Potent Antifungal Activity Research Articles

Genomic and Untargeted Metabolomic Analysis of Secondary Metabolites in the Streptomyces griseoaurantiacus Strain MH191 Shows Media-Based Dependency for the Production of Bioactive Compounds with Potential Antifungal Activity.

Streptomyces species can form beneficial relationships with hosts as endophytes, including the phytopathogen-inhibiting strain, Streptomyces griseoaurantiacusMH191, isolated from wheat plants. Using genomic characterization and untargeted metabolomics, we explored the capacity of strain MH191 to inhibit a range of fungal phytopathogens through the production of secondary metabolites. Complete genome assembly of strain MH191 predicted 24 biosynthetic gene clusters. Secondary metabolite production was assessed following culture on six different media, with the detection of 205 putative compounds. Members of the manumycin family, undecylprodigiosin, and desferrioxamine were identified as the predominant metabolites. Antifungal activity was validated for undecylprodigiosin and manumycin. These compounds were produced from different BGCs, which showed similarity to asukamycin, undecylprodigiosin, and FW0622 gene clusters, respectively. The growth of strain MH191 on different media illustrated the metabolic regulation of these gene clusters and the strain's extended chemical potential, with the asukamycin gene cluster alone, producing a variety of antifungal metabolites. The study highlights the extended chemical capability of strain MH191, which could be exploited as a biological control agent for designing future crop protection solutions.

Multiplex antimicrobial activities of the self-assembled amphiphilic polypeptide β nanofiber KF-5 against vaginal pathogens

BackgroundVaginal infections caused by multidrug-resistant pathogens such as Candida albicans and Gardnerella spp. represent a significant health challenge. Current treatments often fail because of resistance and toxicity. This study aimed to synthesize and characterize a novel amphiphilic polypeptide, KF-5, and evaluate its antibacterial and antifungal activities, biocompatibility, and potential mechanisms of action.ResultsThe KF-5 peptide was synthesized via solid-phase peptide synthesis and self-assembled into nanostructures with filamentous and hydrogel-like configurations. Characterization by scanning electron microscopy (SEM), transmission electron microscopy (TEM), and atomic force microscopy (AFM) confirmed the unique nanostructural properties of KF-5. KF-5 (125, 250, or 500 µg/ml) demonstrated potent antibacterial and antifungal activities, with significant inhibitory effects on drug-resistant Candida albicans and Gardnerella spp. (P < 0.05). In vitro assays revealed that 500 µg/ml KF-5 disrupted microbial cell membranes, increased membrane permeability, and induced lipid oxidation, leading to cell death (P < 0.05). Cytotoxicity tests revealed minimal toxicity in human vaginal epithelial cells, keratinocytes, and macrophages, with over 95% viability at high concentrations. Molecular dynamics simulations indicated that KF-5 interacts with phospholipid bilayers through electrostatic interactions, causing membrane disruption. In vivo studies using a mouse model of vaginal infection revealed that 0.5, 1, and 2 mg/ml KF-5 significantly reduced fungal burden and inflammation, and histological analysis confirmed the restoration of vaginal mucosal integrity (P < 0.01). Compared with conventional antifungal treatments such as miconazole, KF-5 exhibited superior efficacy (P < 0.01).ConclusionsKF-5 demonstrates significant potential as a safe and effective antimicrobial agent for treating vaginal infections. Its ability to disrupt microbial membranes while maintaining biocompatibility with human cells highlights its potential for clinical application. These findings provide a foundation for further development of KF-5 as a therapeutic option for combating drug-resistant infections.

Systematic discovery of antibacterial and antifungal bacterial toxins.

Microorganisms use toxins to kill competing microorganisms or eukaryotic cells. Polymorphic toxins are proteins that encode carboxy-terminal toxin domains. Here we developed a computational approach to identify previously undiscovered, conserved toxin domains of polymorphic toxins within 105,438 microbial genomes. We validated nine short toxins, showing that they cause cell death upon heterologous expression in either Escherichia coli or Saccharomyces cerevisiae. Five cognate immunity genes that neutralize the toxins were also discovered. The toxins are encoded by 2.2% of sequenced bacteria. A subset of the toxins exhibited potent antifungal activity against various pathogenic fungi but not against two invertebrate model organisms or macrophages. Experimental validation suggested that these toxins probably target the cell membrane or DNA or inhibit cell division. Further characterization and structural analysis of two toxin-immunity protein complexes confirmed DNase activity. These findings expand our knowledge of microbial toxins involved in inter-microbial competition that may have the potential for clinical and biotechnological applications.

Isofunctional but Structurally Different Methyltransferases for Dithiolopyrrolone Diversification.

Dithiolopyrrolone (DTP) natural products are produced by several different bacteria and have potent antibacterial, antifungal and anticancer activities. While the amide of their DTP core can be methylated to fine-tune bioactivity, the enzyme responsible for the amide N-methylation has remained elusive in most taxa. Here, we identified the amide methyltransferase XrdM that is responsible for xenorhabdin (XRD) methylation in Xenorhabdus doucetiae but encoded outside of the XRD gene cluster. XrdM turned out to be isofunctional with the recently reported methyltransferase DtpM, that is involved in the biosynthesis of the DTP thiolutin, although its X-ray structure is unrelated to that of DtpM. To investigate the structural basis for ligand binding in both enzymes, we used X-ray crystallography, modeling, site-directed mutagenesis, and kinetic activity assays. Our study expands the limited knowledge of post-non-ribosomal peptide synthetase (NRPS) amide methylation in DTP biosynthesis and reveals an example of convergent evolution of two structurally completely different enzymes for the same reaction in different organisms.

Understanding the biosynthesis, metabolic regulation, and anti-phytopathogen activity of 3,7-dihydroxytropolone in Pseudomonas spp.

The genus Pseudomonas is a prolific source of specialized metabolites with significant biological activities, including siderophores, antibiotics, and plant hormones. These molecules play pivotal roles in environmental interactions, influencing pathogenicity, inhibiting microorganisms, responding to nutrient limitation and abiotic challenges, and regulating plant growth. These properties mean that pseudomonads are suitable candidates as biological control agents against plant pathogens. Multiple transposon-based screens have identified a Pseudomonas biosynthetic gene cluster (BGC) associated with potent antibacterial and antifungal activities, which produces 7-hydroxytropolone (7-HT). In this study, we show that this BGC also makes 3,7-dihydroxytropolone (3,7-dHT), which has strong antimicrobial activity toward Streptomyces scabies, a potato pathogen. Through metabolomics and reporter assays, we unveil the involvement of cluster-situated genes in generating phenylacetyl-coenzyme A, a key precursor for tropolone biosynthesis via the phenylacetic acid catabolon. The clustering of these phenylacetic acid genes within tropolone BGCs is unusual in other Gram-negative bacteria. Our findings support the interception of phenylacetic acid catabolism via an enoyl-CoA dehydratase encoded in the BGC, as well as highlighting an essential role for a conserved thioesterase in biosynthesis. Biochemical assays were used to show that this thioesterase functions after a dehydrogenation-epoxidation step catalyzed by a flavoprotein. We use this information to identify diverse uncharacterized BGCs that encode proteins with homology to flavoproteins and thioesterases involved in tropolone biosynthesis. This study provides insights into tropolone biosynthesis in Pseudomonas, laying the foundation for further investigations into the ecological role of tropolone production.IMPORTANCEPseudomonas bacteria produce various potent chemicals that influence interactions in nature, such as metal-binding molecules, antibiotics, or plant hormones. This ability to synthesize bioactive molecules means that Pseudomonas bacteria may be useful as biological control agents to protect plants from agricultural pathogens, as well as a source of antibiotic candidates. We have identified a plant-associated Pseudomonas strain that can produce 3,7-dihydroxytropolone, which has broad biological activity and can inhibit the growth of Streptomyces scabies, a bacterium that causes potato scab. Following the identification of this molecule, we used a combination of genetic, chemical, and biochemical experiments to identify key steps in the production of tropolones in Pseudomonas species. Understanding this biosynthetic process led to the discovery of an array of diverse pathways that we predict will produce new tropolone-like molecules. This work should also help us shed light on the natural function of antibiotics in nature.

Valorization of oil refinery by-products: production of sophorolipids utilizing fatty acid distillates and their potential antibacterial, anti-biofilm, and antifungal activities.

Starmerella bombicola is a native yeast strain producing sophorolipids as secondary metabolites. This study explores the production, characterization, and biological activities of sophorolipids and investigates the antimicrobial, anti-biofilm, and antifungal properties of sophorolipids produced from oil refinery wastes by the yeast Starmerella bombicola. The present work demonstrated that S. bombicola MTCC 1910 when grown in oil refinery wastes namely palm fatty acid distillates and soy fatty acid distillates enhanced the rate of sophorolipids production drastically in comparison to vegetable oil, sunflower oil used as hydrophobic feedstock. Sophorolipid yields were 18.14, 37.21, and 46.1g/L with sunflower oil, palm, and soy fatty acid distillates respectively. The crude biosurfactants were characterized using TLC, FTIR, and HPLC revealing to be acetylated sophorolipids containing both the acidic and lactonic isomeric forms. The surface lowering and emulsifying properties of the sophorolipids from refinery wastes were significantly higher than the sunflower oil-derived sophorolipids. Also, all the sophorolipids exhibited strong antibacterial properties (minimum inhibitory concentrations were between 50 and 200µgmL-1) against Salmonella typhimurium, Bacillus cereus, and Staphylococcus epidermidis and were validated with morphological analysis by Scanning electron microscopy. All the sophorolipids were potent biofilm inhibitors and eradicators (minimum biofilm inhibitory and eradication concentrations were between12.5to1000µgmL-1) for all the tested organisms. Furthermore, antifungal activities were also found to exhibit about 16-56% inhibition at 1mgmL-1 for fungal mycelial growth. Therefore, this endeavour of sophorolipids production using palm and soy fatty acid distillates not only opens up a window for the bioconversion of industrial wastes into productive biosurfactants but also concludes that sophorolipids from oil refinery wastes are potent antimicrobial, anti-biofilm, and antifungal agents, highlighting their potential in biotechnological and medical applications.

Alkaloids solenopsins from fire ants display in vitro and in vivo activity against the yeast Candida auris

ABSTRACT The urgency surrounding Candida auris as a public health threat is highlighted by both the Center for Disease Control (CDC) and World Health Organization (WHO) that categorized this species as a priority fungal pathogen. Given the current limitations of antifungal therapy for C. auris, particularly due to its multiple resistance to the current antifungals, the identification of new drugs is of paramount importance. Some alkaloids abundant in the venom of the red invasive fire ant (Solenopsis invicta), known as solenopsins, have garnered attention as potent inhibitors of bacterial biofilms, and there are no studies demonstrating such effects against fungal pathogens. Thus, we herein investigated the antibiotic efficacy of solenopsin alkaloids against C. auris biofilms and planktonic cells. Both natural and synthetic solenopsins inhibited the growth of C. auris strains from different clades, including fluconazole and amphotericin B-resistant isolates. Such alkaloids also inhibited matrix deposition and altered cellular metabolic activity of C. auris in biofilm conditions. Mechanistically, the alkaloids compromised membrane integrity as measured by propidium iodide uptake in exposed planktonic cells. Additionally, combining the alkaloids with AMB yielded an additive antifungal effect, even against AMB-resistant strains. Finally, both extracted solenopsins and the synthetic analogues demonstrated protective effect in vivo against C. auris infection in the invertebrate model Galleria mellonella. These findings underscore the potent antifungal activities of solenopsins against C. auris and suggest their inclusion in future drug development. Furthermore, exploring derivatives of solenopsins could reveal novel compounds with therapeutic promise.

Biogenic synthesis and characterization of antimicrobial, antioxidant, and antihemolytic zinc oxide nanoparticles from Desertifilum sp. TN-15 cell extract

Cyanobacteria, being a prominent category of phototrophic organism, exhibit substantial potential as a valuable source of bioactive compounds and phytonutrients, including liposomes, amino derivatives, proteins, and carotenoids. In this investigation, a polyphasic approach was employed to isolate and characterize a newly discovered cyanobacterial strain from a rice field in the Garh Moor district of Jhang. Desertifilum sp. TN-15, a unique and less explored cyanobacterial strain, holds significant promise as a novel candidate for the synthesis of nanoparticles. This noticeable research gap underscores the novelty and untapped potential of Desertifilum sp. TN-15 in the field of nanomedicine. The characterization of the biogenically synthesized ZnO–NPs involved the application of diverse analytical techniques. Ultraviolet–visible spectroscopy revealed a surface plasmon resonance peak at 298 nm. Fourier transform infrared spectral analysis was utilized to confirm the involvement of biomolecules in the biogenic synthesis and stability. Scanning electron microscopy was employed to probe the surface morphology of the biogenic ZnO–NPs unveiling their size of 94.80 nm and star-shaped. Furthermore, X-ray diffraction analysis substantiated the crystalline nature of ZnO–NPs, with a crystalline size measuring 46 nm. To assess the physical stability of ZnO–NPs, zeta potential and dynamic light scattering measurements were conducted, yielding values of + 31.6 mV, and 94.80 nm, respectively, indicative of favorable stability. The antibacterial capabilities of Desertifilum sp. TN-15 are attributed to its abundance of bioactive components, including proteins, liposomes, amino derivatives, and carotenoids. Through the synthesis of zinc oxide nanoparticles (ZnO–NPs) with this strain, we have effectively used these chemicals to generate nanoparticles that exhibit noteworthy antibacterial activity against Staphylococcus aureus (MIC: 30.05 ± 0.003 µg/ml). Additionally, the ZnO–NPs displayed potent antifungal activity and antioxidant properties, as well as significant antihemolytic effects on red blood cells (IC50: 4.8 µg/ml). Cytotoxicity assessment using brine shrimps revealed an IC50 value of 3.1 µg/ml. The multifaceted actions of the biogenically synthesized ZnO–NPs underscore their potential applications in pharmacological and therapeutic fields. This study proposes a novel method for ZnO–NPs production utilizing the recently identified cyanobacterial strain Desertifilum sp. TN-15, highlighting the growing significance of biological systems in the environmentally friendly fabrication of metallic oxide nanomaterials.

Synthesis, characterization, antiproliferative, antibacterial activity, RDG, ELF, LOL Molecular docking and physico chemical properties of novel benzodiazepine derivatives

Four new benzodiazepine derivatives of 2-(2-(ethyl(methyl)amino)benzo [b][1,4]thiazepin-4-yl)phenol (EMBT), (2-(4-ethylbenzo[b][1,4]thiazepin-2-yl)phenol (EBT), 2-(7-chloro-2-(ethyl(methyl)amino)benzo[b][1,4]thiazepin-4-yl)phenol (CEMBT) and 2-(7-chloro-4-ethylbenzo[b][1,4]thiazepin-2-yl)phenol) (CEBT) has been synthesized. The synthesized compounds were characterized by NMR, FT-IR, UV-Vis and ESI-mass spectrometric techniques. The synthesized compounds were evaluated the cytotoxic assay in vitro antiproliferative activity against MCF-7 and HepG2 cancer cells. Further, antibacterial and antifungal screening were used to investigate the biological profile of 1,4-benzodiazepine derivatives. Antibacterial and antifungal activities were carried out, with potent antifungal activity against a few species. The structural, electronic, and vibrational properties of EMBT, EBT, CEMBT, and CEBT have been examined computationally using the hybrid B3LYP method and the 6-311++G(d,p) basis set basis set. Furthermore, molecular docking was used to study the binding interactions of the synthesized compounds and the standard drug Tamoxifen with the hERalpha LBD target protein.

Synthesis, Antimicrobial - Cytotoxic Evaluation, and Molecular Docking Studies of Quinolin-2-one Hydrazones Containing Nitrophenyl or Isonicotinoyl/Nicotinoyl Moiety.

By applying the hybrid molecular strategy, in this study, we reported the synthesis of fifteen quinolin-2-one hydrazones containing nitrophenyl or nicotinonyl/isonicotinoyl moiety, followed by in vitro and in silico evaluations of their potential antimicrobial and anticancer activities. In vitro antimicrobial evaluation of the target compounds on seven pathogenic strains, applying the broth microdilution method, revealed that compound 4a demonstrated the most potential antifungal activity against C. albicans (MIC 512 μg mL-1) and C. krusei (MIC 128 μg mL-1). In vitro cytotoxic evaluation of the target compounds on three human cancer cell lines, employing the MTT method, suggested that compound 5c exhibited the most potential cytotoxicities against HepG2 (IC50 10.19 μM), A549 (IC50 20.43 μM), and MDA-MB-231 (IC50 16.82 μM) cells. Additionally, molecular docking studies were performed to investigate the binding characteristics of compounds 4a and 5c with fungal lanosterol 14α-demethylase and human topoisomerase I-II, respectively, thereby contributing to the elucidation of their in vitro antifungal and cytotoxic properties. Furthermore, compounds 4a and 5c, via SwissADME prediction, could exhibit favorable physicochemical and pharmacokinetic properties. In conclusion, this study provides valuable insights into the potential of quinolin-2-one hydrazones as promising candidates for the development of novel antimicrobial and anticancer agents in the future.

An in-depth exploration of ethnomedicinal applications, phytochemical profiles, and pharmacological potentials: unveiling Withania somnifera

Researchers have extensively studied Withania somnifera (L.) Dunal, a woody shrub renowned for its multifaceted medicinal attributes such as antibacterial, anti-inflammatory, adaptogenic, aphrodisiac, and tonifying properties, because of its medicinal and traditional values. However, comprehensive information about its medicinal uses and pharmacological implications is scattered across various sources. Thus, this study aims to provide a comprehensive review of its ethnomedicinal uses, phytochemistry, and pharmacological attributes, consolidating information from diverse data sources. Systematic investigations have revealed the presence of diverse phytochemicals in W. somnifera, including major alkaloids, withanolides, flavonoids, tannins, oils, phytosterols, and amino acids. Extracts, fractions, and bioactive compounds derived from W. somnifera exhibited potent antibacterial, anti-inflammatory, anti-aging, anti-analgesic, anti-cancer, antivenom, anti-fungal, and anti-viral activities. W. somnifera serves as a valuable source of phytochemicals with diverse biological activities, offering significant therapeutic benefits globally. However, further studies are needed to assess potential side effects. Additionally, while several isolated compounds have demonstrated notable bioactivities, future research should focus on elucidating their mechanistic features to facilitate their integration into drug discovery endeavors.

Comparison of piperine content, antimicrobial and antioxidant activity of Piper chaba root and stem

Piper chaba (locally known as “Choi Jhal”) is used traditionally as spices and folk medicine in different parts of Bangladesh. One of the most important bioactive compounds in this plant is piperine. In this study, the amount of piperine in P. chaba root and stem was investigated and the optimal solvent for piperine extraction at room temperature was also studied. High performance liquid chromatography (HPLC) was operated using a reverse phase column where methanol and water (70:30) were used as mobile phase. The detection was performed using photo diode array (PID) detector at a wavelength of 345 nm. The standard piperine showed linearity between 0.005 % and 0.04 % and the correlation co-efficient found for the linearity was 0.9933. The percentage of relative standard deviation (RSD) for both retention time and peak area were less than 2.0 %. The theoretical plate number (N) > 3000 and a tailing factor (T) < 1.5 were found in the acceptable range. The recovery percentage (%) of standard piperine was 99.16 %. Low value of co-efficient of variation and standard deviation are recognized for high precision of the method. The highest amount of piperine was found in root extracted with methanol (MR) amounting to 1.75 % in the root powder. The maximum amount of piperine in the stem was 1.59 % when extracted with methanol (MS). The piperine quantification in other extract like n-hexane root (HR), ethyl acetate root (ER), n-hexane stem (HS), ethyl acetate stem (ES) were 0.76 %, 1.69 %, 0.33 % and 1.46 % respectively. Methanol has given the highest yield of piperine compared to ethyl acetate and n-hexane for both root and stem. The developed method was simple, rapid, economic and validated in terms precision, accuracy and recovery. This selective method is found to be repeatable, accurate and successfully utilized for the Piper extract in marketed and pharmaceutical samples with well chromatographic conditions. The ethyl acetate extract of root and stem showed promising DPPH (1, 1-diphenyl-2-picrylhydrazyl) free radical scavenging activity with an IC50 value of 39.62 ± 0.95 μg/mL and 43.85 ± 1.50 μg/mL respectively. The study reports potential antibacterial activity and antifungal activity of P. chaba root and stem extracts. These outcomes revealed that different extracts of P. chaba may be used as natural preservatives.

Eco‐friendly Green Synthesis of Silver Nanoparticles Using Daphne Mucronata Royle Seeds Extract and the Potential Antibacterial, Antifungal, and Scolicidal Activities

AbstractGreen synthesized silver nanoparticles (AgNPs) have received lots of attention due to being used as potential therapeutic agents. For the first time, this research investigated the biosynthesis of silver nanoparticles using the extract of Daphne mucronata seeds, which are rich in phenolic and polyphenolic substances and evaluated their antibacterial, antifungal, and scavenging activities. The process of nanoparticle (NPs) preparation was confirmed using UV–vis spectroscopy with an absorption peak at a wavelength of 440 nm. Dynamic light scattering (DLS) was used to determine the particles' distribution. Fourier‐transform infrared spectroscopy (FTIR) validated the functional groups contributing to the reduction of Ag+ to Ag. Moreover, X‐ray diffraction analysis (XRD), scanning electron microscopy (SEM), and transmission electron microscopy (TEM) approved the crystalline nature and spherical shape of the particles with mean and standard deviation of particle size to be 60.25 and 24.88 nm, respectively. The antibacterial, antifungal, and scolicidal activities of AgNPs were studied using disc diffusion against four standard bacteria species and microdilution methods for four Candida strains. The greatest effect of AgNPs with the highest concentration (80 µg/mL) was observed on Staphylococcus aureus (22.26 mm) and the lowest on Pseudomonas aeruginosa (19.07 mm). In the case of Candida fungus, the highest effect of AgNPs was reported for Candida krusei (7.93 µg/mL) and the lowest for Candida albicans (63.49 µg/mL). Also, these nanoparticles were able to register 100% lethality on the Echinococcus granulosus parasite in 15 min at a concentration (80 µg/mL). Therefore, the production of AgNPs as a renewable and cheap material can be effective after performing all the necessary tests as antibacterial, antifungal and antiparasitic agents with the least side effects in biomedical and pharmaceutical sciences.

Comparative analysis of antifungal properties in medicinal plant extracts for sustainable agriculture

The escalating environmental repercussions of pesticide use in pest and disease management underscore the urgency for alternative strategies. One promising avenue involves harnessing natural antifungal properties present in plant extracts. This study aimed to assess the antifungal efficacy of aqueous and ethanolic extracts from five medicinal plants, viz., C. sativa L., S. moorcraftiana L., S. nigrum L., F. vesca L., and R. pseudoacacia, which were screened for their antifungal activity against various soil-borne fungi, viz., A. niger, A. flavus, A. terreus, R. stolonifer, M. mucedo, F. oxysporum, A. alternata, P. notatum, C. cladosporioides, and C. lunata. Phytochemical analysis exhibited the presence of phenols, alkaloids, tannins, flavonoids, quinines, and terpenoids. Results revealed potent antifungal activity across all tested fungi, significantly inhibiting mycelial growth compared to control. S. nigrum and C. sativa extracts exhibited the highest efficacy against multiple fungal pathogens. The inhibition in mycelial growth in ethanolic and aqueous plant extracts of C. sativa against A. niger varies between 3.00 mm to 6.00 mm and 4.00 mm–6.33 mm, against A. flavus 3.33 mm–11.66 mm and 4 mm–12.66 mm, A. terreus (3.00 mm–6.00 mm and 3.66 mm–7.00 mm), R. stolonifer (3.00 mm–5.33 and 3.66 mm–6.33 mm), M. mucedo (8.33 mm–17.66 mm and 9.66 mm–18.66 mm), F. oxysporum (6.66 mm–12.33 mm and 7.33 mm–13.33 mm), A. alternata (4.66 mm–11.33 mm and 5.33 mm–14.00 mm), P. notatum (9.33 mm–23.00 mm and 9.66 mm–24.33 mm), C. cladosporioides (4.33 mm–8.66 mm and 5.33 mm–9.66 mm), and C. lunata (14.00 mm–20.33 mm and 17.00 mm–21.33 mm) in different concentrations of plant extracts respectively. Likewise, the inhibition in mycelial growth in ethanolic and aqueous plant extracts of S. nigrum against A. niger at different concentrations varies between 8.00 mm to 17.66 mm and 9.00 mm–18.66 mm, A. flavus (8.33 mm–12.66 mm and 9 mm–14 mm), A. terreus (2.33 mm–5.66mm and 3 mm–7 mm), R. stolonifer (13.33 mm–20.33 mm and 17.66 mm–24.66 mm), M. mucedo (10.66 mm–12.00 mm and 11.66 mm–13.00 mm), F. oxysporum (15.66 mm–22.33 and 18.00 mm–24.00 mm), A. alternata (10.66 mm–13.00 mm and 11.66 mm–14.00 mm), P. notatum (5.33 mm–13.33 mm and 6.33 mm–18.66 mm, C. cladosporioides (3.33 mm–7.66 mm and 4.00 mm–8.00 mm), and C. lunata (3.66 mm–6.33 mm and 4.66 mm–6.66 mm), respectively. These findings suggest that these plant extracts have the potential to be natural fungicides, providing promising alternatives for disease management in agriculture.

In vitro and silico activity of piperlongumine against azole-susceptible/resistant Aspergillus fumigatus and terbinafine-susceptible/resistant Trichophyton species

In recent years, the widespread emergence of drug resistance in yeasts and filamentous fungi to existing antifungal armamentariums has become a severe threat to global health. There is also concern regarding increased rates of azole resistance in Aspergillus fumigatus and Terbinafine resistance in Trichophyton species. To overcome this concern of resistance to regular therapies, new antifungal drugs with novel and effective mechanisms are crucially needed. Herbal remedies may be promising strategies for the treatment of resistant infections. We aimed to investigate the in vitro and silico activity of piperlongumine against clinical azole susceptible/resistant A. fumigatus and terbinafine-susceptible/resistant Trichophyton species. In the current study, piperlongumine demonstrated potent antifungal activity, with minimum inhibitory concentrations (MICs) ranging from 0.016-4 μg/mL against Trichophyton isolates and 0.25-2 μg/mL for A. fumigatus isolates. Additionally, molecular docking studies indicated that piperlongumine has a strong binding affinity to the active sites of squalene epoxidase and sterol 14-alpha demethylase. However, further studies are warranted to correlate these findings with clinical outcomes and provide the basis for further investigations to pave the way for developing novel antifungal agents.

Antifungal Activity of Pseudomonas chlororaphis 1S4

The potential of Pseudomonas chlororaphis 1S4 strain as an antifungal biocontrol agent against three species of the economically important Fusarium pathogens: Fusarium proliferatum C1, Fusarium oxysporum F6, and Fusarium solani F7 is studied. P. chlororaphis 1S4 24 and 48 h fresh and sterilized broth cultures were used to assess their antifungal properties for 168 hours. P. chlororaphis 1S4 imposed fungal growth inhibition of 64-85% against all fungal species, best presented at a relatively early stage of the fungi development (72 h) and sustained throughout the whole cultivation period. The sterilized broth bacterial cultures maintained about 60% - 100% of the fresh culture potential to retard the fungal growth. P. chlor¬oraphis 1S4 ability to produce exocellular phenazine-1-carboxylic acid and siderophores was determined. Their antifungal effect was checked after a high-temperature treatment. The potent antifungal activity of the P. chlororaphis 1S4 strain is speculated to be related to the biosynthesis of these biologically active substances that serve as effective bio-fungicides. Thus, the P. chlororaphis 1S4 antifungal potential could be utilized in agricultural initiatives focused on biocontrol.

Design, Synthesis, and Antifungal Evaluation of Novel Pyrazole-5-sulfonamide Derivatives for Plant Protection.

To develop further novel environmentally friendly antifungal agents with high efficacy, a series of pyrazole-5-sulfonamide derivatives were designed and synthesized by using the active molecules synthesized in previous works as lead compounds. Their antifungal activities were evaluated in vitro against ten highly destructive plant pathogenic fungi. The bioassay results indicated that more than half of the target compounds displayed potent antifungal activities (inhibition rate ≥85%) against Valsa mali and Sclerotinia sclerotiorum at 20 mg/L. Among them, compound C22 exhibited significant broad-spectrum antifungal activities against V. mali, S. sclerotiorum, Rhizoctonia solani, Botrytis cinerea, and Trichoderma viride, with EC50 values of 0.45, 0.49, 3.06, 0.57, and 1.43 mg/L, respectively. Moreover, compounds C21 and C22 exhibited remarkable protective effects on apple Valsa canker similar to tebuconazole (89.5%) at 50 mg/L. Preliminary antifungal mechanism investigations demonstrated that compound C22 may have inhibited V. mali mycelial growth by inducing oxidative damage to the mycelium and compromising the integrity of the cell membrane. Meanwhile, compounds C21 and C22 exhibited no obvious toxicity to worker bees (Apis mellifera ligustica). Taken together, these pyrazole-5-sulfonamide derivatives, particularly compound C22, possess huge potential to be developed as novel environmentally friendly fungicides with high efficacy.

Antimicrobial mechanisms and antifungal activity of compounds generated by banana rhizosphere Pseudomonas aeruginosa Gxun-2 against fusarium oxysporum f. sp. cubense.

Fusarium wilt of banana, also recognized as Panama disease, is caused by the soil-borne fungus Fusarium oxysporum f. sp. cubense tropical race 4 (FOC TR4). In recent years, strategies utilizing biocontrol agents, comprising antifungal microorganisms and their associated bioactive compounds from various environments, have been implemented to control this destructive disease. Our previous study showed that Pseudomonas aeruginosa Gxun-2 had significant antifungal effects against FOC TR4. However, there has been little scientific investigation of the antibacterial or antifungal activity. The aim of this study was to isolate, identify and evaluate the inhibition strength of active compounds in P. aeruginosa Gxun-2, so as to explain the mechanism of the strain inhibition on FOC TR4 from the perspective of compounds. The main antibacterial compounds of strain Gxun-2 were isolated, purified and identified using by fermentation extraction, silica gel column chromatography, thin-layer chromatography (TLC), high-performance liquid chromatography (HPLC), and nuclear magnetic resonance (NMR) techniques. The effect of the compounds on the mycelial growth, morphology and spore germination of strain FOC TR4 was observed by 96-well plate method and AGAR diffusion method. Among the metabolites produced by the strain, four antifungal compounds which were identified phenazine (C12H8N2), phenazine-1-carboxylic acid (PCA) (C13H8N2O2), 2-acetamidophenol (C8H9NO2) and aeruginaldehyde (C10H7NO2S) were identified through HPLC and NMR. Of these compounds, phenazine and PCA exhibited the most pronounced inhibitory effects on the spore germination and mycelial growth of FOC TR4. Phenazine demonstrated potent antifungal activity against FOC TR4 with a minimum inhibitory concentration (MIC) of 6.25 mg/L. The half-maximal effective concentration (EC50) was calculated to be 26.24 mg/L using the toxicity regression equation. PCA exhibited antifungal activity against FOC TR4 with an MIC of 25 mg/L and an EC50 of 89.63 mg/L. Furthermore, phenazine and PCA triggered substantial morphological transformations in the mycelia of FOC TR4, encompassing folding, bending, fracturing, and diminished spore formation. These findings indicate that strain Gxun-2 plays a crucial role in controlling FOC TR4 pathogenesis, predominantly through producing the antifungal compounds phenazine and PCA, and possesses potential as a cost-efficient and sustainable biocontrol agent against Fusarium wilt of banana in forthcoming times.

Exploring the antifungal properties of neem (Azadirachta indica) during: A comprehensive review (2010-2020)

Neem (Azadirachta indica) is a versatile medicinal plant with a long history of use in traditional medicine systems. Among its various therapeutic properties, neem has gained attention for its potent antifungal activity. This paper provides a comprehensive review of the antifungal properties of neem, highlighting its mechanisms of action, efficacy against fungal pathogens, and potential applications in clinical and agricultural settings. By synthesizing findings from a wide range of research studies, this review aims to deepen our understanding of neem's antifungal properties and explore its potential as a natural alternative for combating fungal infections.

Unveiling the therapeutic potential of Haloxylon articulatum extract: a comprehensive study on its phytochemical composition, antioxidant, antifungal, and antibacterial activities

ABSTRACT Haloxylon articulatum, commonly known as the salt tree have diverse medicinal benefits. The phytochemical content, antioxidant, antibacterial, and antifungal properties of the methanolic extract were assessed. The extract demonstrated a high concentration of flavonoids and phenolic components, with a Total Flavonoid Content (TFC) of 186 ± 3 µg QE/mg extract and a Total Phenolic Content (TPC) of 188.1 ± 0.4 µg GAE/mg extract. Bioactive substances with anti-inflammatory and antioxidant qualities, such as quercetin, rutin, chrysin, and caffeic acid, were detected by LC-MS analysis. Through IC50 values of 28.88, 14.13, and 23.03 µg/mL for DPPH, β-carotene, and ABTS tests, respectively, the extract demonstrated considerable antioxidant activity. Antibacterial activity was reported against Escherichia coli and Staphylococcus aureus, with bactericidal effects indicated by MIC and MBC values. The extract also exhibited potent antifungal activity against Thielaviopsis paradoxa and Alternaria sp. These results suggest that H. articulatum extract is a promising source of natural antioxidants and antimicrobial agents with potential therapeutic applications.