Search Results (441)

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

The worldwide increase in antifungal resistance, particularly in Candida sp., requires the exploration of novel therapeutic agents. Natural compounds have been a rich source of antimicrobial molecules, where peptides constitute the class of the most bioactive components. Therefore, this study looks into the target-specific binding efficacy of insect-derived antifungal peptides (n = 37) as possible alternatives to traditional antifungal treatments. Using computational methods, namely the HPEPDOCK and HDOCK platforms, molecular docking was performed to evaluate the interactions between selected key fungal targets, lanosterol 14-demethylase, or LDM (PDB ID: 5V5Z), secreted aspartic proteinase-5, or Sap-5 (PDB ID: 2QZX), N-myristoyl transferase, or NMT (PDB ID: 1NMT), and dihydrofolate reductase, or DHFR, of C. albicans. The three-dimensional peptide structure was modelled through the PEP-FOLD 3.5 tool. Further, we predicted the physicochemical properties of these peptides through the ProtParam and PEPTIDE 2.0 tools to assess their drug-likeness and potential for therapeutic applications. In silico results show that Blap-6 from Blaps rhynchopeter and Gomesin from Acanthoscurria gomesiana have the most antifungal potential against all four targeted proteins in Candida sp. Additionally, a molecular dynamics simulation study of LDM-Blap-6 was carried out at 100 nanoseconds. The overall predictions showed that both have strong binding abilities and are good candidates for drug development. In in vitro studies, Gomesin achieved complete biofilm eradication in three out of four Candida species, while Blap-6 showed moderate but consistent reduction across all species. C. tropicalis demonstrated relative resistance to complete eradication by both peptides. The present study provides evidence to support the antifungal activity of certain insect peptides, with potential to be used as alternative drugs or as a template for a new synthetic or modified peptide in pursuit of effective therapies against Candida spp. Full article

Food waste has emerged as a critical worldwide concern, resulting in environmental deterioration and economic detriment. Bio-based natural polymer coatings and films have emerged as a sustainable solution to food preservation challenges, particularly in reducing postharvest losses and extending shelf life. Compared to their synthetic counterparts, these polymers, such as chitosan, starch, cellulose, proteins, and alginate, are derived from renewable sources that are biodegradable, safe, and functional. Within this context, this review examines the various bio-based natural polymer coatings and films as biodegradable, edible alternatives to conventional packaging solutions. It examines the different fabrication methods, like solution casting, electrospinning, and spray coating, and incorporates antimicrobial agents to enhance performance. Emphasis is placed on their mechanical, barrier, and antimicrobial properties, their application in preserving fresh produce, how they promote food safety and environmental sustainability, and accompanying limitations. This review highlights the importance of bio-based natural polymer coatings and films as a promising, eco-friendly solution to enhancing food quality, safety, and shelf life while addressing global sustainability challenges. Full article

Background/objectives: The increasing prevalence of multidrug-resistant (MDR) bacteria, particularly Klebsiella pneumoniae, calls for the development of new antimicrobial agents. This study investigates a series of fluorinated azolium salts and their rhodium(I) complexes for antibacterial activity against clinical and reference strains of K. pneumoniae. Methods: Eleven fluorinated azolium salts and their corresponding Rh(I) complexes (22 compounds total) were synthesized and tested against several K. pneumoniae strains, including three MDR clinical isolates (U–13685, H–9871, U–13815) and ATCC reference strains. Minimum inhibitory concentrations (MICs) were determined. In silico ADMET analyses were conducted to evaluate intestinal absorption, oral bioavailability, Caco-2 permeability, carcinogenicity, solubility, and synthetic accessibility. Results: Among the Rh(I) complexes, Rh–1, Rh–3, and Rh–11 showed activity against the three MDR isolates (MIC = 62.5–250 µg/mL), while Rh–1, Rh–4, Rh–6, and Rh–11 were active against all ATCC strains (MIC = 3.9–250 µg/mL). The corresponding azolium salts displayed weak or no activity, highlighting the critical role of the metal center. ADMET predictions indicated that most Rh complexes had good intestinal absorption, and all except Rh–3, Rh–4, and Rh–9 were predicted to be orally bioavailable. Compounds Rh–1 to Rh–7 showed Caco-2 permeability, and all were classified as non-carcinogenic. Rh–8 to Rh–11 exhibited lower solubility and synthetic accessibility. Conclusions: The results underscore the potential of fluorinated Rh(I) complexes as antibacterial agents against MDR K. pneumoniae, with Rh–1 and Rh–11 emerging as promising leads based on activity and favorable predicted pharmacokinetics. Full article

Bacteriophages (phages), the most abundant biological entities on Earth, have long served as both model systems and therapeutic tools. Recent advances in synthetic biology and genetic engineering have revolutionized the capacity to tailor phages with enhanced functionality beyond their natural capabilities. This review outlines the current landscape of synthetic and functional engineering of phages, encompassing both in-vivo and in-vitro strategies. We describe in-vivo approaches such as phage recombineering systems, CRISPR-Cas-assisted editing, and bacterial retron-based methods, as well as synthetic assembly platforms including yeast-based artificial chromosomes, Gibson, Golden Gate, and iPac assemblies. In addition, we explore in-vitro rebooting using TXTL (transcription–translation) systems, which offer a flexible alternative to cell-based rebooting but are less effective for large genomes or structurally complex phages. Special focus is given to the design of customized phages for targeted applications, including host range expansion via receptor-binding protein modifications, delivery of antimicrobial proteins or CRISPR payloads, and the construction of biocontained, non-replicative capsid systems for safe clinical use. Through illustrative examples, we highlight how these technologies enable the transformation of phages into programmable bactericidal agents, precision diagnostic tools, and drug delivery vehicles. Together, these advances establish a powerful foundation for next-generation antimicrobial platforms and synthetic microbiology. Full article

Benzothiazole derivatives have emerged as being highly significant in drug discovery due to their versatile biological activities and structural adaptability. Incorporating nitrogen and sulfur, this fused heterocyclic scaffold exhibits wide-ranging pharmacological properties, including anticancer, antimicrobial, anti-inflammatory, antidiabetic, neuroprotective, and diagnostic applications. A diverse set of clinically approved and investigational compounds, such as flutemetamol for Alzheimer’s diagnosis, riluzole for ALS, and quizartinib for AML, illustrates the scaffold’s therapeutic potential in varied applications. These agents act via mechanisms such as enzyme inhibition, receptor modulation, and amyloid imaging, demonstrating the scaffold’s high binding affinity and target specificity. Advances in synthetic strategies and our understanding of structure–activity relationships (SARs) continue to drive the development of novel benzothiazole-based therapeutics with improved potency, selectivity, and safety profiles. We also emphasize recent in vitro and in vivo studies, including drug candidates in clinical trials, to provide a comprehensive perspective on the therapeutic potential of benzothiazole-based compounds in modern drug discovery. This review brings together recent progress to help guide the development of new benzothiazole-based compounds for future therapeutic applications. Full article

Metal chelation to bioactive small molecules is a well-established strategy to enhance the biological activity of the resulting complexes. Among the widely explored structural motifs, the combination of prominent metal centers with naturally inspired derivatives has attracted considerable attention. One such promising platform is the flavone scaffold, derived from flavonoids and studied since ancient times. Flavones are plant-derived compounds known for their diverse biological activities and health benefits. They exhibit significant structural variability, primarily through backbone modifications such as hydroxylation. Importantly, coordination of metal ions to hydroxylated flavone cores often improves their natural bioactivities, including anticancer and antimicrobial effects. In this review, we summarize transition metal complexes incorporating hydroxyflavone (OH–F) ligands reported over the past 15 years. We provide a concise overview of synthetic approaches and structural characterization, with a particular emphasis on coordination modes (e.g., maltol-type, acetylacetonate-type, catechol-type, and others). Furthermore, we discuss biological evaluation results, especially anticancer and antimicrobial studies, to highlight the therapeutic potential of these complexes. Finally, we suggest directions for the future development of metal-based agents bearing hydroxyflavone moieties through several critical points in terms of the accuracy, reproducibility, and relevance of biological studies involving metal-based compounds. Full article

Essential oils (EOs) represent natural bioactive agents with broad applications; however, their industrial utilization is often hampered by inherent volatility and instability, which current encapsulation methods struggle to overcome due to limitations such as reliance on synthetic surfactants. Proteins, owing to their amphiphilic nature, serve as materials for EOs microencapsulation, particularly when chemically modified. Building upon our previous work demonstrating improved emulsifying properties of hemp seed protein isolate (HPI) through covalent modification with gallic acid (GA), this study investigated its efficacy for essential oil encapsulation. This study developed a novel microencapsulation system utilizing conjugates of HPI and GA for stabilizing six essential oils (lemon, grapefruit, camellia, fragrans, oregano, and mustard). The microcapsules exhibited encapsulation efficiencies (EE) ranging from 40% to 88%, with oregano oil demonstrating superior performance due to carvacrol’s amphiphilic surfactant properties. Advanced characterization techniques revealed that high-EE microcapsules displayed compact morphologies, enhanced thermal stability, and reduced surface oil localization. Release kinetics followed either the Peppas or Weibull model, with oregano microcapsules achieving sustained release via matrix erosion mechanisms. Antioxidant assays and antimicrobial tests demonstrated multifunctional efficacy, where oregano microcapsules exhibited the highest radical scavenging and antimicrobial activity. These findings establish HPI-GA conjugates as unique dual-functional emulsifier-encapsulants, offering a sustainable and effective platform to enhance EO stability and bioactivity, particularly for applications in food preservation and pharmaceutical formulations. Full article

The fashion industry is widely recognized for its environmental challenges, but the health impacts related to textile toxicity remain significantly underexplored. Beyond the well-known issues of pollution and resource depletion, modern clothing often harbors a hidden threat: hazardous chemicals embedded within fabrics. These include dyes containing heavy metals, antimicrobial agents that foster bacterial resistance, and synthetic fibers that release microplastics. Unlike environmental discussions, the dialogue around the direct and long-term health effects of these substances is still limited. This entry addresses critical yet often-overlooked concerns, such as how chemicals in textiles contribute to chronic skin conditions, hormonal disruptions, and even carcinogenic risks. It also examines the proliferation of bacteria in synthetic garments, leading to dermatological infections and rapid fabric degradation. Furthermore, the globalized nature of production masks the contamination risks transferred from producer to consumer countries. Through an interdisciplinary approach, this entry highlights the urgent need for integrating scientific innovation, stringent regulation, and consumer awareness to mitigate health hazards in fashion. It calls for the adoption of safer textile technologies, sustainable materials, and transparent production practices, paving the way for a fashion future that prioritizes human health as much as environmental sustainability. Full article

Background/Objectives: The rise of antibiotic-resistant bacteria presents a major global health challenge, highlighting the need for novel antimicrobial agents such as antimicrobial peptides (AMPs). AMPs are promising due to their broad-spectrum activity, membrane-disruptive mechanisms, and low development of resistance. This study aimed to design and evaluate novel AMPs derived from a synthetic parent peptide (PEP-38). Methods: Novel peptides were designed using bioinformatics tools, including CAMP_R3 and Peptide Ranker. Their antimicrobial potential was validated through in vitro assays, including bacterial susceptibility, antibiofilm activity, cytotoxicity, hemolysis, and time–kill kinetics. Results: Among the designed peptides, Hel-4K-12K showed potent activity against both Gram-positive and Gram-negative bacteria, with MICs ranging from 3.125 to 6.25 µM. It also effectively eradicated biofilms of resistant Staphylococcus aureus at an MBEC of 6.25 µM. Time–kill assays confirmed rapid bactericidal action, achieving complete bacterial elimination within one hour at its MIC. Moreover, Hel-4K-12K exhibited low toxicity toward mammalian MDCK cells (>82% viability at MIC) and minimal hemolytic activity on human erythrocytes. Conclusions: Hel-4K-12K demonstrates strong antibacterial and antibiofilm activities with a favorable safety profile, indicating its potential as a therapeutic candidate for treating infections caused by resistant bacteria. These findings support further development of this peptide as a basis for new antimicrobial drug strategies. In addition to its promising in vitro profile, future studies will investigate Hel-4K-12K in animal models and evaluate strategies for attaining stable formulations, such as peptide encapsulation or PEGylation. These steps are critical to ensure its therapeutic viability in systemic applications. Full article

Increasing multidrug resistance in Neisseria gonorrhoeae poses a serious and escalating public health crisis. The World Health Organization has classified N. gonorrhoeae as a high-priority pathogen for developing new antimicrobials. Natural products provide a promising avenue for antimicrobial discovery, serving as direct therapeutic agents or prototypes for novel drug development. Among these, gibbilimbol B, a compound isolated from Piper malacophyllum, is particularly attractive due to its biological potential and simple structure. In this study, eight synthetic phenylalkylamides (1–8) inspired by gibbilimbol B were synthesized and evaluated for their antibacterial activity against N. gonorrhoeae. The in vitro bacterial assays revealed that these compounds exhibit notable antibacterial activity, including against resistant strains selected from the CDC/FDA antimicrobial panel (strains AR-173, AR-174, AR-187, and AR-200). All synthesized compounds demonstrated superior efficacy in killing N. gonorrhoeae compared to gibbilimbol B. Notably, compound 8 [(E)-4-chloro-N-(oct-4-en-1-yl)benzamide] showed an MBC50 of 6.25 µM, representing a four-fold improvement in bactericidal activity over the natural compound. This study represents the first exploration of gibbilimbol analogs for antibacterial applications, highlighting the novelty of the work and paving the way for the development of new antibacterial agents. Full article

Flavonoids and chalcones, widely recognised for their diverse biological activities, have garnered attention due to their potential therapeutic applications. This review discusses fluorinated flavonoids and chalcones, focusing on their prospective anti-inflammatory, antidiabetic, anticancer, antiosteoporotic, cardioprotective, neuroprotective, hepatoprotective, antimicrobial, and antiparasitic applications. The enhanced biological activities of fluorinated derivatives, particularly the antibacterial, antiviral, and anticancer properties, are attributed to the introduction of fluorine groups, which increase lipophilicity and metabolic stability. Key findings indicate that fluorinated flavonoids and chalcones exhibit synergistic effects with antibiotics, inhibit bacterial efflux pumps, and reveal potent antiviral and anticancer properties. However, challenges such as cytotoxicity and structural optimisation have to be addressed. The synthesis of fluorinated flavonoids and chalcones is discussed, with emphasis on various synthetic methods such as condensation and cyclisation reactions starting from fluorinated precursors, as well as fluorination strategies, including the use of molecular fluorine or fluorinating agents. Fluorinated flavonoids and chalcones represent candidates for therapeutic development and have the potential to overcome drug resistance. However, further studies are necessary to adjust their pharmacological profiles. Full article

Proline-rich antimicrobial peptides (PrAMPs) primarily exert their antimicrobial effects intracellularly, inhibiting protein synthesis. B7-005, a synthetic 16-amino acid PrAMP, has a broader antimicrobial spectrum compared to native counterparts, despite shorter PrAMPs typically exhibiting reduced activity. This study aimed to enhance B7-005’s potency by extending it with 6 or 11 amino acids derived from the C-terminal sequences of cetacean Tur1A and Lip1 PrAMPs, as well as bovine Bac7(1-35). Six chimeric derivatives were evaluated for antimicrobial and bactericidal potency, cytotoxicity, bacterial membrane permeabilization, and in vitro inhibition of protein synthesis. Extending B7-005 with sequences from other PrAMPs increased its activity against most ESKAPE+E pathogens, reducing minimum inhibitory concentration (MIC) values by 2- to 8-fold, with notable differences among bacterial species, without increasing cytotoxicity toward the A549 cell line. All chimeras retained the ability to inhibit protein synthesis in Escherichia coli and to modestly perturb the E. coli membranes like B7-005. These novel chimeric PrAMPs, particularly the 22-mer derivatives, hold promise for developing new antimicrobial agents. The study also highlights variability in bacterial responses to PrAMPs and underscores how minor sequence differences can significantly impact efficacy against specific microorganisms. PrAMPs thus represent a valuable scaffold to rationally design derivatives targeting high-priority pathogens. Full article

Natural phenolic substances have emerged as promising alternatives to synthetic antimicrobials in both agriculture and the food industry, where concerns over microbial resistance and chemical residues are rising. This review provides a comprehensive overview of the current literature, highlighting the potential of these compounds as effective antimicrobial agents. A systematic evaluation of in vitro and in vivo studies was conducted, focusing on the efficacy of various phenolic compounds against a range of pathogens. The analysis revealed that natural phenolics not only inhibit microbial growth but also enhance the shelf life and safety of food products and protect crops from disease. Moreover, although laboratory results are promising, the translation of these findings into practical applications requires further investigation. Overall, the evidence supports the potential for natural phenolic substances to serve as integral components in sustainable agriculture and food preservation strategies. Full article

Phytopathogenic fungi and bacteria pose a serious threat to global agriculture, leading to significant economic losses and potential health risks. Consequently, the search for natural alternatives to synthetic agrochemicals has garnered increasing scientific attention, with plant extracts emerging as promising environmentally friendly solutions. In this context, the surface extract of Salvia discolor, obtained using dichloromethane, was analyzed for its bioactive potential. Chemical profiling revealed a rich composition of terpenoids and flavonoids. The antimicrobial potential of the ground extract was evaluated against nine phytopathogenic fungi (Alternaria solani, Botrytis cinerea, Colletotrichum lindemuthianum, Fusarium solani, Fusarium oxysporum f. sp. lactucae race 1, Phoma betae, Phaeomoniella chlamydospora, Pythium dissotocum, and Stemphylium sp.), and two phytopathogenic bacteria (Clavibacter michiganesis subsp. michiganesis and Pectobacterium carotovorum subsp. carotovorum), selected from common pathogens of agricultural interest. Complete inhibition of P. chlamydospora at 1000 µg mL⁻¹ and strong activity against P. dissotocum, F. solani and B. cinerea was observed, and low inhibition (<40%) against C. lindemuthianum and F. oxysporum f. sp. lactucae race 1. However, the extract showed promising results in the post-harvest protection of tomatoes against gray mold. Moderate antibacterial activity was seen against C. michiganensis subsp. michiganensis. These findings indicate that S. discolor extract has the potential to serve as an effective natural crop protection agent, though further optimization may be needed for broader application. Full article