Search Results (857)

Cancer and infectious diseases are major causes of global morbidity and mortality stressing the need to find novel drugs with promising dual anticancer and antimicrobial efficacy. Gold complexes have been studied for the past years due to their anticancer properties, with a few of them displaying antimicrobial properties, which support their pharmacological interest. Within this scope, we investigated six gold bisdithiolate complexes [Au (bdt)₂]⁻ (1), [Au (dcbdt)₂]⁻ (2), [Au (3-cbdt)₂]⁻ (3), [Au (4-cbdt)₂]⁻ (4), [Au (pdt)₂]⁻ (5) and [Au (dcdmp)₂]⁻ (6), and) against the ovarian cancer cell lines A2780 and A2780cisR, the Gram-positive bacteria Staphylococcus aureus Newman, the Gram-negative bacteria Escherichia coli ATCC25922 and Burkholderia contaminans IST408, and the pathogenic yeasts Candida glabrata CBS138 and Candida albicans SC5134. Complexes 2 and 6, with ligands containing aromatic pyrazine or phenyl rings, substituted with two cyanonitrile groups, showed after 24 h of incubation high anticancer activities against A2780 ovarian cancer cells (IC₅₀~5 µM), being also able to overcome cisplatin resistance in A2780cisR cells. Both complexes induced the formation of ROS, activated caspase-3/7, and induced necrosis (LDH release) in a dose-dependent way, in a greater extent in the case of 6. Among the bacterial and fungal strains tested, only complex 6 presented antimicrobial activity against S. aureus Newman, indicating that this complex is a potential novel anticancer and antibacterial agent. These results delve into the structure-activity relationship of the complexes, considering molecular alterations such as replacing a phenyl group for a pyrazine group, and the inclusion of one or two cyanonitrile appendage groups, and their effects on biological activity. Overall, both complexes were found to be promising leads for the development of future anticancer drugs against low sensitive or cisplatin resistant tumors. Full article

Palindromic antimicrobial peptides (PAMs) constitute versatile scaffolds for the design and optimization of anticancer agents with applications in therapy, diagnosis, and/or monitoring. In the present study, fluorolabeled peptides derived from the palindromic sequence RWQWRWQWR containing fluorescent probes, such as 2-Aminobenzoyl, 5(6)-Carboxyfluorescein, and Rhodamine B, were obtained. RP-HPLC analysis revealed that the palindromic peptide conjugated to Rhodamine B (RhB-RWQWRWQWR) exhibited the presence of isomers, likely corresponding to the open-ring and spiro-lactam forms of the fluorescent probe. This equilibrium is dependent on the peptide sequence, as the RP-HPLC analysis of dimeric peptide (RhB-RRWQWR-hF-KKLG)₂K-Ahx did not reveal the presence of isomers. The antibacterial activity of the fluorescent peptides depends on the probe attached to the sequence and the bacterial strain tested. Notably, some fluorescent peptides showed activity against reference strains as well as sensitive, resistant, and multidrug-resistant clinical isolates of E. coli, S. aureus, and E. faecalis. Fluorolabeled peptides 1-Abz (MIC = 62 µM), RhB-1 (MIC = 62 µM), and Abz-1 (MIC = 31 µM) exhibited significant activity against clinical isolates of E. coli, S. aureus, and E. faecalis, respectively. The RhB-1 (IC₅₀ = 61 µM), Abz-1 (IC₅₀ = 87 µM), and RhB-2 (IC₅₀ = 35 µM) peptides exhibited a rapid, significant, and concentration-dependent cytotoxic effect on HeLa cells, accompanied by morphological changes characteristic of apoptosis. RhB-1 (IC₅₀ = 18 µM) peptide also exhibited significant cytotoxic activity against breast cancer cells MCF-7. These conjugates remain valuable for elucidating the possible mechanisms of action of these novel anticancer peptides. Rhodamine-labeled peptides displayed cytotoxicity comparable to that of their unlabeled analogues, suggesting that cellular internalization constitutes a critical early step in their mechanism of action. These findings suggest that cell death induced by both unlabeled and fluorolabeled peptides proceeds predominantly via apoptosis and is likely contingent upon peptide internalization. Functionalization at the N-terminal end of the palindromic sequence can be evaluated to develop systems for transporting non-protein molecules into cancer cells. Full article

Ozone (O₃) occurs in nature as a chemical compound made of three oxygen atoms. It is an unstable, highly oxidative gas that rapidly decomposes into oxygen. The therapeutic use of O₃ dates back to the beginning of the 20th century and is currently based on the application of low doses, inducing a moderate oxidative stress that stimulates the antioxidant cellular defenses without causing cell damage. Low O₃ doses also induce anti-inflammatory and regenerative effects, and their anticancer potential is under investigation. In addition, the oxidative properties of O₃ make it an excellent antibacterial, antimycotic, and antiviral agent. Thanks to these properties, O₃ is currently widely used in several medical fields. However, its chemical instability represents an application limit, and ozonated oil is the only stabilized form of medical O₃. In recent years, novel O₃ formulations have been proposed for their sustained and more efficient administration, based on nanotechnology. This review offers an overview of the nanocarriers designed for the delivery of medical O₃, and of their therapeutic applications. The reviewed articles demonstrate that research is active and productive, though it is a rather new entry in the nanotechnological field. Liposomes, nanobubbles, nanoconstructed hydrogels, polymeric nanoparticles, and niosomes were designed to deliver O₃ and have been proven to exert antiseptic, anticancer, and pro-regenerative effects when administered in vitro and in vivo. Improving the therapeutic administration of O₃ through nanocarriers is a just-started challenge, and multiple prospects may be foreseen. Full article

The rise in multidrug-resistant bacterial strains and persistent infections such as Lyme disease caused by Borrelia burgdorferi highlights the need for novel antimicrobial agents. The present study explores the antioxidant, antibacterial, and cytotoxic properties of extracts from submerged mycelial biomass of Fomitopsis pinicola, cultivated in synthetic and lignocellulosic media. Four extracts were obtained using hot water and 80% ethanol. The provided analysis of extracts confirmed the presence of various bioactive compounds, including flavonoids, alkaloids, and polyphenols. All extracts showed dose-dependent antioxidant activity (IC₅₀: 1.9–6.7 mg/mL). Antibacterial tests revealed that Klebsiella pneumoniae was most sensitive, with the L2 extract producing the largest inhibition zone (15.33 ± 0.47 mm), while the strongest bactericidal effect was observed against Acinetobacter baumannii (MBC as low as 0.5 mg/mL for L1). Notably, all extracts significantly reduced the viability of stationary-phase B. burgdorferi cells, with L2 reducing viability to 42 ± 2% at 5 mg/mL, and decreased biofilm mass, especially with S2. Cytotoxicity assays showed minimal effects on NIH 3T3 cells, with slight toxicity in HEK 293 cells for S2 and L1. These results suggest that F. pinicola extracts, particularly ethanolic L2 and S2, may offer promising natural antimicrobial and antioxidant agents for managing resistant infections. Full article

Developing multifunctional wound dressings with excellent mechanical properties, strong tissue adhesion, and efficient antibacterial activity is crucial for promoting wound healing. This study prepared a novel nanocomposite hydrogel dressing based on sodium alginate-polyacrylic acid dual crosslinking networks, incorporating tannic acid-coated cellulose nanocrystals (TA@CNC) and in-situ reduced silver nanoparticles for multifunctional enhancement. The rigid CNC framework significantly improved mechanical properties (elastic modulus of 146 kPa at 1 wt%), while TA catechol groups provided excellent adhesion (36.4 kPa to pigskin, 122% improvement over pure system) through dynamic hydrogen bonding and coordination interactions. TA served as a green reducing agent for uniform AgNPs loading, with CNC negative charges preventing particle aggregation. Antibacterial studies revealed synergistic effects between TA-induced membrane disruption and Ag⁺-triggered reactive oxygen species generation, achieving >99.5% inhibition against Staphylococcus aureus and Escherichia coli. The TA@CNC-regulated porous structure balanced swelling performance and water vapor transmission, facilitating wound exudate management and moist healing. This composite hydrogel successfully integrates mechanical toughness, tissue adhesion, antibacterial activity, and biocompatibility, providing a novel strategy for advanced wound dressing development. Full article

Methicillin-resistant Staphylococcus aureus (MRSA), a multidrug-resistant pathogen, poses a significant threat to global healthcare. This review evaluates the potential of marine algal metabolites as novel antibacterial agents against MRSA. We explore the clinical importance of S. aureus, the emergence of MRSA as a “superbug”, and its resistance mechanisms, including target modification, drug inactivation, efflux pumps, biofilm formation, and quorum sensing. The limitations of conventional antibiotics (e.g., β-lactams, vancomycin, macrolides) are discussed, alongside the promise of algal-derived compounds such as fatty acids, pigments, polysaccharides, terpenoids, and phenolic compounds. These metabolites exhibit potent anti-MRSA activity by disrupting cell division (via FtsZ inhibition), destabilizing membranes, and inhibiting protein synthesis and metabolic pathways, effectively countering multiple resistance mechanisms. Leveraging advances in algal biotechnology, this review highlights the untapped potential of marine algae to drive innovative, sustainable therapeutic strategies against antibiotic resistance. Full article

In this study, we report the development of a novel magnetized coal fly ash-supported nano-silver composite (AgNPs/MCFA) for dual-functional applications in wastewater treatment: the efficient degradation of methyl orange (MO) dye and broad-spectrum antibacterial activity. The composite was synthesized via a facile impregnation–reduction–sintering route, utilizing sodium citrate as both a reducing and stabilizing agent. The AgNPs/MCFA composite was systematically characterized through multiple analytical techniques, including Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), transmission electron microscopy (TEM), X-ray diffraction (XRD), and vibrating sample magnetometry (VSM). The results confirmed the uniform dispersion of AgNPs (average size: 13.97 nm) on the MCFA matrix, where the formation of chemical bonds (Ag-O-Si) contributed to the enhanced stability of the material. Under optimized conditions (0.5 g·L⁻¹ AgNO₃, 250 °C sintering temperature, and 2 h sintering time), AgNPs/MCFA exhibited an exceptional catalytic performance, achieving 99.89% MO degradation within 15 min (pseudo-first-order rate constant k_a = 0.3133 min⁻¹) in the presence of NaBH₄. The composite also demonstrated potent antibacterial efficacy against Escherichia coli (MIC = 0.5 mg·mL⁻¹) and Staphylococcus aureus (MIC = 2 mg·mL⁻¹), attributed to membrane disruption, intracellular content leakage, and reactive oxygen species generation. Remarkably, AgNPs/MCFA retained >90% catalytic and antibacterial efficiency after five reuse cycles, enabled by its magnetic recoverability. By repurposing industrial waste (coal fly ash) as a low-cost carrier, this work provides a sustainable strategy to mitigate nanoparticle aggregation and environmental risks while enhancing multifunctional performance in water remediation. Full article

The integration of nanotechnology and green synthesis strategies provides innovative solutions in biomedicine. This study focuses on the biofabrication of silver nanoparticles (AgNPs) using Corynespora smithii, an endophytic fungus isolated from Bergenia ciliata. The eco-friendly synthesis process employed fungal extracts as reducing and stabilizing agents thereby minimizing the need for hazardous chemicals. The AgNPs demonstrated strong potent biological activities, showcasing significant antioxidant, antibacterial, and anticancer properties. The antibacterial efficacy was demonstrated against various Gram-positive and Gram-negative bacteria, while cytotoxicity on the A549 lung cancer cell line revealed an IC₅₀ value of 10.46 µg/mL. A molecular docking analysis revealed interactions between the major bioactive compound, dimethylsulfoxonium formylmethylide, and the pathogenic proteins, Staphylococcus aureus and Salmonella typhi, displaying moderate binding affinities. Furthermore, the ADME analysis of dimethylsulfoxonium formylmethylide indicated favourable pharmacokinetic properties, including high gastrointestinal absorption, minimal lipophilicity, and low potential for drug–drug interactions, making it a promising candidate for oral drug formulations. These findings further support the compound’s suitability for biomedical applications. This research emphasizes the potential of C. smithii as a sustainable source for synthesizing bioactive nanoparticles, paving the way for their application in developing novel therapeutic agents. This study highlights the significance of harnessing endophytic fungi from medicinal plants for sustainable nanotechnology advancements. Full article

Wounds are undeniably important gateways for pathogens to enter the body. In addition to their detrimental local effects, they can also cause adverse systemic effects. For this reason, developing methods for eradicating pathogens from wounds is a challenging medical issue. Polymers, particularly hydrogels, are one of the more essential materials for designing novel drug-delivery systems, thanks to the ease of tuning their structures. This work exploits this property by utilizing copolymerization, microwave modification, and drug-loading processes to obtain antibacterial gels. Synthesized xylitol-modified glycidyl methacrylate-co-ethyl methacrylate ([P(EMA)-co-(GMA)]-Xyl]) matrices were loaded with bacitracin, gentian violet, furazidine, and brilliant green, used as active pharmaceutical ingredients (APIs). The hydrophilic properties, API release mechanism, and antibacterial properties of the obtained hydrogels against Escherichia coli, Pseudomonas aeruginosa, and Staphylococcus epidermidis containing [P(EMA)-co-(GMA)]-Xyl] were studied. The hydrogels with the APIs efficiently inhibit bacteria growth with low doses of drugs, and our findings are statistically significant, confirmed with ANOVA analysis at p = 0.05. The results confirmed that the proposed system is hydrophilic and has extended the drug-release capabilities of APIs with a controlled burst effect based on [P(EMA)-co-(GMA)]-Xyl] content in the hydrogel. Hydrogels are characterized by the prolonged release of APIs in a very short time (a few minutes). Although the amount of released APIs is about 10%, it still exceeds the minimum inhibitory concentrations of drugs. Several kinetic models (first-order, second-order, Baker–Lonsdale, and Korsmeyer–Peppas) were applied to fit the API release data from the [P(EMA)-co-(GMA)]-Xyl-based hydrogel. The best fit of the Korsmeyer–Peppas kinetic model to the experimental data was determined, and it was confirmed that a diffusion-controlled release mechanism of the APIs from the studied hydrogels is dominant, which is desirable for applications requiring a consistent, controlled release of therapeutic agents. A statistical analysis of API release using Linear Mixed Model was performed, examining the relationship between % mass of API, sample (hydrogels and control), time, sample–time interaction, and variability between individuals. The model fits the data well, as evidenced by the determination coefficients close to 1. The analyzed interactions in the data are reliable and statistically significant (p < 0.001). The outcome of this study suggests that the presented acrylate-based gel is a promising candidate for developing wound dressings. Full article

Background: Endophytic fungi are prolific sources of bioactive metabolites with potential in pharmaceutical and biotechnological applications. Methods: Here, the endophytic fungus, Alternaria alstroemeriae S6, was isolated from Veronica acinifolia (speedwell), and conducted its anti-microbial activities, whole-genome sequencing and metabolome analysis. Results: The ethyl acetate extract of this fungus exhibited strong anti-bacterial activity and the inhibition zones, induced by the fungal extract at 20 mg/mL, reached 16.25 ± 0.5 mm and 26.5 ± 0.5 mm against Gram-positive and Gram-negative bacteria. To unravel the biosynthetic potential for anti-bacterial compounds, whole-genome sequencing was conducted on A. alstroemeriae S6, resulting in a high-quality assembly of 42.93 Mb encoding 13,885 protein-coding genes. Comprehensive functional genome annotation analyses, including gene ontology (GO) terms, clusters of orthologous groups (COGs), Kyoto encyclopedia of genes and genomes (KEGG), carbohydrate-active enzymes (CAZymes), and antibiotics and secondary metabolites analysis shell (antiSMASH) analyses, were performed. According to the antiSMASH analysis, 58 biosynthetic gene clusters (BGCs), including 16 non-ribosomal peptide synthetases (NRPSs), 21 terpene synthases, 12 polyketide synthetases (PKSs), and 9 hybrids, were identified. In addition, succinic acid was identified as the major metabolite within the fungal extract, while 20 minor bioactive compounds were identified through LC-MS/MS-based molecular networking on a GNPS database. Conclusions: These findings support the biotechnological potential of A. alstroemeriae S6 as an alternative producer of succinic acid, as well as novel anti-bacterial agents. Full article

Anaerobes, the oldest evolutionary life forms, have been unexplored for their potential to produce secondary metabolites due to the difficulties observed in their cultivation. Antimicrobials derived from anaerobic bacteria are an emerging and valuable source of novel therapeutic agents. The urgent need for new antimicrobial agents due to rising antibiotic resistance has prompted an investigation into anaerobic bacteria. The conventional method of antimicrobial discovery is based on cultivation and extraction methods. Antibacterial and antifungal substances are produced by anaerobic bacteria, but reports are limited due to oxygen-deficient growth requirements. The genome mining approach revealed the presence of biosynthetic gene clusters involved in various antimicrobial compound synthesis. Thus, the current review is focused on antimicrobials derived from anaerobes to unravel the potential of anaerobic bacteria as an emerging valuable source of therapeutic agents. These substances frequently consist of peptides, lipopeptides, and other secondary metabolites. Many of these antimicrobials have distinct modes of action that may be able to go around established resistance pathways. To this effect, we discuss diverse antimicrobial compounds produced by anaerobic bacteria, their biosynthesis, heterologous production, and activity. The findings suggest that anaerobic bacteria harbor significant biosynthetic potential, warranting further exploration through recombinant production for developing new antibiotics. Full article

This research presents a novel, sustainable, and eco-friendly method for the rapid green synthesis of nanoparticles with antibacterial properties. This method employs steam distillation to extract reducing and stabilizing agents from orange peel waste, followed by ultrasound-assisted synthesis. To the best of our knowledge, this is the first reported integration of these two techniques for nanoparticle production. The extracted materials were then subjected to rigorous characterization through a combination of analytical techniques, including FTIR, HPLC, and TEM. These analytical approaches enabled a comprehensive analysis of the synthesized NPs, revealing their size distribution within the range of 1.5 to 14 nm. Among the synthesized nanomaterials, AgNPs exhibited the most potent antibacterial activity, with statistically significant minimum inhibitory concentrations (MICs) of 16 ppm for E. coli ATCC and 32 ppm for resistant E. coli and E. faecalis strains. This study underscored the promise of valorizing citrus waste for nanomaterial synthesis and introduced a novel, scalable methodology for producing bioactive nanoparticles, promoting a more sustainable technology for this purpose. Notably, this research aligns with United Nations Sustainable Development Goal 12, which promotes responsible consumption and production by transforming organic waste into high-value functional nanomaterials for biomedical and environmental applications. Full article

The green synthesis of zinc oxide nanoparticles (ZnO NPs) using Artemisia absinthium L. extract has gained considerable attention due to its eco-friendly approach and potential applications in food science. This study investigates the synthesis and characterization of Artemisia-mediated ZnO NPs, focusing on their physicochemical properties. The nanoparticles were characterized using ultraviolet–visible spectroscopy (UV–Vis), Fourier transform infrared spectroscopy (FT-IR), field emission scanning electron microscopy (FE-SEM), and energy dispersive X-ray spectroscopy (EDX). Successful synthesis was achieved through a co-precipitation method, resulting in an average particle size of 36.6 nm. The presence of polyphenols and flavonoids in A. absinthium L. extract acted as both a reducing agent and stabilizer for the nanoparticles. The physicochemical characterization revealed strong absorption peaks indicative of ZnO, confirming successful nanoparticle formation. In addition to the structural findings, this study presents novel insights by demonstrating that Artemisia-mediated ZnO NPs possess significantly enhanced antimicrobial activity compared to both pure ZnO NPs and the plant extract alone. The biosynthesized nanoparticles exhibited notably lower minimum inhibitory concentration (MIC) and minimum bactericidal/fungicidal concentration (MBC/MFC) values against Staphylococcus aureus, Escherichia coli, and Candida albicans, suggesting a strong synergistic effect between ZnO and the phytochemicals of A. absinthium L. Thus, the study confirms and quantifies the superior antibacterial potential of Artemisia-derived ZnO NPs, offering promising implications for food, biomedical and pharmaceutical applications. Full article

Background: The global spread of antibiotic-resistant bacteria presents a major public health challenge and necessitates the development of innovative antimicrobial agents. Artificial intelligence (AI)-driven drug discovery has recently enabled the repurposing of existing compounds with novel therapeutic potential. Halicin, originally developed as an anti-diabetic molecule, has been identified through AI screening as a promising antibiotic candidate due to its broad-spectrum activity, including efficacy against multidrug-resistant pathogens. Methods: In this study, the antibacterial activity of halicin was evaluated against a range of clinically relevant multidrug-resistant bacterial strains. Bacterial isolates were first characterized using the agar disk diffusion method with a panel of 22 conventional antibiotics to confirm resistance profiles. The minimum inhibitory concentration (MIC) of halicin was then determined for selected isolates, including Escherichia coli ATCC^® 25922™ and Staphylococcus aureus ATCC^® 29213™, using broth microdilution according to Clinical and Laboratory Standards Institute (CLSI) guidelines. Results: Halicin demonstrated notable antibacterial activity, with MIC values of 16 μg/mL and 32 μg/mL against E. coli ATCC^® 25922™ and S. aureus ATCC^® 29213™, respectively. A dose-dependent inhibition of bacterial growth was observed for the majority of tested isolates, except for Pseudomonas aeruginosa, which exhibited intrinsic resistance. This lack of susceptibility is likely related to reduced outer membrane permeability, limiting the intracellular accumulation of halicin. Conclusions: Our findings support the potential of halicin as a novel antimicrobial agent for the treatment of infections caused by antibiotic-resistant bacteria. However, further investigations, including pharmacokinetic, pharmacodynamic, and toxicity studies, are essential to assess its clinical safety and therapeutic applicability. Full article

The repurposing potential of Efavirenz (EFV), a clinically established non-nucleoside reverse transcriptase inhibitor, was comprehensively evaluated for its in vitro antibacterial effect either alone or in combination with other antibacterial agents on several Gram-positive clinical strains showing different antibiotic resistance profiles. The binding potential assessed by an in silico study included Penicillin-binding proteins (PBPs) and WalK membrane kinase. Despite the relatively high minimum inhibitory concentration (MIC) limiting the use of EFV as a single antibacterial agent, it exhibits significant synergistic activity at sub-MIC levels when paired with various antibiotics against Enterococcus species and Staphylococcus aureus. EFV showed restored sensitivity of β-lactams against Methicillin-resistant S. aureus (MRSA). It increased the effectiveness of antibiotics tested against Methicillin-sensitive S. aureus (MSSA). It also helped to overcome the intrinsic resistance barrier for several antibiotics in Enterococcus spp. In silico binding studies aligned remarkably with experimental antimicrobial testing results and highlighted the potential of EFV to direct the engagement of PBPs with moderate to strong binding affinities (pK_a 5.2–6.1). The dual-site PBP2 binding mechanism emerged as a novel inhibition strategy, potentially circumventing resistance mutations. Special attention should be paid to WalK binding predictions (pK_a = 4.94), referring to the potential of EFV to interfere with essential regulatory pathways controlling cell wall metabolism and virulence factor expression. These findings, in general, suggest the possibility of EFV as a promising lead for the development of new antibacterial agents. Full article