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1.
PLoS One ; 19(5): e0300125, 2024.
Article En | MEDLINE | ID: mdl-38722967

With the increasing problem of antimicrobial drug resistance, the search for new antimicrobial agents has become a crucial task in the field of medicine. Antimicrobial peptides, as a class of naturally occurring antimicrobial agents, possess broad-spectrum antimicrobial activity and lower risk of resistance development. However, traditional screening methods for antimicrobial peptides are inefficient, necessitating the development of an efficient screening model. In this study, we aimed to develop an ensemble learning model for the identification of antimicrobial peptides, named E-CLEAP, based on the Multilayer Perceptron Classifier (MLP Classifier). By considering multiple features, including amino acid composition (AAC) and pseudo amino acid composition (PseAAC) of antimicrobial peptides, we aimed to improve the accuracy and generalization ability of the identification process. To validate the superiority of our model, we employed five-fold cross-validation and compared it with other commonly used methods for antimicrobial peptide identification. In the experimental results on an independent test set, E-CLEAP achieved accuracies of 97.33% and 84% for the AAC and PseAAC features, respectively. The results demonstrated that our model outperformed other methods in all evaluation metrics. The findings of this study highlight the potential of the E-CLEAP model in enhancing the efficiency and accuracy of antimicrobial peptide screening, which holds significant implications for drug development, disease treatment, and biotechnology advancement. Future research can further optimize the model by incorporating additional features and information, as well as validating its reliability on larger datasets and in real-world environments. The source code and all datasets are publicly available at https://github.com/Wangsicheng52/E-CLEAP.


Antimicrobial Peptides , Antimicrobial Peptides/chemistry , Antimicrobial Peptides/pharmacology , Machine Learning , Anti-Infective Agents/pharmacology , Anti-Infective Agents/chemistry , Amino Acids/chemistry
2.
Int J Mol Sci ; 25(9)2024 Apr 24.
Article En | MEDLINE | ID: mdl-38731869

This review provides a comprehensive overview of recent advancements in the design and synthesis of biologically active quaternary ammonium compounds (QACs). The covered scope extends beyond commonly reviewed antimicrobial derivatives to include synthetic agents with antifungal, anticancer, and antiviral properties. Additionally, this review highlights examples of quaternary ammonium compounds exhibiting activity against protozoa and herbicidal effects, as well as analgesic and anesthetic derivatives. The article also embraces the quaternary-ammonium-containing cholinesterase inhibitors and muscle relaxants. QACs, marked by their inherent permanent charge, also find widespread usage across diverse domains such as fabric softeners, hair conditioners, detergents, and disinfectants. The effectiveness of QACs hinges greatly on finding the right equilibrium between hydrophilicity and lipophilicity. The ideal length of the alkyl chain varies according to the unique structure of each QAC and its biological settings. It is expected that this review will provide comprehensive data for medicinal and industrial chemists to design and develop novel QAC-based products.


Quaternary Ammonium Compounds , Quaternary Ammonium Compounds/chemistry , Quaternary Ammonium Compounds/chemical synthesis , Quaternary Ammonium Compounds/pharmacology , Humans , Animals , Anti-Infective Agents/pharmacology , Anti-Infective Agents/chemical synthesis , Anti-Infective Agents/chemistry , Cholinesterase Inhibitors/chemical synthesis , Cholinesterase Inhibitors/pharmacology , Cholinesterase Inhibitors/chemistry
3.
AAPS PharmSciTech ; 25(5): 108, 2024 May 10.
Article En | MEDLINE | ID: mdl-38730090

Wound healing presents a complex physiological process that involves a sequence of events orchestrated by various cellular and molecular mechanisms. In recent years, there has been growing interest in leveraging nanomaterials and peptides to enhance wound healing outcomes. Nanocarriers offer unique properties such as high surface area-to-volume ratio, tunable physicochemical characteristics, and the ability to deliver therapeutic agents in a controlled manner. Similarly, peptides, with their diverse biological activities and low immunogenicity, hold great promise as therapeutics in wound healing applications. In this review, authors explore the potential of peptides as bioactive components in wound healing formulations, focusing on their antimicrobial, anti-inflammatory, and pro-regenerative properties. Despite the significant progress made in this field, several challenges remain, including the need for standardized characterization methods, optimization of biocompatibility and safety profiles, and translation from bench to bedside. Furthermore, developing multifunctional nanomaterial-peptide hybrid systems represents promising avenues for future research. Overall, the integration of nanomaterials made up of natural or synthetic polymers with peptide-based formulations holds tremendous therapeutic potential in advancing the field of wound healing and improving clinical outcomes for patients with acute and chronic wounds.


Drug Carriers , Peptides , Wound Healing , Wound Healing/drug effects , Humans , Peptides/chemistry , Peptides/administration & dosage , Peptides/pharmacology , Drug Carriers/chemistry , Animals , Drug Delivery Systems/methods , Nanostructures/chemistry , Anti-Inflammatory Agents/pharmacology , Anti-Inflammatory Agents/administration & dosage , Anti-Inflammatory Agents/chemistry , Nanoparticles/chemistry , Anti-Infective Agents/administration & dosage , Anti-Infective Agents/pharmacology , Anti-Infective Agents/chemistry
4.
Sci Rep ; 14(1): 10976, 2024 05 14.
Article En | MEDLINE | ID: mdl-38745055

Among the actinomycetes in the rare genera, Micromonospora is of great interest since it has been shown to produce novel therapeutic compounds. Particular emphasis is now on its isolation from plants since its population from soil has been extensively explored. The strain CR3 was isolated as an endophyte from the roots of Hieracium canadense, and it was identified as Micromonospora chokoriensis through 16S gene sequencing and phylogenetic analysis. The in-vitro analysis of its extract revealed it to be active against the clinical isolates of methicillin-resistant Staphylococcus aureus (MRSA) and Candida tropicalis (15 mm). No bioactivity was observed against Gram-negative bacteria, Escherichia coli ATCC 25922, and Klebsiella pneumoniae ATCC 706003. The Micromonospora chokoriensis CR3 extract was also analyzed through the HPLC-DAD-UV-VIS resident database, and it gave a maximum match factor of 997.334 with the specialized metabolite BagremycinA (BagA). The in-silico analysis indicated that BagA strongly interacted with the active site residues of the sterol 14-α demethylase and thymidylate kinase enzymes, with the lowest binding energies of - 9.7 and - 8.3 kcal/mol, respectively. Furthermore, the normal mode analysis indicated that the interaction between these proteins and BagA was stable. The DFT quantum chemical properties depicted BagA to be reasonably reactive with a HOMO-LUMO gap of (ΔE) of 4.390 eV. BagA also passed the drug-likeness test with a synthetic accessibility score of 2.06, whereas Protox-II classified it as a class V toxicity compound with high LD50 of 2644 mg/kg. The current study reports an endophytic actinomycete, M. chokoriensis, associated with H. canadense producing the bioactive metabolite BagA with promising antimicrobial activity, which can be further modified and developed into a safe antimicrobial drug.


Micromonospora , Micromonospora/metabolism , Micromonospora/genetics , Asteraceae/microbiology , Asteraceae/chemistry , Methicillin-Resistant Staphylococcus aureus/drug effects , Microbial Sensitivity Tests , Phylogeny , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/biosynthesis , Anti-Bacterial Agents/chemistry , Computer Simulation , Molecular Docking Simulation , Candida tropicalis/drug effects , Candida tropicalis/metabolism , Density Functional Theory , Anti-Infective Agents/pharmacology , Anti-Infective Agents/chemistry , Plant Roots/microbiology
5.
Org Biomol Chem ; 22(19): 3979-3985, 2024 May 15.
Article En | MEDLINE | ID: mdl-38691112

Two new sesterterpenoids, sesterchaetins A and B (1 and 2), and two new diepoxide polyketides, chaetoketoics A and B (3 and 4), were characterized from the culture extract of Chaetomium globosum SD-347, a fungal strain derived from deep sea-sediment. Their structures and absolute configurations were unambiguously determined by detailed NMR, mass spectra, and X-ray crystallographic analysis. Compounds 1 and 2 contained a distinctive 5/8/6/5 tetracyclic carbon-ring-system, which represented a rarely occurring natural product framework. The new isolates 1-4 exhibited selective antimicrobial activities against human and aquatic pathogenic bacteria and plant-pathogenic fungi.


Chaetomium , Microbial Sensitivity Tests , Polyketides , Sesterterpenes , Chaetomium/chemistry , Polyketides/chemistry , Polyketides/pharmacology , Polyketides/isolation & purification , Sesterterpenes/chemistry , Sesterterpenes/pharmacology , Sesterterpenes/isolation & purification , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/isolation & purification , Geologic Sediments/microbiology , Models, Molecular , Humans , Molecular Structure , Crystallography, X-Ray , Anti-Infective Agents/pharmacology , Anti-Infective Agents/chemistry , Anti-Infective Agents/isolation & purification , Antifungal Agents/pharmacology , Antifungal Agents/chemistry , Antifungal Agents/isolation & purification
6.
Eur J Med Chem ; 271: 116461, 2024 May 05.
Article En | MEDLINE | ID: mdl-38691891

Owing to the global health crisis of resistant pathogenic infections, researchers are emphasizing the importance of novel prevention and control strategies. Existing antimicrobial drugs predominantly target a few pathways, and their widespread use has pervasively increased drug resistance. Therefore, it is imperative to develop new antimicrobial drugs with novel targets and chemical structures. The de novo cysteine biosynthesis pathway, one of the microbial metabolic pathways, plays a crucial role in pathogenicity and drug resistance. This pathway notably differs from that in humans, thereby representing an unexplored target for developing antimicrobial drugs. Herein, we have presented an overview of cysteine biosynthesis pathways and their roles in the pathogenicity of various microorganisms. Additionally, we have investigated the structure and function of enzymes involved in these pathways as well as have discussed drug design strategies and structure-activity relationships of the enzyme inhibitors. This review provides valuable insights for developing novel antimicrobials and offers new avenues to combat drug resistance.


Cysteine , Drug Discovery , Cysteine/metabolism , Cysteine/chemistry , Cysteine/biosynthesis , Humans , Structure-Activity Relationship , Bacteria/drug effects , Bacteria/metabolism , Molecular Structure , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/biosynthesis , Enzyme Inhibitors/pharmacology , Enzyme Inhibitors/chemistry , Microbial Sensitivity Tests , Anti-Infective Agents/pharmacology , Anti-Infective Agents/chemistry , Anti-Infective Agents/metabolism
7.
Sci Rep ; 14(1): 10942, 2024 05 13.
Article En | MEDLINE | ID: mdl-38740839

Pradimicin U is a new dihydrobenzo[a]naphthacenequinone compound found to be active on a screen designed to investigate compounds with antimicrobial activity, produced by the actinomycete designated strain FMUSA5-5T. The strain was isolated from a bio-fertilizer of Musa spp. collected from Suphanburi province, Thailand. The chemotaxonomic characteristics and 16S rRNA gene analysis revealed that strain FMUSA5-5T is a member of the genus Nonomuraea. Low genome-based taxonomic criteria, average nucleotide identity (ANI) (82.8-88.3%), average amino-acid identity (AAI) (79.4-87.3%), and digital DNA-DNA hybridization (dDDH) (29.5-38.5%) values and several phenotypic differences between strain FMUSA5-5T and its closest type strains of the genus Nonomuraea indicated that strain FMUSA5-5T represents a novel species of the genus Nonomuraea and the name Nonomuraea composti sp. nov. is proposed for the strain. The crude extract from the culture broth of strain FMUSA5-5T displayed promising antimicrobial activity against several pathogens and led to the isolation of a novel secondary metabolite, pradimicin U. Interestingly, this compound displayed a broad spectrum of biological activities such as antimalarial activity against Plasmodium falciparum K1 (IC50 value = 3.65 µg/mL), anti-Mycobacterium tuberculosis H37Ra (MIC value = 25.0 µg/mL), anti-Alternaria brassicicola BCC 42724 (MIC value = 25.0 µg/mL), anti-Bacillus cereus ATCC 11778 and anti-Staphylococcus aureus ATCC 29213 (MIC values = 6.25 and 1.56 µg/mL, respectively). Moreover, the compound possessed strong anti-human small cell lung cancer (NCI-H187) activity with IC50 value of 5.69 µg/mL, while cytotoxicity against human breast cancer (MCF-7) and Vero cells was very weak (IC50 values of 52.49 and 21.84 µg/mL, respectively).


Anti-Infective Agents , RNA, Ribosomal, 16S , Humans , Anti-Infective Agents/pharmacology , Anti-Infective Agents/chemistry , RNA, Ribosomal, 16S/genetics , Microbial Sensitivity Tests , Phylogeny , Actinomycetales/genetics , Actinomycetales/isolation & purification , Animals , Thailand , Vero Cells , Musa/microbiology , Plasmodium falciparum/drug effects , Chlorocebus aethiops
8.
Carbohydr Polym ; 337: 122135, 2024 Aug 01.
Article En | MEDLINE | ID: mdl-38710549

The biggest obstacle to treating wound healing continues to be the production of simple, inexpensive wound dressings that satisfy the demands associated with full process of repair at the same time. Herein, a series of injectable composite hydrogels were successfully prepared by a one-pot method by utilizing the Schiff base reaction as well as hydrogen bonding forces between hydroxypropyl chitosan (HCS), ε-poly-l-lysine (EPL), and 2,3,4-trihydroxybenzaldehyde (TBA), and multiple cross-links formed by the reversible coordination between iron (III) and pyrogallol moieties. Notably, hydrogel exhibits excellent physicochemical properties, including injectability, self-healing, water retention, and adhesion, which enable to fill irregular wounds for a long period, providing a suitable moist environment for wound healing. Interestingly, the excellent hemostatic properties of the hydrogel can quickly stop bleeding and avoid the serious sequelae of massive blood loss in acute trauma. Moreover, the powerful antimicrobial and antioxidant properties also protect against bacterial infections and reduce inflammation at the wound site, thus promoting healing at all stages of the wound. The study of biohydrogel with multifunctional integration of wound treatment and smart medical treatment is clarified by this line of research.


Chitosan , Hemostatics , Hydrogels , Polylysine , Wound Healing , Wound Healing/drug effects , Hydrogels/chemistry , Hydrogels/pharmacology , Chitosan/chemistry , Chitosan/pharmacology , Chitosan/analogs & derivatives , Polylysine/chemistry , Polylysine/pharmacology , Animals , Hemostatics/chemistry , Hemostatics/pharmacology , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Mice , Staphylococcus aureus/drug effects , Escherichia coli/drug effects , Humans , Anti-Infective Agents/pharmacology , Anti-Infective Agents/chemistry , Schiff Bases/chemistry , Schiff Bases/pharmacology , Rats
9.
Carbohydr Polym ; 337: 122159, 2024 Aug 01.
Article En | MEDLINE | ID: mdl-38710574

Chitosan and chitosan derivatives can kill pathogenic microorganisms including bacteria and fungi. The antimicrobial activity is dependent on the degree of acetylation, substituent structure, and molecular weight. Over the past four decades, numerous studies have endeavored to elucidate the relationship between molecular weight and the activity against microorganisms. However, investigators have reported divergent and, at times, conflicting conclusions. Here a bilinear equation is proposed, delineating the relationship between antimicrobial activity, defined as log (1/MIC), and the molecular weight of chitosan and chitosan derivatives. Three constants AMin, AMax, and CMW govern the shape of the curve determined by the equation. The constant AMin denotes the minimal activity expected as the molecular weight tends towards zero while AMax represents the maximal activity observed for molecular weights exceeding CMW, the critical molecular weight required for max activity. This equation was applied to analyze data from seven studies conducted between 1984 and 2019, which reported MIC (Minimum Inhibitory Concentration) values against bacteria and fungi for various molecular weights of chitosan and its derivatives. All the 29 datasets exhibited a good fit (R2 ≥ 0.5) and half excellent (R2 ≥ 0.95) fit to the equation. The CMW generally ranged from 4 to 10 KD for datasets with an excellent fit to the equation.


Bacteria , Chitosan , Fungi , Microbial Sensitivity Tests , Molecular Weight , Chitosan/chemistry , Chitosan/pharmacology , Fungi/drug effects , Bacteria/drug effects , Anti-Infective Agents/pharmacology , Anti-Infective Agents/chemistry , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Antifungal Agents/pharmacology , Antifungal Agents/chemistry , Polymers/chemistry , Polymers/pharmacology
10.
Sci Rep ; 14(1): 10228, 2024 05 03.
Article En | MEDLINE | ID: mdl-38702418

Chitosan (CH) exhibits low antimicrobial activity. This study addresses this issue by modifying the chitosan with a sulfonamide derivative, 3-(4-(N,N-dimethylsulfonyl)phenyl)acrylic acid. The structure of the sulfonamide-chitosan derivative (DMS-CH) was confirmed using Fourier transform infrared spectroscopy and Nuclear magnetic resonance. The results of scanning electron microscopy, thermal gravimetric analysis, and X-ray diffraction indicated that the morphology changed to a porous nature, the thermal stability decreased, and the crystallinity increased in the DMS-CH derivative compared to chitosan, respectively. The degree of substitution was calculated from the elemental analysis data and was found to be moderate (42%). The modified chitosan exhibited enhanced antimicrobial properties at low concentrations, with a minimum inhibitory concentration (MIC) of 50 µg/mL observed for B. subtilis and P. aeruginosa, and a value of 25 µg/mL for S. aureus, E. coli, and C. albicans. In the case of native chitosan, the MIC values doubled or more, with 50 µg/mL recorded for E. coli and C. albicans and 100 µg/mL recorded for B. subtilis, S. aureus, and P. aeruginosa. Furthermore, toxicological examinations conducted on MCF-7 (breast adenocarcinoma) cell lines demonstrated that DMS-CH exhibited greater toxicity (IC50 = 225.47 µg/mL) than pure CH, while still maintaining significant safety limits against normal lung fibroblasts (WI-38). Collectively, these results suggest the potential use of the newly modified chitosan in biomedical applications.


Anti-Infective Agents , Chitosan , Microbial Sensitivity Tests , Sulfonamides , Chitosan/chemistry , Chitosan/pharmacology , Humans , Sulfonamides/pharmacology , Sulfonamides/chemistry , Anti-Infective Agents/pharmacology , Anti-Infective Agents/chemistry , Candida albicans/drug effects , Staphylococcus aureus/drug effects , Escherichia coli/drug effects , Spectroscopy, Fourier Transform Infrared , Cell Survival/drug effects , X-Ray Diffraction , MCF-7 Cells
11.
Cryo Letters ; 45(3): 149-157, 2024.
Article En | MEDLINE | ID: mdl-38709186

BACKGROUND: The industrial scale cryo-storage of raw tissue materials requires a robust, low-cost and easy-to-operate method that can facilitate the down-stream process. OBJECTIVE: The study was aimed to develop the multifunctional protective solutions (MPS) for transportation at ambient conditions and also subsequent cryo-storage below -20 degree C of raw porcine hides for tissue engineering and regenerative medicine. MATERIALS AND METHODS: Protective solutions with antimicrobial activity and proteinase-inhibiting activity were developed and tested for its efficacy in preserving the extracellular matrix of porcine dermis from microbial spoilage, proteolytic degradation, freeze damage and excessive dehydration during shipping and cryo-storage. The MPSs contained phosphate-buffered saline with ethylene diamine tetra acetic acid (EDTA) added as chelator and proteinase inhibitor, as well as glycerol or maltodextrin (M180) as cryoprotectants. RESULTS: MPSs prepared with EDTA and glycerol or M180 had significant antimicrobial activity and proteinase-inhibiting activity during the period of shipping and handling. Glycerol and M180 prevented eutectic salt precipitation and excessive freeze dehydration upon cryo-storage of porcine hides. Without glycerol or M180, hides could be freeze-dehydrated to the low hydration at ~0.4 g/g dw, and formed irreversible plications after freezing. A critical hydration (0.8~0.9 g/g dw) was observed for the extracellular matrix of porcine dermis, and dehydration to a lower level could impose enormous stress and potential damage. The soaking of porcine hides in MPSs decreased water content as glycerol and M180 entered into dermis. Upon equilibration, the glycerol content in the tissue was about 94% of the incubating glycerol solution, but the M180 content in the tissue was only about 50% of the incubating M180 solution, indicating that M180 did not get into the entire aqueous domain within dermis. MPSs reduced ice formation and increased the unfrozen water content of porcine raw hides upon cryo-storage. CONCLUSION: MPSs prepared with EDTA and glycerol or M180 have antimicrobial activity and proteinase-inhibiting activity, which can be used for transportation and cryo-storage of raw hides at the industrial scale. Glycerol at 7.5% w/v and M180 at 20% w/v were sufficient to prevent freeze damage and excessive freeze dehydration. Doi.org/10.54680/fr24310110312.


Cryopreservation , Cryoprotective Agents , Regenerative Medicine , Tissue Engineering , Animals , Regenerative Medicine/methods , Swine , Tissue Engineering/methods , Cryopreservation/methods , Cryoprotective Agents/pharmacology , Cryoprotective Agents/chemistry , Edetic Acid/chemistry , Edetic Acid/pharmacology , Protease Inhibitors/pharmacology , Protease Inhibitors/chemistry , Polysaccharides/chemistry , Polysaccharides/pharmacology , Anti-Infective Agents/pharmacology , Anti-Infective Agents/chemistry , Extracellular Matrix/chemistry , Extracellular Matrix/drug effects
12.
BMC Biotechnol ; 24(1): 28, 2024 May 04.
Article En | MEDLINE | ID: mdl-38702622

Scientists know very little about the mechanisms underlying fish skin mucus, despite the fact that it is a component of the immune system. Fish skin mucus is an important component of defence against invasive infections. Recently, Fish skin and its mucus are gaining interest among immunologists. Characterization was done on the obtained silver nanoparticles Ag combined with Clarias gariepinus catfish epidermal mucus proteins (EMP-Ag-NPs) through UV-vis, FTIR, XRD, TEM, and SEM. Ag-NPs ranged in size from 4 to 20 nm, spherical in form and the angles were 38.10°, 44.20°, 64.40°, and 77.20°, Where wavelength change after formation of EMP-Ag-NPs as indicate of dark brown, the broad band recorded at wavelength at 391 nm. Additionally, the antimicrobial, antibiofilm and anticancer activities of EMP-Ag-NPs was assessed. The present results demonstrate high activity against unicellular fungi C. albicans, followed by E. faecalis. Antibiofilm results showed strong activity against both S. aureus and P. aeruginosa pathogens in a dose-dependent manner, without affecting planktonic cell growth. Also, cytotoxicity effect was investigated against normal cells (Vero), breast cancer cells (Mcf7) and hepatic carcinoma (HepG2) cell lines at concentrations (200-6.25 µg/mL) and current results showed highly anticancer effect of Ag-NPs at concentrations 100, 5 and 25 µg/mL exhibited rounding, shrinkage, deformation and granulation of Mcf7 and HepG2 with IC50 19.34 and 31.16 µg/mL respectively while Vero cells appeared rounded at concentration 50 µg/mL and normal shape at concentration 25, 12.5 and 6.25 µg/ml with IC50 35.85 µg/mL. This study evidence the potential efficacy of biologically generated Ag-NPs as a substitute medicinal agent against harmful microorganisms. Furthermore, it highlights their inhibitory effect on cancer cell lines.


Biofilms , Catfishes , Metal Nanoparticles , Silver , Metal Nanoparticles/chemistry , Biofilms/drug effects , Biofilms/growth & development , Silver/chemistry , Silver/pharmacology , Animals , Humans , Mucus/metabolism , Antineoplastic Agents/pharmacology , Antineoplastic Agents/chemistry , Vero Cells , Fish Proteins/pharmacology , Fish Proteins/chemistry , Fish Proteins/metabolism , Chlorocebus aethiops , Cell Line, Tumor , Microbial Sensitivity Tests , Pseudomonas aeruginosa/drug effects , Anti-Infective Agents/pharmacology , Anti-Infective Agents/chemistry , Staphylococcus aureus/drug effects , Staphylococcus aureus/physiology , Candida albicans/drug effects , Epidermis/metabolism
13.
Molecules ; 29(9)2024 Apr 28.
Article En | MEDLINE | ID: mdl-38731531

Actinomycetes have long been recognized as an important source of antibacterial natural products. In recent years, actinomycetes in extreme environments have become one of the main research directions. Streptomyces sp. KN37 was isolated from the cold region of Kanas in Xinjiang. It demonstrated potent antimicrobial activity, but the primary active compounds remained unclear. Therefore, we aimed to combine genomics with traditional isolation methods to obtain bioactive compounds from the strain KN37. Whole-genome sequencing and KEGG enrichment analysis indicated that KN37 possesses the potential for synthesizing secondary metabolites, and 41 biosynthetic gene clusters were predicted, some of which showed high similarity to known gene clusters responsible for the biosynthesis of antimicrobial antibiotics. The traditional isolation methods and activity-guided fractionation were employed to isolate and purify seven compounds with strong bioactivity from the fermentation broth of the strain KN37. These compounds were identified as 4-(Diethylamino)salicylaldehyde (1), 4-Nitrosodiphenylamine (2), N-(2,4-Dimethylphenyl)formamide (3), 4-Nitrocatechol (4), Methylsuccinic acid (5), Phenyllactic acid (6) and 5,6-Dimethylbenzimidazole (7). Moreover, 4-(Diethylamino)salicylaldehyde exhibited the most potent inhibitory effect against Rhizoctonia solani, with an EC50 value of 14.487 mg/L, while 4-Nitrosodiphenylamine showed great antibacterial activity against Erwinia amylovora, with an EC50 value of 5.715 mg/L. This study successfully isolated several highly active antimicrobial compounds from the metabolites of the strain KN37, which could contribute as scaffolds for subsequent chemical synthesis. On the other hand, the newly predicted antibiotic-like substances have not yet been isolated, but they still hold significant research value. They are instructive in the study of active natural product biosynthetic pathways, activation of silent gene clusters, and engineering bacteria construction.


Genomics , Multigene Family , Streptomyces , Streptomyces/genetics , Streptomyces/metabolism , Streptomyces/chemistry , Genomics/methods , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/isolation & purification , Anti-Bacterial Agents/biosynthesis , Microbial Sensitivity Tests , Biological Products/pharmacology , Biological Products/chemistry , Biological Products/isolation & purification , Anti-Infective Agents/pharmacology , Anti-Infective Agents/chemistry , Anti-Infective Agents/isolation & purification , Agriculture/methods , Whole Genome Sequencing
14.
Molecules ; 29(9)2024 Apr 30.
Article En | MEDLINE | ID: mdl-38731558

Given the widespread prevalence of viruses, there is an escalating demand for antimicrobial composites. Although the composite of dialdehyde cellulose and silver nanoparticles (DAC@Ag1) exhibits excellent antibacterial properties, its weak mechanical characteristics hinder its practical applicability. To address this limitation, cellulose nanofibers (CNFs) were initially ammoniated to yield N-CNF, which was subsequently incorporated into DAC@Ag1 as an enhancer, forming DAC@Ag1/N-CNF. We systematically investigated the optimal amount of N-CNF and characterized the DAC@Ag1/N-CNF using FT-IR, XPS, and XRD analyses to evaluate its additional properties. Notably, the optimal mass ratio of N-CNF to DAC@Ag1 was found to be 5:5, resulting in a substantial enhancement in mechanical properties, with a 139.8% increase in tensile elongation and a 33.1% increase in strength, reaching 10% and 125.24 MPa, respectively, compared to DAC@Ag1 alone. Furthermore, the inhibition zones against Escherichia coli and Staphylococcus aureus were significantly expanded to 7.9 mm and 15.9 mm, respectively, surpassing those of DAC@Ag1 alone by 154.8% and 467.9%, indicating remarkable improvements in antimicrobial efficacy. Mechanism analysis highlighted synergistic effects from chemical covalent bonding and hydrogen bonding in the DAC@Ag1/N-CNF, enhancing the mechanical and antimicrobial properties significantly. The addition of N-CNF markedly augmented the properties of the composite film, thereby facilitating its broader application in the antimicrobial field.


Cellulose , Escherichia coli , Metal Nanoparticles , Silver , Staphylococcus aureus , Silver/chemistry , Metal Nanoparticles/chemistry , Escherichia coli/drug effects , Staphylococcus aureus/drug effects , Cellulose/chemistry , Cellulose/analogs & derivatives , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Nanofibers/chemistry , Nanocomposites/chemistry , Microbial Sensitivity Tests , Anti-Infective Agents/chemistry , Anti-Infective Agents/pharmacology , Spectroscopy, Fourier Transform Infrared
15.
Molecules ; 29(9)2024 May 03.
Article En | MEDLINE | ID: mdl-38731619

This study aims to investigate the vegetative buds from Picea abies (spruce), naturally found in a central region of Romania, through a comprehensive analysis of the chemical composition to identify bioactive compounds responsible for pharmacological properties. Using HPLC/derivatization technique of GC-MS and quantitative spectrophotometric assays, the phenolic profile, and main components of an ethanolic extract from the buds were investigated. The essential oil was characterized by GC-MS. Moreover, the antioxidant activity with the DPPH method, and the antimicrobial activity were tested. Heavy metal detection was performed by graphite furnace atomic absorption spectrometry. The main components of the alcoholic extract were astragalin, quercetin, kaempferol, shikimic acid, and quinic acid. A total content of 25.32 ± 2.65 mg gallic acid equivalent per gram of dry plant (mg GAE/g DW) and of 10.54 ± 0.083 mg rutin equivalents/g of dry plant (mg RE/g DW) were found. The essential oil had D-limonene, α-cadinol, δ-cadinene, 13-epimanool, and δ-3-carene as predominant components. The spruce vegetative buds exhibited significant antioxidant activity (IC50 of 53 µg/mL) and antimicrobial effects against Staphylococcus aureus. Furthermore, concentrations of heavy metals Pb and Cd were below detection limits, suggesting that the material was free from potentially harmful contaminants. The results confirmed the potential of this indigenous species to be used as a source of compounds with pharmacological utilities.


Anti-Infective Agents , Antioxidants , Oils, Volatile , Phytochemicals , Picea , Plant Extracts , Picea/chemistry , Antioxidants/pharmacology , Antioxidants/chemistry , Phytochemicals/pharmacology , Phytochemicals/chemistry , Anti-Infective Agents/pharmacology , Anti-Infective Agents/chemistry , Plant Extracts/pharmacology , Plant Extracts/chemistry , Oils, Volatile/pharmacology , Oils, Volatile/chemistry , Microbial Sensitivity Tests , Gas Chromatography-Mass Spectrometry , Romania , Phenols/analysis , Phenols/pharmacology , Phenols/chemistry
16.
Int J Mol Sci ; 25(9)2024 May 01.
Article En | MEDLINE | ID: mdl-38732168

Antimicrobial resistance (AMR) poses an emanating threat to humanity's future. The effectiveness of commonly used antibiotics against microbial infections is declining at an alarming rate. As a result, morbidity and mortality rates are soaring, particularly among immunocompromised populations. Exploring alternative solutions, such as medicinal plants and iodine, shows promise in combating resistant pathogens. Such antimicrobials could effectively inhibit microbial proliferation through synergistic combinations. In our study, we prepared a formulation consisting of Aloe barbadensis Miller (AV), Thymol, iodine (I2), and polyvinylpyrrolidone (PVP). Various analytical methods including SEM/EDS, UV-vis, Raman, FTIR, and XRD were carried out to verify the purity, composition, and morphology of AV-PVP-Thymol-I2. We evaluated the inhibitory effects of this formulation against 10 selected reference strains using impregnated sterile discs, surgical sutures, gauze bandages, surgical face masks, and KN95 masks. The antimicrobial properties of AV-PVP-Thymol-I2 were assessed through disc diffusion methods against 10 reference strains in comparison with two common antibiotics. The 25-month-old formulation exhibited slightly lower inhibitory zones, indicating changes in the sustained-iodine-release reservoir. Our findings confirm AV-PVP-Thymol-I2 as a potent antifungal and antibacterial agent against the reference strains, demonstrating particularly strong inhibitory action on surgical sutures, cotton bandages, and face masks. These results enable the potential use of the formulation AV-PVP-Thymol-I2 as a promising antimicrobial agent against wound infections and as a spray-on contact-killing agent.


Microbial Sensitivity Tests , Thymol , Thymol/pharmacology , Thymol/chemistry , Iodine/chemistry , Iodine/pharmacology , Anti-Infective Agents/pharmacology , Anti-Infective Agents/chemistry , Aloe/chemistry , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Humans , Drug Compounding/methods
17.
Bol. latinoam. Caribe plantas med. aromát ; 23(3): 437-447, mayo 2024. tab
Article Es | LILACS | ID: biblio-1538171

The aim of this study was to optimize by response surface design, the extraction of the leaf essential oil (EO) from Minthostachys mollis [HBK] Griseb., grown in Ecuador, using steam distillation. The factors used were extraction time (XTIE) of 60, 105 and 150 min and plant material/water ratio (XRMA) of 1:3, 1:4 and 1:5. The optimal combination was reached with XRMA 1:5 and XTIE 150 min, obtaining a process yield of 0.67%. The chemical composition of the EO analyzed by GC - MS was determined, where the main compounds were carvacryl acetate (44.01%), carvacrol (16.51%) and menthone (8.20%). The anti oxidant capacity of EO was evaluated using the FRAP and ABTS methodologies, with an IC 50 243.21 µmol Fe 2+ /g and 0.12 mg/mL, respectively. In addition, the antimicrobial activity of EO was found against Pseudomonas aeruginosa , Salmonella enterica , Escherich ia coli and Staphylococcus aureus .


El objetivo del estudio fue optimizar, mediante un diseño de superficie respuesta, la extracción d el aceite esencial (AE) de hojas de Minthostachys mollis [HBK] Griseb. del Ecuador, mediante destilación por arrastre de vapor. Los factores fueron el tiempo de extracción (XTIE) de 60, 105 y 150 min, y relación de material vegetal/ agua destilada (XRMA) d e 1:3, 1:4 y 1:5. La combinación óptima se logró con XTIE 150 min y XRMA 1:5 para un rendimiento de 0,67%. Se determinó la composición química del AE por GC - MS donde los compuestos mayoritarios fueron acetato de carvacrilo (44,01%), carvacrol (16,51%) y me ntona (8,20%). Se evaluó la capacidad antioxidante del AE por las metodologías FRAP y ABTS, con CI 50 de 243,21 µmol Fe 2+ /g y 0,12 mg/mL, respectivamente. Además, se demostró la actividad antimicrobiana contra Pseudomonas aeruginosa , Salmonella enterica , Es cherichia coli y Staphylococcus aureus .


Oils, Volatile/pharmacology , Oils, Volatile/chemistry , Anti-Infective Agents/chemistry , Plant Leaves/chemistry , Lamiaceae/metabolism , Lamiaceae/chemistry , Ecuador
18.
Free Radic Biol Med ; 219: 104-111, 2024 Jul.
Article En | MEDLINE | ID: mdl-38608822

Hypothiocyanous acid (HOSCN) is an endogenous oxidant produced by peroxidase oxidation of thiocyanate (SCN-), an ubiquitous sulfur-containing pseudohalide synthesized from cyanide. HOSCN serves as a potent microbicidal agent against pathogenic bacteria, viruses, and fungi, functioning through thiol-targeting mechanisms, independent of currently approved antimicrobials. Additionally, SCN- reacts with hypochlorous acid (HOCl), a highly reactive oxidant produced by myeloperoxidase (MPO) at sites of inflammation, also producing HOSCN. This imparts both antioxidant and antimicrobial potential to SCN-. In this review, we discuss roles of HOSCN/SCN- in immunity and potential therapeutic implications for combating infections.


Thiocyanates , Thiocyanates/therapeutic use , Thiocyanates/chemistry , Thiocyanates/pharmacology , Thiocyanates/metabolism , Humans , Animals , Anti-Infective Agents/pharmacology , Anti-Infective Agents/therapeutic use , Anti-Infective Agents/chemistry , Antioxidants/pharmacology , Antioxidants/therapeutic use , Peroxidase/metabolism , Oxidation-Reduction , Hypochlorous Acid/metabolism , Hypochlorous Acid/therapeutic use , Hypochlorous Acid/chemistry , Respiratory Tract Infections/drug therapy , Respiratory Tract Infections/microbiology
19.
Colloids Surf B Biointerfaces ; 238: 113889, 2024 Jun.
Article En | MEDLINE | ID: mdl-38574404

A novel core-shell with a tetradecyl dimethyl benzyl ammonium chloride-modified montmorillonite (TDMBA/MMT) interlayer silk fibroin (SF)/poly(lactic acid) (PLLA) nanofibrous membrane was fabricated using a simple conventional electrospinning method. Scanning electron microscopy and pore size analyses revealed that this core-shell with TDMBA/MMT interlayer maintained its nanofibrous morphology and larger pore structure more successfully than SF/PLLA nanofibrous membranes after treatment with 75% ethanol vapor. Transmission electron microscopy and energy-dispersive X-ray spectroscopy analyses testified that the SF/PLLA-TDMBA/MMT nanofibers exhibited a core-shell with an interlayer structure, with SF/PLLA in the core-shell layer and TDMBA/MMT in the interlayer. The formation of a core-shell with interlayer nanofibers was primarily attributed to the uniform dispersion of TDMBA/MMT nanosheets in a solution owing to its exfoliation using hexafluoroisopropanol and then preparing a stable spinning solution similar to an emulsion. Compared to SF/PLLA nanofibrous membranes, the core-shell structure with TDMBA/MMT interlayers of SF/PLLA nanofibrous membranes exhibited enhanced hydrophilicity, thermal stability, mechanical properties as well as improved and long-lasting antimicrobial performance against Escherichia coli and Staphylococcus aureus without cytotoxicity.


Bentonite , Escherichia coli , Nanofibers , Staphylococcus aureus , Bentonite/chemistry , Bentonite/pharmacology , Nanofibers/chemistry , Staphylococcus aureus/drug effects , Escherichia coli/drug effects , Microbial Sensitivity Tests , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/chemical synthesis , Quaternary Ammonium Compounds/chemistry , Quaternary Ammonium Compounds/pharmacology , Fibroins/chemistry , Fibroins/pharmacology , Polyesters/chemistry , Polyesters/pharmacology , Membranes, Artificial , Anti-Infective Agents/pharmacology , Anti-Infective Agents/chemistry , Mice , Animals
20.
Colloids Surf B Biointerfaces ; 238: 113912, 2024 Jun.
Article En | MEDLINE | ID: mdl-38608465

The potential application of colloidal polyaniline (PANI) as an antimicrobial is limited by challenges related to solubility in common organic solvents, scalability, and antimicrobial potency. To address these limitations, we introduced a functionalized PANI (fPANI) with carboxyl groups through the polymerisation of aniline and 3-aminobenzoic acid in a 1:1 molar ratio. fPANI is more soluble than PANI which was determined using a qualitative study. We further enhanced the solubility and antimicrobial activity of fPANI by incorporating Ag nanoparticles onto the synthesized fPANI colloid via direct addition of 10 mM AgNO3. The improved solubility can be attributed to an approximately 3-fold reduction in size of particles. Mean particle sizes are measured at 1322 nm for fPANI colloid and 473 nm for fPANI-Ag colloid, showing a high dispersion and deagglomeration effect from Ag nanoparticles. Antimicrobial tests demonstrated that fPANI-Ag colloids exhibited superior potency against Gram-positive Staphylococcus aureus, Gram-negative Escherichia coli, and Bacteriophage PhiX 174 when compared to fPANI alone. The minimum bactericidal concentration (MBC) and minimum virucidal concentration (MVC) values were halved for fPANI-Ag compared to fPANI colloid and attributed to the combination of Ag nanoparticles with the fPANI polymer. The antimicrobial fPANI-Ag colloid presented in this study shows promising results, and further exploration into scale-up can be pursued for potential biomedical applications.


Aniline Compounds , Colloids , Escherichia coli , Microbial Sensitivity Tests , Particle Size , Silver , Staphylococcus aureus , Aniline Compounds/chemistry , Aniline Compounds/pharmacology , Aniline Compounds/chemical synthesis , Colloids/chemistry , Escherichia coli/drug effects , Staphylococcus aureus/drug effects , Silver/chemistry , Silver/pharmacology , Metal Nanoparticles/chemistry , Anti-Infective Agents/pharmacology , Anti-Infective Agents/chemistry , Anti-Infective Agents/chemical synthesis , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/chemical synthesis , Solubility
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