Search Results (685)

Dermatophytes are highly infectious pathogenic fungi that colonize keratinized tissues like skin, hair, and nails, causing superficial infections such as tinea capitis, onychomycosis, tinea corporis, and tinea pedis in humans and animals. In immunocompromised patients, they may invade deeper tissues and organs, leading to severe or life-threatening conditions if untreated or inadequately managed. While most infections respond to topical antifungals, some require complex treatment and show resistance to standard therapies. Therefore, novel antifungal agents are needed. We investigated the antidermatophytic activity of imidazole-thiosemicarbazides against Microsporum canis, Trichophyton spp., and Chrysosporium spp. using the broth microdilution method, comparing results to ketoconazole and amphotericin B through minimal inhibitory concentration (MIC), half-maximal inhibitory concentration (IC₅₀), and selectivity index (SI). Iodine- and bromine-substituted compounds showed the strongest activity, with MICs of 15.15 (IC₅₀ < 1 μM; SI > 213) and 73.46 μg/mL (IC₅₀ < 1 μM; SI > 846) against T. tonsurans, and 3.87 (IC₅₀ = 7.21 μM; SI > 29.6) and 7.38 μg/mL (IC₅₀ = 11.06 μM; SI = 76.6) against M. canis. In silico analysis revealed interactions with α-keratin and lanosterol-14-α demethylase (the azole target enzyme), suggesting enhanced drug retention and action. These findings support these compounds as promising leads for further antifungal development. Full article

This study presents a green, single-step method for synthesizing nanocomposites based on reduced graphene oxide (RGO) and gold nanoparticles (AuNPs), using sodium citrate as a mild reducing and stabilizing agent. AuNPs were generated from chloroauric acid (HAuCl₄) directly on the surface of graphene oxide (GO), which was simultaneously reduced to RGO. Structural characterization via Transmission Electron Microscopy (TEM), High Resolution TEM (HRTEM) and Selected Area Electron Diffraction (SAED) confirms spherical AuNPs (10–60 nm) distributed on RGO sheets, with indications of nanoparticle aggregation. Dynamic Light Scattering (DLS) and zeta potential analysis support these findings, suggesting colloidal instability with higher RGO content. Biological evaluation demonstrates dose-dependent cytotoxicity in HaCaT keratinocytes, with IC₅₀ values (half maximal inhibitory concentration) decreasing as RGO content is increased. At moderate dilutions (1–25 µL/100 µL), the composites show acceptable cell viability (>70%). Antibacterial assays reveal strong synergistic effects against Escherichia coli, Staphylococcus aureus, and Bacillus subtilis, with sample RGO/Au 0.500/0.175 g/L showing complete E. coli inhibition at low Au content (0.175 g/L). The composite retained activity even in protein-rich media, suggesting potential for antimicrobial applications. These findings highlight the potential of RGO/AuNPs composites as multifunctional materials for biomedical uses, particularly in antimicrobial coatings and targeted therapeutic strategies. Full article

Polypore mushrooms have been widely recognized for centuries for their use in food and medicine due to their strong capacity to produce numerous biomolecules with beneficial effects on human health. Fomes fomentarius is one such species that remains poorly explored, particularly when growing in Morocco. Herein, this study aimed to characterize the bioactive compounds of F. fomentarius and evaluate its pharmacological properties. Spectrophotometric analysis showed that F. fomentarius revealed high levels of total phenolics (75.83 mg GAE/g dme) and flavonoids (37.62 mg CE/g dme). Gas chromatography–mass spectrometry (GC–MS) analysis identified 109 volatile and non-volatile compounds, primarily sugars (24), fatty acids (23), alcohols (10), organic acids (9), and terpenoids (6). In addition, liquid chromatography-mass spectrometry (LC-MS) analysis allowed the identification of 24 phenolic compounds, with isorhamnetin (2734.00 µg/g), p-hydroxybenzoic acid (409.00 µg/g), and kaempferol (351.10 µg/g) as the most abundant. Regarding pharmacological properties, F. fomentarius extract demonstrated strong antioxidant activity, with the DPPH radical-scavenging assay showing the highest potency, followed by β-carotene bleaching inhibition and ferric ion-reducing power, with EC₅₀ (half maximal effective concentration) values of 114.40, 174.50, and 250.70 µg/mL, respectively. Additionally, it exhibited broad-spectrum antimicrobial activity against all seven human pathogenic microorganisms, with Epidermophyton floccosum being the most susceptible ((minimum inhibitory concentration (MIC)) = 2 mg/mL and minimal fungicidal concentration (MFC) = 4 mg/mL) and A. fumigatus the most resistant (MIC = 26.67 mg/mL and MFC ≥ 64 mg/mL). Overall, the result indicated that Moroccan F. fomentarius is a rich source of diverse bioactive compounds with potent antioxidant and antimicrobial activities, supporting its potential for various applications. Full article

Background: Ephedra przewalskii Stapf stems are a traditional Mongolian medicine commonly used to treat infectious diseases. Previous in vitro experiments have shown that the extract powder derived from its stems possesses antiviral activity. However, the active compounds responsible for this activity in E. przewalskii Stapf have not yet been identified or evaluated. This study aimed to identify the active components in E. przewalskii that exhibit antiviral effects against SARS-CoV-2 in vitro and validate their antiviral activity. Methods: E. przewalskii stem extracts were subjected to high-performance liquid chromatography with varying methanol ratios in the mobile phase to obtain fractions with different polarities. Antiviral activity was assessed by infecting VeroE6/TMPRSS2 cells with the SARS-CoV-2 Delta strain and treating them with the obtained fractions. Infectious titers were measured using the 50% tissue culture infective dose (TCID₅₀) method, and half-maximal inhibitory concentration (IC₅₀) values were calculated for each fraction. The active components in the two fractions with the highest antiviral activity were identified and structurally characterized by nuclear magnetic resonance analysis. The antiviral activity of these compounds was confirmed by adding them to SARS-CoV-2-infected cells and measuring their infectious titers using the TCID₅₀ method. The IC₅₀ values were also calculated. Viral-particle inactivation assays were conducted by mixing the extracts with SARS-CoV-2 and measuring infectious titers. Results: (−)-Catechin, (+)-epigallocatechin-(2α→O→7,4α→8)-(−)-epicatechin, and ent-epicatechin-(4α→8;2α→O→7)-catechin were isolated from E. przewalskii. These compounds exhibited significant antiviral activity against SARS-CoV-2 but demonstrated minimal direct virucidal effects. Conclusion: (−)-Catechin, (+)-epigallocatechin-(2α→O→7,4α→8)-(−)-epicatechin, and ent-epicatechin-(4α→8;2α→O→7)-catechin exhibit antiviral activity against SARS-CoV-2 in infected cells. Full article

Nucleoside analogues are used as drugs and as labels in laboratory-based research. However, the effect of different nucleoside analogue mechanism(s) on cell sensitivity or mutagenesis is unclear. This is particularly important in cancer treatments where checkpoint proteins and DNA damage factors are often mutated. We tested six nucleoside analogues in fission yeast, Schizosaccharomyces pombe. We found that the mutations in the DNA replication checkpoint cause unique sensitivity profiles towards chemotherapeutic nucleoside analogues (gemcitabine, 5-fluorouracil, cytarabine) and the non-clinical analogue bromodeoxyuridine. Antiretroviral compounds, zidovudine and lamivudine, did not alter cell growth. We compared half-maximal inhibitory concentration (IC50) doses between checkpoint deficient yeast strains, examining culture growth and DNA mis-segregation. Intriguingly, gemcitabine and bromodeoxyuridine doses above the IC50 promoted better growth. Above each compound’s IC50 dose we saw that cells were insensitive to nucleoside analogue re-exposure, particularly in DNA replication checkpoint mutants (cds1∆, rad3∆). Thus, pairing nucleoside analogue use with personal genomics may inform drug choice, dose, and schedule. Finally, these data indicate that resistance may be predictable, informing clinical strategy. Full article

ECIS-based impedance biosensors have been extensively studied in various fields including cancer research, microbiology, and immunology. However, most studies have primarily focused on monitoring cellular behavior through impedance changes, with relatively less emphasis on interpreting the biological significance of impedance signals. In this study, we employed a multi-well array impedance biosensor to conduct IC₅₀ (half-maximal inhibitory concentration) analysis, a widely used metric for evaluating drug efficacy and toxicity in biological and pharmacological research. Specifically, we assessed the IC₅₀ values of puromycin, an aminonucleoside antibiotic known to inhibit protein synthesis. NIH/3T3 fibroblasts were exposed to various concentrations of puromycin, and real-time impedance monitoring was performed. Cell viability was assessed, and the IC₅₀ value of puromycin for NIH/3T3 cells was determined to be 3.96 µM using capacitance-based impedance analysis. Our findings demonstrate that the multi-well array impedance biosensor provides a rapid and quantitative method for drug toxicity evaluation, offering a valuable platform for drug screening and biocompatibility assessment. Full article

Cylindrospermopsis raciborskii is a toxin-producing cyanobacterium that is easy to overlook. It has strong environmental adaptability and is currently spreading around the world and gradually dominating to form a persistent bloom, causing ecological and environmental risks and drinking water safety issues. In this study, we systematically investigated the inhibitory effects of oleic acid on C. raciborskii and elucidated the underlying mechanisms through morphological observation, physiological assays, and bioinformatics analysis. Our results demonstrated that oleic acid strongly inhibits the growth of C. raciborskii, with a 72 h half-maximal effective concentration (EC₅₀) of 0.903 mg·L⁻¹. At 1.6 mg·L⁻¹, oleic acid achieved an inhibition rate of 99.5% within 48 h, indicating rapid suppression of cyanobacterial growth. Physiological analyses revealed that oleic acid severely impaired photosynthetic activity, as evidenced by significant reductions in key parameters (rETRmax, α, Fv/Fm, and Fv/Fo) and altered photosynthetic pigment composition, suggesting structural and functional damage to the photosynthetic apparatus. Morphological observations further showed that oleic acid disrupted filament integrity, inducing cell shrinkage, cytoplasmic vacuolation, cell wall detachment, membrane rupture, and eventual cellular disintegration. Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis indicated that oleic acid interferes with multiple metabolic processes, including nutrient and cofactor synthesis, membrane transport, and signal transduction, ultimately triggering algal cell death. This study highlights oleic acid as a promising eco-friendly agent for mitigating C. raciborskii blooms, offering potential applications in ecological prevention and emergency bloom control. Full article

Monoacylglycerol lipase (MAGL) degrades the endocannabinoid 2-arachidonyl glycerol. MAGL inhibitors, such as the triterpene pristimerin, alleviate neuropathic pain in animal models. In silico studies were carried out using SwissDock, PyRx-0.8 and CB-Dock2, to check if they correlated with the in vitro MAGL inhibition potency of various triterpenes. In terms of affinity, free energy of binding and docking scores to MAGL, pristimerin (52.75, −9.32, −10.83, and −11.5 kcal/mol) was better than euphol (44.86, −8.49, −9.56, and −10.7 kcal/mol), which in turn was better than β-amyrin (35.17, −7.37, −8.21, and −8.8 kcal/mol). Finally, β-amyrin was better than or equal to α-amyrin (35.10, −7.19, −7.95, and −8.6 kcal/mol). In molecular dynamic simulations (MDSs), pristimerin exhibited the highest stability and reached the steady state after 20 ns with the lowest root mean square fluctuation (RMSF) at the binding site, compared to the triterpenes. The reported half maximal inhibitory concentration (IC₅₀) values of recombinant human and rat MAGL inhibition were in the following order: α-amyrin > β-amyrin > euphol > pristimerin. Linear regression analysis showed that the affinity, free energy of binding, and docking scores significantly correlated with the IC₅₀ of MAGL inhibition. Amongst the triterpenes studied, pristimerin was the most potent inhibitor of MAGL and also had the highest affinity in the in silico studies. Thus, molecular docking and MDS results correlated with the potency of triterpenes inhibiting MAGL activity in vitro and could be used for screening of triterpenes prior to experimental validation. Full article

Ibuprofen (IBP), one of the most consumed drugs in the world, is only partially removed in Wastewater Treatment Plants (WWTPs). Its presence in effluents and sewage sludge introduces IBP into the environment. It is imperative to continue research on IBP degraders that can be used in the future to eliminate IBP at the WWTP level. This study describes the use of nine specific IBP-degrading bacteria isolated from sewage sludge (Achromobacter denitrificans, Bordetella petrii, Brucella tritici, Curtobacterium flaccumfaciens, Microbacterium paraoxydans, Pseudomonas citronellolis, Pseudomonas nitroreducens, Shinella zoogloeoides, Stenotrophomonas acidaminiphila) for the removal of IBP from water. Their half-maximal inhibitory concentration of IBP for bacterial growth (IC₅₀) revealed a high level of IBP tolerance. Degradation of IBP (10 mg L⁻¹) was effective for all the strains using glucose as a secondary substrate. Seven of the nine strains were shown to be IBP degraders for the first time by our research group, highlighting A. denitrificans CSW15, with almost 47% IBP degraded, and C. flacumfaciens CSW18, with 32.2% after 28 days. Three IBP transformation products were identified: 1-hydroxyibuprofen (1-OH-IBP), 2-hydroxyibuprofen (2-OH-IBP), and carboxyibuprofen (CBX-IBP). A comparison of the effectiveness of IBP degradation by the nine isolates with most other IBP-degrading bacteria previously reported was carried out. Full article

Helicobacter pylori infection, a leading cause of gastric ulcers and gastric cancer, presents a major health challenge, exacerbated by rising antibiotic resistance. This study investigated the antibacterial potential of plant-derived compounds, isolated from different plant species, against H. pylori. Thus, a library of 153 natural compounds and derivatives, including monoterpene indole and bisindole alkaloids, obtained from the African medicinal plant Tabernaemontana elegans was screened in vitro for minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) against H. pylori. Active compounds (1–7) were tested for anti-biofilm activity and cytotoxicity on VERO cells to determine their half-maximal cytotoxic concentrations (CC₅₀). Six monoterpene indole alkaloid azine derivatives (1–6) and vobasinyl-iboga type bisindole alkaloid (7) displayed antibacterial activity, with MICs between 10 and 20 µM. Compounds 2, 3, and 6 exhibited bactericidal activity, with MBCs of 20 µM. Notably, compounds 1 to 4 inhibited H. pylori biofilm formation at sub-inhibitory concentrations. Cytotoxicity assays revealed CC₅₀ values above MICs, indicating a favorable safety profile for potential therapeutic use. This study highlights the potential of T. elegans monoterpene indole alkaloids as antibacterial agents and supports further exploration of plant-derived compounds as alternative treatments for H. pylori, offering a promising approach to address antibiotic resistance in gastrointestinal diseases. Full article

Root rot is one of the most serious diseases affecting Astragalus membranaceus, significantly reducing its yield and quality. This study focused on root rot in Astragalus membranaceus var. mongholicus. Pathogenic fungi were isolated and identified. The pathogenicity of seven strains of pathogenic fungi was verified according to Koch’s postulates. The inhibitory effects of eight classic fungicides and nine strains of biocontrol agents on the pathogenic fungi were determined using the mycelial growth rate method. Through morphological and ITS phylogenetic analyses, strains CDF5, CDF6, and CDF7 were identified as Fusarium oxysporum, while strains CDF1, CDF2, CDF3, and CDF4 were identified as Fusarium solani. Indoor virulence tests showed that, among the eight tested fungicides, carbendazim exhibited the strongest inhibitory effect on the mycelial growth of both F. oxysporum and F. solani, with a half-maximal effective concentration (EC₅₀) value of (0.44 ± 0.24) mg/mL, making it a highly promising chemical agent for the control of A. membranaceus var. mongholicus root rot. Among the nine biocontrol agents, KRS006 showed the best inhibitory effect against the seven pathogenic strains, with an inhibition rate ranging from 42.57% to 55.51%, and it can be considered a candidate strain for biological control. This study identified the biocontrol strain KRS006 and the chemical fungicide carbendazim as promising core agents for the biological and chemical control of A. membranaceus var. mongholicus root rot, respectively, providing a theoretical foundation for establishing a dual biocontrol–chemical control strategy. Based on the excellent performance of the biocontrol bacteria and fungicides in the pathogen control tests, future research should focus on field trials to verify the synergistic effect of this integrated control strategy and clarify the interaction mechanism between the antibacterial metabolites produced by the biocontrol bacteria KRS006 and carbendazim. Additionally, continuous monitoring of the evolution of Fusarium spp. resistance to carbendazim is critical to ensure the long-term sustainability of the integrated control system. Full article

Objectives: The aim of this work was to determine the phenolic composition of sweet wormwood (Artemisia annua L., Asteraceae) from controlled cultivation in Serbia and to assess the potential antioxidant effects and cytotoxicity. Methods: High-performance liquid chromatography was used to determine the phenolic composition of Artemisia annua ethanolic extract. The antioxidant activity was studied using in vitro tests of inhibition of the neutralization of 2,2-diphenyl-1-picrylhydrazyl (DPPH), hydroxyl (OH), and nitroso (NO) radicals, as well as the process of inhibiting lipid peroxidation and the ferric reducing antioxidant power (FRAP). The cytotoxicity was evaluated by the effect on three cell lines (the rat pancreatic insulinoma cell line (Rin-5F), the rat hepatoma cell line (H4IIE), and human hepatocellular carcinoma (Hep G2)) using the MTT test of viability. Results: Ethanol extract showed the highest potency in inhibiting the DPPH radical, and the half maximal inhibitory concentration (IC₅₀) was 5.17 μg/mL. Chlorogenic acid was the dominant phenolic compound with an amount of 651 μg/g of dry extract. The results of the MTT viability test showed that the extract has the potential to inhibit the growth of the Rin-5F and Hep G2 cell lines, while no growth inhibition was observed on the H4IIE cell line. Conclusions: Undoubtedly, Artemisia annua is a powerful plant and a rich source of phenolic compounds. Inhibitory activity on causes of oxidative stress shows that the plant has a good antioxidant effect. Also, the anticancer activity shown through the inhibition of cell growth is not negligible. Full article

The optimization of bioactive compound mixtures is critical for enhancing pharmacological efficacy. This study investigates, for the first time, the combined effects of eugenol, camphor, and terpineol, focusing on their half-maximal inhibitory concentrations (IC₅₀) across multiple biological responses related to diabetes management. Using a mixture design approach, the objective was to determine the optimal formulation that maximizes bioactivity and validate the findings experimentally. A simplex-centroid design was applied to evaluate the combined effects of eugenol, camphor, and terpineol on AAI _IC50, AGI _IC50, LIP _IC50, and ALR _IC50 responses. The desirability function was used to determine the ideal composition. The optimized formulation was experimentally validated using in vitro assays, and IC50 values were measured for each response using standard protocols. Results: The optimal formulation identified was 44% eugenol, 0.19% camphor, and 37% terpineol, yielding IC₅₀ values of 10.38 µg/mL (AAI), 62.22 µg/mL (AGI), 3.42 µg/mL (LIP), and 49.58 µg/mL (ALR). The desirability score (0.99) confirmed the effectiveness of the optimized blend. Experimental validation of the optimal mixture resulted in IC₅₀ values of 11.02 µg/mL (AAI), 60.85 µg/mL (AGI), 3.75 µg/mL (LIP), and 50.12 µg/mL (ALR), showing less than 10% deviation from predicted values, indicating high model accuracy. This study confirms the combined potential of eugenol, camphor, and terpineol, with eugenol and terpineol significantly enhancing bioactivity. The validated formulation demonstrates potential for pharmaceutical and cosmeceutical applications. Future research should explore mechanistic interactions, bioavailability, and in vivo efficacy to support the development of optimized natural compound-based therapies. Full article

Background/Objectives: Currently there are very few effective oral antileishmanial treatments. In this study we evaluated a new bis(pyridine-2-carboxamidine) antileishmanial drug (JNII40_base) and its hydrochloride salt (JNII40_HCl). Methods: The characterization studies performed allowed us to determine the crystallinity, hydration water, and presence of hydrogen bonds in these drugs. Different dissolution methods were employed to predict intestinal absorption. A high-performance liquid chromatography–mass spectrophotometry (HPLC-MS/MS) method was developed for the determination of JNII40 in plasma. Results: Pharmacokinetic studies in rats of JNII40_base at 100 and 20 mg/kg, and JNII40_HCl at 20 mg/kg, showed a non-linear pharmacokinetic at high doses. An innovative biorelevant medium of phosphate buffer pH 6.8 with polysorbate 80 at 0.6% (w/v) showed high concentration values for JNII40_base at 30 min, which predicts good intestinal absorption. These results were consistent with the bioavailability data, which exhibited a significant (p < 0.05) increase in maximum plasma concentration (C_max) and a slight delay in time to maximum (T_max) compared to JNII40_HCl. Furthermore, the sustained release of JNII40_base in this biorelevant media was related to high plasma concentration values at 24 h (C_24h) observed in bioavailability studies. These plasma concentrations of JNII40_base were above the half-maximal inhibitory concentration (IC₅₀) against promastigote and amastigote forms of Leishmania donovani, which is indicative of effectiveness and should reduce the occurrence of drug resistance during treatments. Conclusions: The bioavailability and pharmacokinetic data support the consideration of this drug for further in vivo studies as an oral antileishmanial treatment. Full article

Background: Antibiotic-resistant bacteria, especially Staphylococcus species, are a growing concern in healthcare settings and infections caused by multidrug-resistant strains are difficult to treat. Therefore, it is imperative to explore new treatment methods for these infections such as combinations of natural compounds with antibiotics. Methods: The main objective of this study was to investigate the antimicrobial activity of caffeic acid against staphylococcal strains. The viability of bacterial cells and half maximal inhibitory concentration (IC₅₀) for caffeic acid were also examined. The minimum inhibitory concentration (MIC) of the caffeic acid was determined using a serial microdilution method. To study the combined effect of caffeic acid and erythromycin, the fractional inhibitory concentrations (FICs) were determined. Results: Caffeic acid inhibited the growth of all the tested isolates, with MIC values ranging from 256 to 1024 µg/mL and reduced bacterial cell viability at concentrations corresponding to MIC values. Caffeic acid and erythromycin showed a synergistic effect when used together against three examined strains and had an additive effect against two isolates. However, their combination was indifferent against the seven remaining staphylococci tested. Conclusions: The results of our research demonstrate that caffeic acid has antimicrobial properties against the tested strains. Full article