Excellent Antifungal Effects Research Articles

Multidimensional Optimization of R-LE001 for New Leads with Enhanced Antifungal Profiles.

Scaffold hopping and structural fine-tuning are important strategies for agrochemical innovation. Multidimensional optimization of the prevalidated antifungal lead R-LE001 was conducted via the design, synthesis, and bioevaluation of 53 new compounds differing in either scaffold or substituent. The antifungal structure-activity relationship (SAR) revealed that a number of amides containing 2-(2-oxazolinyl) aniline (NHPhOx) or 2-(2-thiazolinyl) aniline (NHPhthiOx) demonstrated a more promising antifungal effect than both R-LE001 and the positive control boscalid. Specifically, compound 10 (encoded LEX-K01) shows an excellent antifungal effect against Botrytis cinerea with an EC50 value lower than 0.11 μM. This small change leads to a significant improvement (over 1 order of magnitude) in bioactivity compared to that of either R-LE001 (EC50 = 1.41 μM) or boscalid (EC50 = 2.01 μM) and fluxapyroxad (EC50 = 4.35 μM). With much lower resistance factors, LEX-K01 (10) was more efficacious against the two boscalid-resistant strains of B. cinerea TZ01 and NJBH2017. A combination of LEX-K01 (10) and boscalid in a ratio of 1:3 showed synergistic effects against resistant B. cinerea TZ01 and NJBH2017, with SR values of 3.01 and 2.55, respectively. LEX-K01 (10) has a curative efficacy (70.3%) more prominent than that of boscalid (51.2%) in controlling disease caused by B. cinerea. The molecular docking simulation of LEX-K01 (10) with the SDH protein of B. cinerea displayed four hydrogen bonds with amino acid residues TYR144, ARG88, TRP81, and SER84, rationalizing a stronger affinity than boscalid. The scanning electron microscopy (SEM) characteristic revealed that it could cause an obvious collapse of B. cinerea mycelium. This work indicates that LEX-K01 (10) has the potential to be further explored as a new antifungal agent.

Palladium(II) complexes of thiobenzamide derivative ligands: Synthesis, crystal structure, supramolecular architecture, Hirshfeld surface analysis, and in vitro antibacterial and antifungal activities

Three thiobenzamide derivative ligands and their palladium complexes were synthesized. The synthesized compounds were characterized by several instrumental methods, such as 1H NMR, 13C NMR, and FT–IR. Additionally, the appropriate crystal of the [PdIICl2(L3H)2] complex was analyzed to determine the molecular structure. The single–crystal X–ray diffraction (SC–XRD) revealed that [PdIICl2(L3H)2] complex has a monoclinic crystal system, C2/c space group, a = 12.2969(11) Å, b = 18.7618(16) Å, c = 16.899(2) Å, β = 97.875(4)°. The intramolecular and intermolecular interactions in the crystal structure led to the formation of two synthon systems. In addition, a quantitative investigation of the noncovalent interactions in the structure was carried out through the utilization of Hirshfeld surface and 2D–fingerprint plot analyzes. Analysis of [PdIICl2(L3H)2] using 2D fingerprint analysis revealed a range of intermolecular interactions responsible for its stabilization. Among these interactions, intermolecular H···H (51.90%), Br···H/H···Br (16.00%), and Cl⋯H/H···Cl (10.40%) were found to be the most prominent types of interaction. The 3D layout of the crystal packing was evaluated during the energy framework computations, demonstrating that the electrostatic energy framework had a significant impact over the dispersion energy framework. Antibacterial and antifungal activities of the thiobenzamide derivative palladium complexes were also tested against Gram–positive (E. faecalis, S. aureus, B. subtilis, and S. pneumonia) and Gram–negative (P. aeruginosa and E. coli) bacterises and against fungi (C. glabrata and C. albicans). Palladium complexes exhibited to be more effective against fungi than against bacteria according to the MIC values. Particularly, [PdIICl2(L2H)]2 complex showed an excellent antifungal effect among the other palladium complexes, with low MIC values of 3.90 and 7.81 μg/mL against C. glabrata and C. albicans fungi, respectively.

Construction Strategy and Mechanism of a Novel Wood Preservative with Excellent Antifungal Effects.

Wood is a naturally porous material prone to microbial erosion and degradation in outdoor environments. Therefore, the development of an environmentally friendly wood preservative with excellent antibacterial effects and low toxicity is urgently needed. In this study, nitrogen-doped carbon quantum dots (N-CQDs) with excellent antifungal performance and fluorescent properties were synthesized using a one-step hydrothermal method with chitosan quaternary ammonium salt (HACC) as the raw material. The fluorescence characteristics of N-CQD preservatives can help track their position and distribution in wood. The minimum inhibitory concentration (MIC) of N-CQDs is 1.8 mg/mL, which was nearly 22 times lower than that of HACC (40.0 mg/mL) in the PDA medium. The decay resistance test demonstrated that wood treated with N-CQDs showed a considerably reduced decay degree and its mass loss rate decreased from 46 ± 0.5% to 3.8 ± 0.5%. Biological transmission electron microscopy revealed that N-CQDs effectively destroyed fungal cell structures, thereby hindering the growth of Coriolus versicolor. N-CQDs synthesized using the one-step hydrothermal method can be used as an efficient wood preservative that can effectively improve the utilization and service life of wood.

Preparation of AgNPs/oregano essential oil composite film and its antibacterial application in the conservation of paper relics

Electrospinning technology is an innovative method used to synthesize continuous ultra-fine polymer fibers of nanomaterials, offering a mild processing environment that enables the integration of bioactive substances, metal particles, and polymer matrix materials. Notably, silver nanoparticles (AgNPs) exhibit significant and eco-friendly antibacterial properties, as these small-sized metal nanoparticles can penetrate bacterial cells swiftly and induce quick sterilization. Additionally, oregano essential oil (OEO), extracted from natural plants, is an environmentally safe agent with broad-spectrum antibacterial and strong antioxidant properties. In this study, four types of electrospun membranes were prepared: polyacrylonitrile (PAN) nanofiber membranes, oregano essential oil (OEO) nanofiber membranes, silver nanofiber membranes loaded with oregano essential oil (AgNPs/OEO), silver nanofiber membranes (AgNPs). To characterize these membranes, their surface morphology, crystalline phase structures, and functional group characteristics were analyzed. The antibacterial effects of these four membranes on rice paper were then investigated through contact and non-contact experiments.Finally, AgNPs/OEO composite film exhibited excellent antifungal effects againstAspergillus nigeron rice paper under both conditions and was essentially non-invasive to the paper cultural relic’s ontology, offering a new method for the conservation of paper cultural relics.

Control of citrus blue and green molds by Actinomycin X2 and its possible antifungal mechanism

Citrus blue and green molds caused by Penicillium digitatum, P. italicum, and P. polonicum, are the major postharvest diseases of citrus fruit. In the present study, Actinomycin X2 (Act-X2), a naturally occurring antibiotic produced by Streptomyces species, was found to show excellent antifungal effect against these three pathogens with a minimum inhibitory concentration (MIC) value of 62.5 μg/mL for them all, which was better than the positive control thiophanate-methyl. Act-X2 significantly reduced the percentage of spore germination, and highly inhibited the mycelial growth of P. italicum, P. digitatum, and P. polonicum with EC50 values being 34.34, 13.76, and 37.48 μg/mL, respectively. In addition, Act-X2 greatly decreased the intracellular protein content while increasing the reactive oxygen species (ROS) level and superoxide anion (O2−) content in the mycelia of pathogens. In vivo test indicated that Act-X2 strongly inhibited the infection of navel oranges by these three Penicillium species, with an inhibition percentage of >50% for them all at the concentration of 10 MIC. Transcriptome analysis suggested that Act-X2 might highly influence the ribosomal functions of P. polonicum, which was supported as well by the molecular docking analysis of Act-X2 with some key functional proteins and RNAs of the ribosome. Furthermore, Act-X2 significantly reduced the decay percentage and improved the firmness, color, and sugar-acid ratio of navel oranges spray-inoculated with P. polonicum during the postharvest storage at 4 °C for 60 d.

Botanicals as a Source of Nanomaterial for Pest and Disease Management

Sustainable food production for a rapidly growing human population is one of the major challenges faced by the agriculture sector globally. Plant pests and pathogens cause significant reductions in crop production, with estimated global losses of 20-40% year-1, resulting in an increased use of environmentally toxic pesticides & fertilizers. The growing numbers of studies in nanotechnology are producing novel applications in many fields of science, especially in plant biotechnology and agriculture. Nanomaterials (NMs) have been used in breakdown of pollutants and reported worldwide for several different environmental applications. They play an important role in agriculture as nano-fertilizers and nano-pesticides, prepared by many methods such as physical, green synthesis or chemical synthesis methods. Green synthesis involves use of biological resources as microorganisms or plant extracts and doesn’t permit the use of any toxic chemicals, hence less bio-hazardous. Rate of reduction of metal ions using phytosynthesis has been observed to be much faster than microbial synthesis. Thus, it is considered as an accessible alternative for large scale production of nanomaterials, without use of chemicals. Phytosynthesized nanomaterials show excellent antibacterial effects, antifungal effects and anti-pest activity. Ocimum sanctum, Azadiracta indica, Paederia foetida, etc. had been successfully reported to be used in synthesis of many NMs of silver, gold, zinc, etc. Botanical nanomaterials offer considerable potential for increasing agricultural productivity and protection while reducing negative impacts on the environment and human health simultaneously.

Overcoming multidrug-resistant bacteria and fungi by green synthesis of AgNPs using Nepeta pogonosperma extract, optimization, characterization and evaluation of antibacterial and antifungal effects

This study explained a green synthesis of silver nanoparticles (AgNPs) using Nepeta pogonosperma extract and evaluated their antibacterial activity. Optimization of the temperature, concentration, pH, and reaction time was established to produce silver nanoparticles. The best condition was 10 mM AgNO3, pH = 14, temperature 85 °C, and reaction time 24 hours. The formation of silver nanoparticles was confirmed by colour-changing, UV-vis, FE-SEM, EDX, XRD, FT-IR, and DLS analysis. The prepared AgNPs had a spherical shape with an average size of 51.21±0.02 nm. In addition, our biofabricated nanoparticles displayed potential antibacterial activity against the tested strains. The MIC value of 1.17 µg/mL was determined against strains of Pseudomonas aeruginosa, Acinetobacter baumannii, and Escherichia coli and 2.34 µg/mL against Staphylococcus aureus, Klebsiella pneumoniae, Proteus mirabilis and Enterococcus faecalis. Furthermore, AgNPs exhibited excellent antifungal effects against Candida albicans strains (0.073 μg/mL). In general, N. pogonosperma played an important role in reducing Ag(+1) to Ag(0) and the production of Ag(0) with suitable surface features in combination with efficient biological activities.

Evaluation of eugenol‐derived monomers as antimicrobial agents in dental resin composites

AbstractThe aim of this study is to synthesize two eugenol‐derived halogenated monomers and to evaluate their properties as antibacterial and antifungal agents in the formulation of dental composite resins. The 4‐allyl‐2‐methoxyphenyl (2‐chloroethyl) carbonate (ECl) and 4‐allyl‐2‐methoxyphenyl 2,2,3,3,4,4,4‐heptafluorobutanoate (EF) monomers have halogens, chlorine or fluorine bonded in their structure, whose antibacterial activity is known. The characterization of ECl and EF monomers was made by Fourier transform infrared and 1H and 13C NMR. dental resin composites are formulated by mixing the BisGMA/TEGDMA, photoinitiator system, inorganic filler, and the ECl or EF monomer, respectively. The antimicrobial and antifungal activity of the experimental resins is determined using the strains of Staphylococcus aureus and Candida albicans. After copolymerization, DCRs with ECl or EF monomers significantly stop antibacterial growth and show excellent antifungal effect. The best results in the antibacterial test are using 0.5 or 3 wt% of the ECl monomer, while for the EF monomer is 5 wt%. On the other hand, the most adequate concentration of ECl and EF monomers in the antifungal activity is 0.5 wt%. The above demonstrates the ability of ECl and EF monomers to prevent antibacterial and antifungal growth in a dental composite resin, which would extend the useful life of a dental restoration.

Evaluation of antifungal activity of lactic acid bacteria against fungi in simulated cheese matrix

This study aimed to investigate the antagonist activity of lactic acid bacteria (LAB) isolated from Brazilian artisanal cheese and dairy environments against filamentous fungi commonly found in dairy products. In the in vitro test, a total of fifty-two LAB isolates were screened for their inhibitory effects against Aspergillus niger IOC 207 and Penicillium chrysogenum IOC 132. Among them, five strains (Weissella confusa W5, W8; Weissella paramesenteroides W9; Weissella cibaria W25; Lactiplantibacillus plantarum Q4C3) were selected for further in situ evaluation using a cheese matrix. The selected LAB strains exhibited excellent antifungal effect in simulated cheese matrix against both fungi targets; however, when combined with a commercial starter culture, their antifungal activity was reduced. Nevertheless, the results of this study suggest that these LAB strains may have potential as bioprotective cultures in food applications; they have the ability to produce antifungal compounds that could be characterized and potentially used as adjunct cultures in future food processing. Further research in this direction could shed light on their metabolic capabilities and pave the way for their potential use as biopreservatives in the food industry.

Facile preparation of fatty acids/nano [Al(OH)3/Al2O3]/wool fabric introducing thermal energy management with multifunctional properties

Development of facile fabrication of thermal energy storage for diverse purposes has become essential to improve energy efficiency. In this regard, for the first time, fatty acids/nano Al-based/wool composite was prepared by a simple one-step procedure through in situ formation. The treated fabric was characterized by FT-IR, Raman, XRD and SEM. DSC, TGA and thermal conductivity were conducted to investigate thermal behavior of the treated wool. The experimental results show the appropriate melting and solidifying temperature, 36.59 and 29.58 °C with responding enthalpies 59.22 and 52.08 J/g, respectively, for the desired application. TGA revealed the relatively improvement in thermal durability of the treated wool fabric. Embedding Al(OH)3/Al2O3 nanoparticles in eutectic phase change materials results in a 104.16 % increase in thermal conductivity. Despite the negative effect of fatty acids on flame retardant feature of the composite, aluminum hydroxide nanoparticles incorporated into the prepared composites imparted a good smoke suppression to the prepared composite. Moreover, the optimal sample illustrated excellent antibacterial and anti-fungal effects. The finished fabric also showed good activity for degradation of methylene blue under daylight irradiation. The treatment also greatly increased the water absorption of the composite and shrinkage resistance and also decreased alkali solubility. As a result, this thermos-regulative simple approach has a potentiality to be applied in various textile materials for diverse industries.

Effect and regulation of fatty acids on bacillomycin D synthesis.

Bacillomycin D is a cyclic antimicrobial lipopeptide that has excellent antifungal effects, but its application is limited due to its low yield. At present, it is not clear whether fatty acids regulate the synthesis of bacillomycin D. Therefore, the effects of nine fatty acids on the yield of bacillomycin D produced by Bacillus amyloliquefaciens fmbJ were studied. The results showed that sodium propionate, propionic acid, and butyric acid could increase the yield of bacillomycin D by 44, 40, and 10%, respectively. Reverse transcription polymerase chain reaction (RT-PCR) was used to detect the expression levels of bacillomycin D synthesis gene, signaling factors and genes related to fatty acid metabolism, so as to explore the mechanism of sodium propionate regulating bacillomycin D synthesis. In conclusion, sodium propionate could accelerate the tricarboxylic acid cycle and promoted spore formation, cell movement, the secretion of extracellular protease and the transcription of bacillomycin D synthesis gene by upregulating the expression of signal factors degU, degQ, sigH, sigM and spo0A and ultimately promoted the synthesis of bacillomycin D. In this study, the mechanism of sodium propionate increasing bacillomycin D production was explored from multiple perspectives, which provided theoretical support for the large-scale production of bacillomycin D and was expected to promote its wide application in food, agriculture and medicine fields.

Application of pH-responsive functionalized hollow mesoporous organosilica nanoparticles for wood preservation

Plant-derived preservatives exhibit excellent antifungal effects. However, their antifungal active ingredients can easily leach out. A properly designed functional response system can help realize the responsive release of preservatives and reduce leaching. Herein, the pH-responsive preservatives delivery system was designed and synthesized. The preservative (Forsythia) was encapsulated with hollow mesoporous organosilica nanoparticles (HMONs), and carbon quantum dots (CQDs) were employed as mesoporous plugging agents. Forsythia’s release was achieved by grafting pH-sensitive chemical bonds on the surface of the carrier. X-ray photoelectron spectroscopy and antifungal results showed that the pH-responsive switch was successfully broken. After 12 weeks of soil-jar incubation, the weight loss rate of treated wood was 2 % ± 0.5 %. The leaching of Forsythia–HMON–CQDs was lower than that of Forsythia under the same concentration. The design of the system reduced the leaching of Forsythia and extended the service life of wood. In addition, the system was also applicable to ammoniacal copper quat (ACQ). Forsythia–HMON–CQDs showed an outstanding fixation effect and antifungal ability, and its fluorescence can be used to track distribution in wood. This system can be extensively employed in protecting antifungal active ingredients and demonstrates an effective strategy for developing potential bio-based wood preservatives.

A novel cellulose nanocrystal-based antifungal aerogel for fluorometric detection and efficient removal of Cr(VI)

A novel multifunctional aerogel (MFA) was conveniently fabricated by cross-linking cellulose nanocrystals and polyethyleneimine capped-silver clusters for fluorometric sensing and efficient removal of Cr(VI). This novel MFA was characterized by TEM, XRD, and FT-IR, which show a high adsorption capacity for Cr (VI) (maximum at 589.68 mg/g). X-ray photoelectron spectroscopy confirmed that redox, electrostatic interaction, and chelation account for the high Cr(VI) adsorption. Moreover, MFA had excellent antifungal effects on fungi such as Aspergillus flavus and Aspergillus niger for as long as 10 days, prolonging its life cycle in the environment. More importantly, by using a smartphone, Cr(VI) concentrations over the range of 0–400 mg/L were effectively tested, with a limit of detection of 5 mg/L, providing the convenience for on-site detecting samples. This novel MFA shows promising potential for mass production and environmental treatment. • A multifunctional aerogel is made by cross-linking cellulose nanocrystals and polyethyleneimine capped-silver nanoclusters. • The aerogel shows fluorometric detection and efficient removal of Cr(VI) and strong antifungal effect. • The maximum adsorption capacity for Cr(VI) of this new aerogel is 589.68 mg/g. • Cr(VI) detection is simply implemented by using a smartphone with an application.

Antioxidant, Antibacterial, and Antifungal Activities of the Ethanolic Extract Obtained from Berberis vulgaris Roots and Leaves.

This work assessed the phenolic and flavonoid components and their antioxidant, antifungal, and antibacterial effects in the ethanolic extract of barberry leaf and roots. The antibactericidal activity of root and leaf extracts against pathogenic bacteria was tested using agar diffusion and microdilution broth production for the lowest inhibitory concentration (MIC). Berberis vulgaris root and leaf extracts inhibited Staphylococcus aureus ATCC9973, Escherichia coli HB101, Staphylococcus enteritis, and Escherichia coli Cip812. The disc assay technique was used to assess the bactericidal activity of the extracts versus both pathogenic Gram-positive and Gram-negative strains. Hydro alcoholic extract was more effective against bacterial than fungal strains. The results showed that Berberis vulgaris leaf and roots extract had similar antifungal activities. Berberis vulgaris root extract inhibited the mycelial growth of Penicillium verrucosum, Fusarium proliferatum, Aspergillus ochraceous, Aspergillus niger, and Aspergillus flavus. Berberis vulgaris root extract has excellent antioxidant, antibacterial, and antifungal effects. Berberis vulgaris exhibited antimicrobial activity in vitro, and MIC showed that Berberis vulgaris parts efficiently affected pathogens in vitro. In conclusion, both Berberis vulgaris roots and leaves have considerable antibacterial activity and can be used as a source of antibacterial, antioxidant, and bioactive compounds to benefit human health.

Amphotericin B and 5-flucytosine as fungicides against Penicillium italicum for citrus fruit rot

The expansion of the global population and improved living standards has created an increasing demand for fresh fruit. The combination of agricultural and medical development for new fungicides is one of the most effective approaches for keeping fruit fresh. Both amphotericin B and 5-flucytosine are quite safe and have a wide spectrum of antifungal activity. For the purpose of investigating their potential applications for preserving fruit freshness, we evaluated their antifungal efficiencies against Penicillium italicum in vitro and in vivo. The results showed that amphotericin B and 5-flucytosine significantly inhibited spore germination and the mycelial growth of P. italicum. The 5-flucytosine showed much better bioactivity than the well-known agricultural fungicide prochloraz, both in vitro and in vivo. Furthermore, crystal violet staining, propidium iodide dyeing, ultrastructural observation and the ergosterol content indicated that amphotericin B and 5-flucytosine destroyed the cellular ultrastructure and membrane integrity. In addition, nucleic acids (OD260) and proteins (OD280) escaped from P. italicum cells in a dose-dependent manner. The results of this study indicated that amphotericin B and 5-flucytosine have good potential as antifungal preservatives for postharvest citrus fruit due to their excellent antifungal effects, and that the primary mode of action was the destruction of the membrane integrity and permeability of P. italicum.

Discovery of evodiamine derivatives as potential lead antifungal agents for the treatment of superficial fungal infections

Mycosis, especially superficial fungal infections (SFIs), has been a serious threat to humans in recent years. Evodiamine (EVO), as an effective component of the Traditional Chinese Medicine Evodia rutaecarpa, has good antibacterial effects and low toxicity. In order to find out the potential therapeutic agents against SFIs, a series of EVO derivatives were synthesized and systematic evaluations of antifungal activity were carried out. Among them, compound A7 exhibited great antifungal activity with the values of MIC100 were 38, 38 and 2 μg/mL, respectively, against T. rubrum, T. mentagrophytes and C. albicans, and even stronger than that of ketoconazole (KCZ) with the values of MIC100 were 106, 106 and 3 μg/mL, respectively. Further antifungal evaluations in vitro verified that compound A7 indeed had favorable antifungal activity. Moreover, compound A7 could exert excellent antifungal effect on T. rubrum-infected guinea pigs, suggesting that A7 was an attractive molecule and could be a potential lead compound for the development of anti-fungal agents, and providing a great promising therapeutic strategy for fungal disease.

Drug-loaded mesoporous carbon with sustained drug release capacity and enhanced antifungal activity to treat fungal keratitis.

Fungal keratitis is a severe infectious corneal disease with a high rate of incidence and blindness. Since traditional treatments natamycin (NATA) eye drops, exhibit poor dissolution and bioavailability, and the efficacy of current therapeutic approaches remains limited. In this study, we innovatively utilized mesoporous carbon (Meso-C) and microporous carbon (Micro-C) as nanocarriers loaded with the antifungal drug NATA and silver nanoparticles (Ag-NPs). Porous carbon loaded with NATA and Ag-NPs has not previously been studied in fungal keratitis. Due to the mesoporous structure, high surface area and larger pore volume of Meso-C, it displayed greater superiority in sustained drug release and drug dispersity than Micro-C. Moreover, Meso-C could adsorb inflammatory cytokines during fungal infection. In vitro, Meso-C/NATA/Ag showed excellent antifungal effects. In vivo, compared with pure NATA treatment, Meso-C/NATA/Ag exhibited significantly improved therapeutic effects and reduced dosing frequency when treating fungal keratitis. Our study is the first to report the sustained drug release and improved drug dispersity of Meso-C/NATA and demonstrates that NATA and Ag-NPs-loaded Meso-C has therapeutic effects against fungal keratitis.

Trans-cinnamaldehyde inhibits Penicillium italicum by damaging mitochondria and inducing apoptosis mechanisms

Plant-derived essential oils have excellent antifungal effects and can be used for the preservation of fresh foods such as fruits and vegetables, but the detailed mechanism has not been fully elucidated. In this study, we investigated the inhibitory effects of trans-cinnamaldehyde on Penicillium italicum, a common pollution fungus in citrus, and explored the antifungal mechanism of trans-cinnamaldehyde by detecting fungal oxidative damage, mitochondrial metabolism, and cell apoptosis. These results showed that trans-cinnamaldehyde made the carboxylic acid cycle deregulated by altering the related enzyme activities (succinate dehydrogenase, malate dehydrogenase) and mid product. Moreover, the level of reactive oxygen species rose sharply while the redox level was out of regulation. The mitochondrial membrane potential collapsed, leading to the leakage of cytochrome c, and then triggering the activation of apoptotic protease, which was further confirmed by the significant increase in caspase-3 activity from (3.6 ± 0.6) U to (8.8 ± 1.1) U (P < 0.05). The cytochrome c in mitochondria was detected by confocal Raman microspectroscopy, the characteristic intensity index (I750/I2944) was decreased, indicating that the cytochrome c in mitochondria was reduced and leakage. Besides, the strong negative correlation between Raman intensity and the amount of cytochrome c leakage was established with the correlation coefficient of -0.9817. This study revealed that destroying the integrity of the mitochondrial membrane, activating the mitochondrial-mediated apoptosis pathway was the in-depth antifungal mechanism of trans-cinnamaldehyde; and Raman spectroscopy technology provided new ideas to study this process with high sensitivity determination of cytochrome c.

Amphotericin B Tamed by Salicylic Acid.

Although Amphotericin B (AmB) is considered as the “gold standard” treatment for deep fungal infections, owing to its excellent antifungal effect, it often causes severe hemolytic toxicity and nephrotoxicity, which limits its clinical use. We designed and synthesized AmB derivatives by attaching salicylic acid (SA) to the carboxyl group and confirmed their structures using 1H NMR, 13C NMR, HR-MS, and IR. We evaluated its biological activity in vitro and measured its ultraviolet–visible (UV–vis) absorption spectrum. The AmB-SA conjugates exhibited good antifungal effects against Candida albicans, Candida glabrata, and Cryptococcus neoformans compared with AmB, and the renal cytotoxicity toward HEK 293T cells in vitro was significantly reduced, with almost no nephrotoxicity in the therapeutic window of the drug. At the same time, the hemolytic toxicity was significantly reduced. Therefore, modification of AmB by introducing SA is an effective strategy to maintain the broad antifungal activity of AmB and reduce its cytotoxicity. These AmB derivatives could be applied in clinical therapy in the future.

Temperature-Responsive Pyraclostrobin-Loaded Octadecane Submicrocapsules with Lowered Toxicity.

Pyraclostrobin (Pyr) is one of the most effective fungicides. However, it can degrade via photolysis in water, it is toxic to aquatic life and if inhaled, it has a low solubility in water, that leads to difficulties when applying to plants by spraying. Additionally, the necessity of repeated (weekly) sprays of fungicides when the pathogen growth risk is the highest, such as at the temperature range of 24 to 36 °C and increased humidity of about 95%, leads to loss of efficiency of the fungicide and overdose of chemicals. In the present study, pyraclostrobin was microencapsulated to solve the abovementioned issues. As a core of capsules octadecane (OD) with a melting point of 28 °C was used, thus, the release of pyraclostrobin was controlled via temperature change. Pyraclostrobin-loaded submicrocapsules (PyrSMCs) were characterized using SEM, DLS, TGA/DSC, HPLC, FTIR methods; stimuli-responsivity was tested employing in vitro tests with pathogenic culture (Fungal strain of Pyrenophora teres - CPPF-453) grown in Petri dishes. Toxicity of PyrSMCs to Artemia salina was studied as well. Size of capsules was 200–600 nm along with the presence of bigger capsules with a diameter of 1–4 µm. PyrSMCs showed excellent antifungal effects above the melting point of octadecane. PyrSMCs demonstrated 29 times less toxicity than pyraclostrobin of technical grade. Overall, results show the potential of such capsules to be applied in the agricultural industry for precise agriculture strategies.