0%) and pepsin (43.8%) inhibition at the lowest concentration (0.2 mg/mL). The obtained results were analyzed by unsupervised multivariate techniques to confirm significant differences in the biological activity of amidrazones depending on the Ar¹ and Ar² substituents. Full article

The anti-inflammatory scaffold 5-aminosalicylic acid, which is widely used in therapeutic applications, was chosen for the synthesis of N-[3-(hydrazinecarbonyl)-4-hydroxyphenyl]acetamide (1) to enhance its antibacterial properties. The condensation of hydrazide 1 with aromatic aldehydes provided hydrazone derivatives 2a–f, whereas cyclocondensation reactions and other related transformations afforded five-membered heterocycles, including pyrrole 3, pyrazole 4, pyrrolidinone 7, oxadiazoles 9, 10, thiadiazole 14, and triazole 15. Additional modifications yielded acetylhydrazine derivative 11, which was O-alkylated to analogue 12. Antibacterial evaluation showed stronger activity against Gram-positive bacteria such as S. aureus and MRSA than against Gram-negative strains of E. coli and S. Enteritidis, consistent with differences in cell membrane permeability. Notably, derivatives containing pyrrolidinone 7, thiosemicarbazide 13, and 1,3,4-thiadiazole 14 exhibited potent bactericidal activity against S. aureus and MRSA, while hydrazones 2b, 2c, 2f, pyrrole 3, and pyrrolidinone 7 exhibited activity against E. coli. These results provide a practical strategy for the discovery of heterocyclic compounds and emphasise the potential of functionalised 5-aminosalicylic acid derivatives as prime candidates for the development of broad-spectrum antibacterial agents. Full article

Background: Aggregatibacter actinomycetemcomitans is a Gram-negative, facultative anaerobic, immobile oral bacterium responsible for the secretion of virulence factors, namely leukotoxin (LtxA), a large exotoxin of the RTX family that enables the bacterium to evade the immune system by destroying leukocytes, resulting in aggressive periodontitis (AP) leading to tooth loss. Methods: This study aimed to screen 106 molecules derived from Moroccan propolis in order to identify potential inhibitors of the active sites of LtxA based on molecular docking, ADMET property evaluation, and molecular dynamics (MD) simulation. Results: Epigallocatechin gallate (EGCg), used as a reference compound, showed binding energies of −6.9 kcal/mol, −6.1 kcal/mol, −6.5 kcal/mol, and −5.9 kcal/mol with the four active sites P1, P2, P3, and P4, respectively. By establishing conventional hydrogen bonds, pi-alkyl bonds, and non-covalent pi–pi bonds. Chrysin and luteolin showed favorable binding affinities with the four active sites, named as follows: P1–P4 (P1–chrysin = −7.5 kcal/mol; P2–chrysin = −7.9 kcal/mol; P3–chrysin = −8.1 kcal/mol; P4–chrysin = −6.9 kcal/mol; P1–luteolin = −7.3 kcal/mol; P2–luteolin = −7.6 kcal/mol; P3–luteolin = −8.1 kcal/mol; P4–luteolin = −7.3 kcal/mol). The binding affinity of these two propolis derivatives was stabilized by pi−sigma bonds, pi−alkyl bonds, conventional hydrogen bonds, pi-cation interactions, non-covalent pi–pi bonds, and carbon–hydrogen bonds. According to free energy calculations performed with Prime MM-GBSA, the complexes formed by chrysin demonstrated the most stable interactions due to Van der Waals and lipophilic forces. Luteolin formed significant interactions, but slightly weaker than those of chrysin. These results reveal the inhibitory potential of chrysin and luteolin with protein active sites. MD simulations corroborated the excellent stability of complexes formed by chrysin, as indicated by low RMSD values, suggesting favorable dynamic behavior. Conclusions: These results highlight the potential of chrysin as a versatile inhibitor capable of interacting with the four active sites. These findings are a strong foundation for further experimental confirmations. Full article

Background/Objectives: Colistin (polymyxin E) has re-emerged as a last-hope treatment against MDR Gram-negative pathogens due to the development of extensively drug-resistant Gram-negative bacteria. Unfortunately, rapid global resistance towards colistin has emerged, which represents a major public health concern. In this context (CBD), a lipophilic molecule derived from Cannabis sativa, exhibits antimicrobial activity mainly against Gram-positive bacteria but is generally ineffective against Gram-negative species. However, synergistic antibacterial activity between CBD and polymyxin B has been reported. The objective of this work is to analyze the colistin–CBD synergy against clinically relevant Gram-negative isolates displaying diverse mechanisms of colistin resistance and to explore the basis of the possible mechanism of action involved in the first steps of this synergy. Methods: Microbiological assays, minimal inhibitory concentration, cell culture, synergy tests by checker board and time kill, biofilm inhibition evaluation by crystal violet and MTT, SEM (scanning electron microscopy), molecules interaction analysis by nuclear magnetic resonance (NMR). Results: The colistin–CBD combination displayed synergy in colistin resistant Gram-negative bacteria and also disrupted preformed biofilms and killed bacteria within them. Time-kill assays revealed rapid bactericidal activity and SEM showed mild surface alterations on bacterial outer membranes after sublethal colistin monotherapy. Furthermore, a series of sequential treatment assays on colistin-resistant Escherichia coli showed that simultaneous exposure to both compounds was required for activity, as introducing a washing step between treatments abolished the antibacterial effect. In order to obtain deeper insight into this mechanism, NMR analyses were performed, revealing specific molecular interactions between CBD and colistin molecules. Conclusions: These results provide evidence for the first time that both molecules engage through a specific and structurally meaningful interaction and only display synergy when acting together on colistin-resistant bacteria. Full article

Goldenrod (Solidago gigantea Aiton) is a highly invasive species in Europe (e.g., Poland, Germany, and the Czech Republic) whose secondary metabolites can serve as potential sources of bioactive compounds. This study evaluated the phytochemical profile of S. gigantea extracts and evaluated their antibacterial, insecticidal, and phytotoxic activities. The extracts were found to be rich in flavonoids (TFC = 101 mg QE/g) and phenolics (TPC = 175 mg GAE/g), with chlorogenic acid and rutin as dominant constituents. Strong antibacterial activity was observed against Gram-positive bacteria, particularly Staphylococcus spp. (MIC₉₀ = 2.3 mg/mL; MBC = 5 mg/mL), while Gram-negative bacteria were less sensitive, with moderate susceptibility in Rhizobium radiobacter and Pseudomonas syringae. The extract exhibited fungistatic activity against all tested filamentous fungi, with Fusarium species being the most sensitive (49–56% growth inhibition at 10 mg/mL). Insecticidal assays demonstrated significant mortality of Tribolium confusum adults at 2.5–7.0 mg/mL and feeding inhibition at concentrations as low as 0.5 mg/mL. Seedling growth tests showed dose-dependent effects—from mild suppression to moderate stimulation, varying by plant species. Foliar application revealed both stimulatory and inhibitory effects, with the strongest biomass reduction in cress at 10 mg/mL (−45%). These findings indicate that S. gigantea extracts possess potent antibacterial, antifungal, insecticidal, and allelopathic activities. Their concentration-dependent effects on pathogens and plants highlight potential applications in sustainable agriculture, including natural crop protection and integrated pest management. Full article

Background/Objectives: Essential oils are liquid natural volatile mixture of compounds with several bioactive properties, which make them useful in a wide range of pharmaceutical applications. The aim of this work is to explore the antimicrobial impact of Cymbopogon martini essential oil against human clinical bacterial isolates from the skin and respiratory tract while also assessing its impact on mammalian cells. Geraniol, its main component according to GC-MS analysis, was evaluated under the same conditions. Methods: The composition of the essential oil was provided by the supplier. To elucidate the antimicrobial activity, the minimum inhibitory concentration (MIC) and the minimum bactericidal concentration (MBC) were determined. The impact on mammalian hepatic cells was determined using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Results: The essential oil showed activity against Gram-positive bacteria from the Streptococcus and Staphylococcus genera, with MIC values ranging from 125 to 250 µg mL⁻¹ for Streptococcus agalactiae, Streptococcus anginosus, Streptococcus disgalactiae， and Streptococcus pyogenes. It also displayed activity against some of the tested Gram-negative bacteria, namely, Escherichia coli (MIC 350 µg mL⁻¹), Moraxella catarrhalis (MIC 250 µg mL⁻¹), and Morganella morganii (MIC 350 µg mL⁻¹). In most cases, the essential oil showed lower MIC values than geraniol. Additionally, palmarosa oil had a weaker impact than geraniol in HepG2 cells. Conclusions: Both the essential oil and the pure compound exhibited activity against clinical isolates obtained from skin and respiratory tract samples. Full article

Paeonia lactiflora Pall. is a perennial herbaceous plant widely renowned for its floral ornamental appeal, distinctive pleasant scent, and utilization in folk remedies. Roots and barks are traditionally used in Chinese medicine for various properties, including anti-inflammatory, antioxidant, antibacterial, anticancer, cardiovascular, and neuroprotective effects. Considering the growing interest and demand in the pharmaceutical and cosmetic fields for sustainable and bioactive botanical derivatives, this study aimed to apply NADES (natural deep eutectic solvents) extraction on fresh flowers of Paeonia lactiflora Pall. The purpose was to obtain a natural, multifunctional, and ready-to-use cosmetic ingredient with concurrent antioxidant activity, antimicrobial functionalities, and olfactive properties. The eutectic systems selected in this study were composed of betaine as the hydrogen bond acceptor and glycerol and/or sorbitol as the hydrogen bond donors. These eutectic systems under microwave activation led to a rapid extraction, from peony fresh flowers, of considerable phenolic amounts (from 33.0 to 34.4 mg of gallic acid equivalents per gram of fresh flowers), which confer to the whole NADES-based extract an excellent radical scavenging activity (around 87.5%, compared to Trolox) and a pleasant fragrance, due to the extraction of some characteristic volatile compounds, as confirmed by GC-MS analysis. Antimicrobial assays against different Gram-positive and Gram-negative strains demonstrated good inhibitory activity of the sample against multidrug-resistant Staphylococcus species (MIC ranging from 0.9 to 14.5 mg/mL) and against Enterococcus species (from 28.8 to 57.8 mg/mL). Furthermore, results on different Staphylococcus aureus strains disclosed additional interesting anti-biofilm properties. Preliminary long-term studies (up to 9 months) on these combined properties highlighted the stabilizing effect of NADESs on the active metabolites, confirming their potential as natural and functional ingredients that could be directly incorporated into pharmaceutical and cosmetic formulations, offering enhanced efficacy and improved stability. Full article

Photosynthetic prokaryotes known as cyanobacteria produce an extensive range of primary and secondary metabolites that serve multiple biotechnological and biomedical purposes. The non-model filamentous Phormidium species capture researchers’ attention through their biotechnological potentials from diverse metabolites and their ability to thrive in tough environments while producing bioactive compounds. In this study, a thermotolerant strain of Phormidium ambiguum was isolated from the Chundzha thermal springs in southeastern Kazakhstan and characterized morphologically, physiologically, and biochemically. This cyanobacterium demonstrated fast growth in its culture media along with significant accumulation of proteins (44.8% DM), carbohydrates (45% DM), and photosynthetic pigments like chlorophyll a and valuable carotenoids, including b-carotene, myxoxantophyll and zeaxanthin. The LC-ESI-MS/MS analysis of cyanobacterial non-polar extract identified 150 potential metabolites which include fatty acid derivatives, terpenoids and carotenoid-related compounds known for their antioxidant and antimicrobial properties, as well as immune system stimulation. Biological assays confirmed a weak antioxidant capacity in the DPPH test, while in immunological assays, the extract of P. ambiguum stimulated T lymphocyte proliferation and activation, as well as NK cell proliferation in vitro. It also exhibited moderate antibacterial activity towards tested Gram-negative and Gram-positive bacterial strains. While additional studies are required to address environmental robustness, biosynthetic regulation, and practical scalability, the present findings indicate that P. ambiguum represents a valuable non-model cyanobacterium for exploratory bioprospecting. Its metabolite profile and observed bioactivities support further investigation of this thermotolerant strain as a potential source of immunomodulatory, antioxidant, and antimicrobial compounds under controlled conditions. Full article