Search

Trimethyl lock (TML) systems have become increasingly important in medicinal and bioorganic chemistry, particularly for their roles in the targeted delivery of therapeutic agents and as integral components in fluorogenic probes for cellular imaging. The simplicity and efficiency of their synthesis have established TML systems as versatile platforms for the controlled release of active molecules under particular physiological conditions. This review consolidates recent advancements in the application of TML systems, with a focus on their use in drug delivery, cellular imaging, and other areas where precise molecular release is crucial. Additionally, we discuss the synthetic strategies employed to construct TML‐based conjugates, underscoring their potential to enhance the specificity and efficacy of bioactive compounds in various biomedical applications. [ABSTRACT FROM AUTHOR]

Mortalities due to mycoses have dramatically increased with the emergence of drug‐resistant strains and growing immune‐compromised populations globally. Azole antifungals have been the first choice against fungal infections of a wide spectrum and several azole derivatives with ester function were reported for their potentially promising and favorable activity against Candida spp. In this study, we designed and synthesized a series of 1‐(aryl)−2‐(1H‐imidazol‐1‐yl/1H‐1,2,4‐triazol‐1‐yl)ethyl esters, and tested them against seven reference Candida strains using EUCAST reference microdilution method. Among the series, 6a, 6d, and 6g proved highly potent in vitro compared to fluconazole; especially against Candida albicans and Candida tropicalis with minimum inhibitor concentration (MIC) values as low as 0.125 and 0.06 mg/L, respectively, although their activities against Candida krusei and Candida glabrata remained limited. The compounds also showed minimal toxicity to murine fibroblasts according to the in vitro cytotoxicity tests. Molecular modeling predicted 6g as an orally available druglike compound according to all parameters and CYP51 inhibition as the likely mechanism for their antifungal effects. The study underpins the promise of azoles with ester functionality as a potential scaffold for small‐molecule antifungal drug design. [ABSTRACT FROM AUTHOR]

Healthcare‐associated infections (HAI) are illnesses acquired during healthcare and are often the most important adverse event during healthcare. With the aim of increasing the effectiveness of disinfection/decontamination processes in the health service with safe and not promote microbial resistance, we propose the development of portable equipment associated with type C ultraviolet light (UVC). The efficiency of the irradiance emitted by the equipment (at dosages 3.5, 5.0, and 60 mJ/cm2) was determined by the action exerted after exposure against four different bacterial (Acinetobacter baumannii, Escherichia coli, Pseudomonas aeruginosa, and Staphylococcus aureus) and three different fungi (Candida albicans, C. parapsilosis, and Aspergillus section Fumigati). It was possible to observe that all treatments were capable of inactivating the bacterial species evaluated (p < 0.05), causing the irreversible death of these microorganisms. The most effective elimination of fungal agents was at a dose of 60 mJ/cm2 of UVC radiation, with a decrease in the fungal inoculum varying between 94% and 100% in relation to the control without exposure. Thus, our study showed that the application of the portable prototype with UVC light (254 nm) at a distance of 48 mm, allowed an average irradiance of 3.5 mW/cm2, with doses of 3.5 ≈ 60 mJ/cm2 (from 1 to 60 s of exposure), which can promote the total reduction of the bacteria evaluated and significantly reduce fungal growth. Therefore, this prototype could be used safely and effectively in the hospital environment, considerably reducing contamination and contributing to the reduction of healthcare‐associated infection risk. [ABSTRACT FROM AUTHOR]

Summary: A 3‐year‐old Quarter Horse gelding originating from Texas presented for fever and inappetence. An encapsulated, mixed echogenic cranial mediastinal mass visible ultrasonographically in the left and right fourth intercostal space that displaced the heart caudally was identified. Histological evaluation of needle biopsies obtained under general anaesthesia revealed a severe pyogranulomatous inflammatory process associated with intralesional round, 15–25 μm in diameter, thick double‐contoured cell wall fungal structures. Sequencing of products obtained from DNA extracted from the paraffin‐embedded biopsy sample and a panfungal PCR assay targeting the large ribosomal unit region had a 99.1% identity to either Coccidioides immitis or C. posadessii. Bronchoscopy revealed purulent exudate in the right primary bronchus. Cytological evaluation of bronchial alveolar lavage fluid (BALF) contained 96% moderately degenerative neutrophils and 4% macrophages. Fungal structures were not appreciated in the BALF. However, the mediastinitis could have resulted from inhalation and dissemination of arthroconidia through lymphatics or directly from the lung parenchyma. Quantitative immunodiffusion of serum for the presence of coccidioidal IgG antibodies yielded a titre of 1:256 suggestive of disseminated coccidioidomycosis. After oral fluconazole for 24 months, the horse's general health and athletic performance had returned to normal and the mediastinal mass was not appreciated sonographically. [ABSTRACT FROM AUTHOR]

Piperazine, a nitrogen‐containing heterocyclic compound, has potential in medical chemistry due to its versatile structure and ease of modification. Therefore, researchers have designed novel piperazine derivatives with various biological activities, including antiviral, antibacterial, and antifungal properties. In this study, a new series of 2‐(4‐((5‐bromo‐2‐methoxyphenyl)sulfonyl) piperazine‐1‐yl) acetamide derivatives (7a‐l) were synthesized and their structures were identified using 1H‐NMR, 13C‐NMR, and HRMS spectroscopic methods. The in vitro antimicrobial activity of these compounds was tested against four bacterial strains and two fungi strains. Some of the sulfonyl piperazine derivatives (7d, 7e, 7f, 7j, 7k, and 7l) exhibited relatively good antimicrobial and antifungal activities compared to standard drugs. Further analysis using computational docking confirmed strong binding interactions, aligning with our results. Our compounds exhibited improved potency compared to existing standard treatments. [ABSTRACT FROM AUTHOR]

Repeated epidemics caused by bacterial and fungal diseases pose a threat to global crop yields and food security, therefore, updating the structure of existing microbicides and improving the pesticide bioavailability are challenging tasks, perhaps planning to develop versatile supramolecular antimicrobial materials. Here, a low‐cost multifunctional supramolecular complex, named FT6@β‐CD, is constructed by host‐guest encapsulation of a thienyl‐engineered ingredient (FT6) into β‐cyclodextrin. This integrated architecture can significantly reduce the bounce and splash behaviors of droplets, improve the wetting performance, and eventually acquire excellent foliar deposition and targeted delivery. Whereafter, FT6@β‐CD can inhibit the transcription of type III secretion system (T3SS)‐associated genes, hypersensitive reaction, and final pathogenicity from a destructive pathogen Xanthomonas oryzae pv. oryzae (Xoo). Importantly, at a lower dosage of 200 µg mL−1, FT6@β‐CD presented excellent in vivo control effects (protection 48.1%, curative 50.1%) against Xoo, remarkably better than the commercial bactericidal formulation thiodiazole‐copper. Additionally, other supramolecular antifungal materials (FT24/FT25@HP‐β‐CD/β‐CD/Me‐β‐CD) constructed in this study can effectively treat Botryosphaeria dothidea and Botrytis cinerea with higher control efficiencies of 86.8% and 90.1% at 200 µg mL−1, respectively. This study provides a bright guidance for developing low‐cost, green, and eco‐friendly supramolecular microbicides for controlling agricultural diseases. [ABSTRACT FROM AUTHOR]

Cordyceps militaris, a medicinal fungus, has gained considerable attention owing to its potential health benefits, notably the production of bioactive compounds such as cordycepin. Cordycepin possesses significant antifungal, antibacterial, and antiviral properties. The present study focused on optimizing the fermentation conditions for C. militaris to boost the production of mycelia and cordycepin, alongside investigating its antifungal properties using in silico and in vitro approaches. The optimal conditions, yielding the highest cordycepin and mycelial biomass, were a temperature of 20°C and a pH range of 4–6, with glucose and sucrose as carbon sources and yeast extract and casein hydrolysate as nitrogen sources. Under these conditions, cordycepin production peaked at low pH (600–1000 mg/L) and with carbon and maltose (400–500 mg/L). The low temperature favored cordycepin production (400 mg/L), whereas casein hydrolysate as a nitrogen source boosted cordycepin yield (600 mg/L). The docking analysis indicated that cordycepin had the highest binding affinity for the tubulin beta chain 2 (−10.4 kcal/mol) compared to the fungicide tebuconazole (−7.9 kcal/mol for both targets). The in silico results were corroborated by in vitro studies, where the mycelial extract of C. militaris inhibited approximately 75% of fungal growth at a concentration of 6000 ppm. These findings suggest that optimizing fermentation conditions significantly enhances cordycepin production, and cordycepin shows antifungal solid activity, making it a promising agent for biocontrol in agriculture. [ABSTRACT FROM AUTHOR]

Antimicrobial resistance is a pressing global health concern, demanding the development of novel antimicrobial agents. Quinoline derivatives emerge as promising candidates with their diverse chemical structures and recognized bioactive properties. This study aimed to investigate the antimicrobial potency of newly synthesized quinoline derivatives against Candida albicans and five bacterial strains, which are responsible for various infections and have exhibited varying degrees of antibiotic resistance. A series of quinoline derivatives were synthesized through simple structural modifications, such as the inclusion of nitro, amino, and hydrazino groups, or using the molecular hybridization strategy, involving the combination of quinoline and 1,2,3‐triazoles. None of the compounds showed promising activity against the bacterial strains. However, a promising fungistatic effect was observed against C. albicans. In this test, two of the compounds showed lower MIC values than fluconazole (25 μg/mL). In addition, the most promising compounds showed high affinity for the enzyme lanosterol 14 alpha demethylase, due to the low energy values found (−7.6 and −8.2 kcal/mol). Our study offers new avenues for future drug development in the fight against antimicrobial resistance. [ABSTRACT FROM AUTHOR]

Background Methods Results Conclusion Coccidioidomycosis may cause severe disseminated disease and mortality among lung transplant recipients. A strategy of lifelong azole prophylaxis was previously associated with low rates of coccidioidomycosis. Whether lung transplant recipients relocating to the Coccidioides endemic region are also at risk and would benefit from antifungal prophylaxis is unknown.Lung transplant recipients transplanted at an outside center with low Coccidioides endemicity before relocating for post‐transplant follow‐up at a transplant center in Phoenix, Arizona from January 2013 to March 2024 were included. The primary outcome was proven or probable coccidioidomycosis per Mycoses Study Group consensus definitions.Forty lung transplant recipients were included, with 62.5% not receiving antifungal prophylaxis at the time of transfer. The median time from transplant to relocation was 34 months. Of those not on prophylaxis, 96% were initiated on azole therapy at the first clinic visit, with 72% prescribed itraconazole. Coccidioides serologic testing was performed in 30% of the cohort, most often in the context of a broad diagnostic work‐up for suspected infection during hospitalization. After a median follow‐up of 31 months, one case (2.5%) of proven pulmonary coccidioidomycosis was identified, occurring 4.8 years post‐transplant and >2 years post‐transfer in a cystic fibrosis patient who had a pause in fluconazole prophylaxis for >1 month prior to diagnosis due to gastrointestinal intolerance and access issues. The patient was treated and maintained on isavuconazole without complications.Azole antifungal prophylaxis was associated with a low rate of coccidioidomycosis among lung transplant recipients relocating to the highly endemic region. [ABSTRACT FROM AUTHOR]

Purpose: To develop a biocompatible denture base resin/TiO2 nanocomposite material with antifungal characteristics that is suitable for 3D‐printing denture bases. Materials and Methods: TiO2 nanoparticles (NPs) with a 0.10, 0.25, 0.50, and 0.75 weight percent (wt.%) were incorporated into a commercially available 3D‐printed resin material. The resulting nanocomposite material was analyzed using Lactate dehydrogenase (LDH) and AlamarBlue (AB) assays for biocompatibility testing with human gingival fibroblasts (HGF). The composite material was also tested for its antifungal efficacy against Candida albicans. Fourier transform infrared (FTIR) and Energy Dispersive X‐ray Spectroscopy (EDX) mapping were conducted to assess the surface coating and the dispersion of the NPs. Results: LDH and AB assays confirmed the biocompatibility of the material showing cell proliferation at a rate of nearly 100% at day 10, with a cytotoxicity of less than 13% of the cells at day 10. The concentrations of 0.10, 0.25, and 0.50 wt.% caused a significant reduction (p < 0.05) in the number of candida cells attached to the surface of the specimens (p < 0.05), while 0.75 wt.% did not show any significant difference compared to the control (no TiO2 NPs) (p > 0.05). FTIR and EDX analysis confirmed the presence of TiO2 NPs within the nanocomposite material with a homogenous dispersion for 0.10 and 0.25 wt.% groups and an aggregation of the NPs within the material at higher concentrations. Conclusion: The addition of TiO2 NPs into 3D‐printed denture base resin proved to have an antifungal effect against Candida albicans. The resultant nanocomposite material was a biocompatible material with HGFs and was successfully used for 3D printing. [ABSTRACT FROM AUTHOR]

This study discusses the micro‐level structural details of Cichorieae pollen sources elucidated by scanning electron microscopy (SEM) and explains their symmetry and morphometry. The in‐depth knowledge from the electron ultrastructure of Asteraceae pollen has provided insights into enhanced pollen morphology, and the antimicrobial significance of species under study presents novel avenues for their natural defense mechanisms in the development of antimicrobial agents. In this research, both quantitative and qualitative features of pollen were examined. The pollen grains are prolate‐spheroidal and oblate‐spheroidal in shape, characterized by a maximum polar diameter of 55.6–61.0 μm and a maximum equatorial distance of 68.3–74.4 μm. SEM reveals various configurations such as echinate perforate‐tectate, psilate, and echino‐lophate perforate. The Cichorieae species have significant antimicrobial efficacy and are promising sources for the development of novel antimicrobial drugs with potential implications in pharmaceutical and healthcare industries. SEM analysis of Cichorieae pollens has provided remarkable insights into their unique structures, revealing diverse shapes and surface ornamentations, which can be used for accurate Asteraceae species identification. Research Highlights: SEM provides unique pollen surface structures and patterns of Chicory pollen grains.Chemical composition of Chicory botanical sources provides valuable information on their potential as antimicrobial agents.SEM imaging reveals specialized fenestrate grain structures of taxonomic importance. [ABSTRACT FROM AUTHOR]

With the steady rise in antifungal resistance amongst clinically important yeasts, antifungal drug discovery remains of the utmost importance. To determine the potential of some honeys as alternative antifungal agents, we quantified the antifungal activity of 12 Western Australian honey samples, two Manuka honey samples and an artificial honey against 10 yeast isolates including clinical and reference strains. Results showed that the tested honeys varied in activity, and yeasts species also differed in susceptibility, with minimum inhibitory concentrations (MICs) determined by broth microdilution ranging from 8% to >44% w/v honey. Honeys with the highest overall activity were derived from Blackbutt (Eucalyptus patens), Jarrah (E. marginata), and Karri (E. diversicolor). The optical density of each MIC microtitre plate was determined after incubation and showed that at relatively low concentrations of honey the growth of all yeasts was enhanced compared to the untreated control, whereas at and above approximately 12% w/v, honeys exerted a dose‐dependent growth inhibitory effect, the extent of which varied by honey type. Time‐kill studies with 64% w/v honey showed that all eight of the natural honeys tested had greater fungicidal activity than the comparator artificial honey. Our findings suggest that the specific nectar‐derived phytochemicals present within each honey play an important role in antifungal activity, and support the notion that activity is due to a combination of factors including osmotic activity, hydrogen peroxide and phytochemical compounds. These data indicate that honey is worthy of further investigation as a potential therapeutic agent for superficial yeast infections. Take‐away: All honeys tested demonstrated dose dependent inhibition of tested yeasts.Honey, at high concentrations, is fungicidal for tested yeasts.A combination of osmotic, physicochemical, and phytochemicals are responsible. [ABSTRACT FROM AUTHOR]

Sheath blight of rice is a global disease that significantly reduces rice yield. This study reports the antifungal activity of an active compound of essential oil, thymol, at different concentrations against Rhizoctonia solani (strain RS‐Gvt). In vitro assay results indicated that thymol concentrations (0.5 mg mL−1 and 0.25 mg mL−1) completely inhibited (100%) the mycelial growth of RS‐Gvt (p ≤ 0.01). Microscopic observations of thymol‐treated mycelium of RS‐Gvt at 0.0312 mg mL−1 and above concentrations, revealed a distorted mycelial morphology with deformed hyphae. Hyphae showed a bead‐like appearance, reduction in size, and constriction of the hyphae at uneven points with increased hyphal density often entangling with each other. Further, an on‐field experiment was conducted to study the field bio‐efficacy of thymol for two consecutive Kharif seasons of 2022 and 2023 using a factorial RCBD design. The disease severity was measured as the percent disease index (PDI), and the results of two seasons were pooled. Pathogen (RS‐Gvt) and thymol were inoculated in different combinations/methods as main treatments (M1‐M3), and concentrations of thymol (0.0625–1.0 mg ML−1) as sub‐treatments. The results indicated that all two factors significantly (P = 0.05) influenced the PDI and grain yield. The pooled data of two seasons indicated a significant difference between the main treatments (M1: RS‐Gvt + thymol together; M2: thymol sprayed first followed by RS‐Gvt; M3: RS‐Gvt first followed by thymol spray) on PDI (53.39–59.67) and grain yield (4.16–4.75 t ha−1). M1 exhibited a lower PDI (53.39) and a higher grain yield (4.75 t ha−1) compared to M2 and M3, indicating a protective mode of action of thymol against sheath blight disease of rice. The sub‐treatments have shown significant variation in PDI and grain yield. The PDI and grain yield ranged from 33.70 (at 1 mg mL−1) to 66.21 (at 0.0625 mg mL−1) and 4.18 (at 1 mg mL−1) to 5.26 (at 0.0625 mg mL−1) t ha−1, respectively, among the thymol concentrations. This indicates that increasing concentrations of thymol have negatively influenced the PDI and positively impacted the yield. Therefore, the spray of 1 mg mL−1 of thymol at the potential disease‐infection stage is most effective in controlling the sheath blight disease of rice. This study provides an alternative green bioactive compound for controlling the sheath blight disease, and thymol can be included in developing eco‐friendly integrated disease management practices. © 2024 Society of Chemical Industry. [ABSTRACT FROM AUTHOR]

Medicinal chemistry highly values the benzimidazole scaffold as a pharmacophore owing to its versatile range of biological functions. In the present study, 17 derivatives of 2‐aryl‐N1‐arylacetamido benzimidazoles 3(a–q) were synthesized by nucleophilic substitution reactions between different 2‐chloro‐N‐(aryl)‐acetamides 2(a–q) and 2‐(4‐chlorophenyl)‐1H‐benzo[d]imidazole (1) in N, N‐dimethylformamide, and evaluated for in vitro anti‐HIV and antifungal activities. Of these derivatives, compounds 3 a, 3 b, 3 i, and 3 n showed moderate inhibitory efficacy against HIV‐1 RT, whereas the remaining compounds showed negligible activity compared to the standard drug efavirenz. In contrast, most of the test compounds demonstrated significant efficacy against fungal strains such as Candida albicans and Aspergillus niger. Compounds 3 a, 3 f, 3 m, and 3 n were the most effective antifungal agents. We applied computational approaches to rationalize the potency of the newly synthesized inhibitors. [ABSTRACT FROM AUTHOR]

Synthesis of novel (E)‐N‐(4‐(substituted)benzylidene)‐6‐substituted‐1H‐pyrazolo[3,4‐b]quinoline‐1‐carbothioamides/carboxamides was achieved by the condensation of 6‐substituted‐1H‐pyrazolo[3,4‐b]quinoline‐1‐carbothioamides/carboxamides with substituted benzaldehydes in alcoholic medium in the presence of acetic acid. The structures of synthesized compounds are assigned on the basis of FT IR, 1H NMR, 13C NMR and Mass Spectral data. The compounds are subjected for their antibacterial, antifungal and DFT studies. Compounds, (E)‐6‐chloro‐N‐(4‐(dimethylamino)benzylidene)‐1H‐pyrazolo[3,4‐b]quinoline‐1‐carbothioamide (5 b), (E)‐6‐chloro‐N‐(4‐(dimethylamino)benzylidene)‐1H‐pyrazolo[3,4‐b]quinoline‐1‐carboxamide (5 f), and (E)‐6‐chloro‐N‐(4‐hydroxybenzylidene)‐1H‐pyrazolo[3,4‐b]quinoline‐1‐carboxamide (5 j) possessed pronounced antibacterial and antifungal activities due to their chemical structure. [ABSTRACT FROM AUTHOR]

Many invertebrates and vertebrates secrete mucus from their body surface, which plays a crucial role in protecting themselves from attacks by microorganism or predators. This study reports on the potential functions of mucus secreted from the body surface of larvae of the moth Phauda flammans (Walker) (Lepidoptera: Phaudidae). We tested whether the mucus could inhibit the growth of the fungus Beauveria bassiana PfBb (Bals.‐Criv.) Vuill. (Hypocreales) and attract and/or deter predators such as the crazy ant, Paratrechina longicornis (Latreille) (Hymenoptera: Formicidae), and the predatory bug Eocanthecona furcellata (Wolff) (Hemiptera: Pentatomidae). Our results showed that de‐ and rehydrated mucus concentrations of 0.5–1.0 mg mL−1 had an inhibitory effect on the conidial germination and colony growth of B. bassiana PfBb; however, P. flammans mucus did not significantly affect fungal sporulation. Raw mucus and mucus concentrations of 1.0–4.0 mg mL−1 attracted P. longicornis workers in a Y‐tube olfactometer, whereas the physical viscosity of raw mucus hindered their foraging for food in a laboratory test. The E. furcellata adults did not display a preference for the odour of P. flammans mucus. Therefore, P. flammans mucus may inhibit pathogenic microorganisms and attract or repel predators, but the mucus does not act as a complete deterrent. [ABSTRACT FROM AUTHOR]

This study focuses on the synthesis of azo‐thiosemicarbazone ligand, which is designed by reacting 2‐hydroxy‐5‐(phenyldiazenyl)benzaldehyde with hydrazine carbothioamide. Hence, this ligand was exploited for chelation with nickel and cupric salts in (1 M:1 L) molar ratio. These synthetics were structurally investigated using a variety of physical, analytical, and spectroscopic (1D/2D‐NMR, UV–Vis, FT‐IR, and E‐mass) tools as well as theoretically. The finding demonstrated that the resulting azo‐thiosemicarbazone (H4Azo‐TSC) bonded with the nickel and cupric ions as mono/di‐basic tridentate chelators, binding them via deprotonated phenolic oxygen, imino nitrogen, and thionic/thiol sulfur atoms adopting square planar geometry. The theoretical investigation was examined by DFT/B3LYP/LanL2dZ, including energetic parameters, HOMO‐LUMO energy gap, dipole moment, and geometrical optimization, which were applied to support the complexes' geometrical structure. The in vitro microbicidal activities of the azo‐thiosemicarbazone, compared with its Ni2+ and Cu2+ complexes, display superior activity over the metal complexes against different bacterial and fungal species. The anticancer efficacy of the synthetics was tested against human lung fibroblast (WI38) and mammary gland breast cancer (MCF‐7) compared with Doxorubicin as a standard drug. The cytotoxic efficiency of metallic complexes exceeded that of un‐chelated azo‐thiosemicarbazone. The most effective complex is Ni2+ complex with IC50 equal to 11.75 and 14.05 μg/ml, respectively. It has been demonstrated that Ni2+ and Cu2+ complexes are more biocompatible than free azo‐thiosemicarbazone; this finding may be related to the chelation process. [ABSTRACT FROM AUTHOR]

In this work, we sought to validate the use of Euphorbia calyptrata (L.), a Saharan and Mediterranean medicinal plant, in traditional pharmacopeia. GC‐MS/MS identified volatile compounds of potential therapeutic interest. Antioxidant tests were performed using β‐carotene decolorization, DPPH radical scavenging, FRAP, beta‐carotene bleaching, and TAC. The antimicrobial activity was evaluated on solid and liquid media for bacterial and fungal strains to determine the zone of inhibition and the minimum growth concentration (MIC) of the microbes tested. The hemolytic activity of these essential oils was assessed on red blood cells isolated from rat blood. Phytochemical characterization of the terpenic compounds by GC‐MS/MS revealed 31 compounds, with alpha‐Pinene dominating (35.96 %). The antioxidant power of the essential oils tested revealed an IC50 of 67.28 μg/mL (DPPH), EC50 of 80.25.08±1.42 μg/mL (FRAP), 94.83±2.11 μg/mL (beta carotene) and 985.07±0.70 μg/mL (TAC). Evaluating solid media's antibacterial and antifungal properties revealed a zone of inhibition between 10.28 mm and 25.80 mm and 31.48 and 34.21 mm, respectively. On liquid media, the MIC ranged from 10.27 μg/mL to 24.91 μg/mL for bacterial strains and from 9.32 μg/mL to 19.08 μg/mL for fungal strains. In molecular docking analysis, the compounds naphthalene, shogunal, and manol oxide showed the greatest activity against NADPH oxidase, with Glide G scores of −5.294, −5.218 and −5.161 kcal/mol, respectively. For antibacterial activity against E. coli beta‐ketoacyl‐[acyl carrier protein] synthase, the most potent molecules were cis‐Calamenene, alpha.‐Muurolene and Terpineol, with Glide G‐scores of −6.804, −6.424 and −6.313 kcal/mol, respectively. Hemolytic activity revealed a final inhibition of 9.42±0.33 % for a 100 μg/mL concentration. The essential oils tested have good antioxidant, antimicrobial, and hemolytic properties thanks to their rich phytochemical composition, and molecular docking analysis confirmed their biological potency. [ABSTRACT FROM AUTHOR]

Phellinus caribaeo‐quercicola is a basidiomycetous fungus, isolated as an endophyte in this study from the healthy and symptomless leaves of Inula racemosa Hook. f., an important medicinal herb growing in Kashmir Himalaya. This study combines morphological, molecular and phylogenetic techniques to identify the fungal endophyte, using the ITS sequence of nrDNA. A detached leaf assay was conducted to assess the pathogenicity of the fungal endophyte suggesting its mutually symbiotic relationship with the host. The authors also investigated the antifungal potential of the isolated endophytic strain to ascertain its use as a biocontrol agent. The study shows that P. caribaeo‐quercicola INL3‐2 strain exhibits biocontrol activity against four key fungal phytopathogens that cause significant agronomic and economic losses: Aspergillus flavus, Aspergillus niger, Fusarium solani, and Fusarium oxysporum. Notably, P. caribaeo‐quercicola INL3‐2 strain is highly effective against A. flavus, with an inhibition percentage of 57.63%. In addition, this study investigates the antioxidant activity of P. caribaeo‐quercicola INL3‐2 strain crude extracts using ethyl acetate and methanol as solvents. The results showed that the methanolic fraction of P. caribaeo‐quercicola exhibits potential as an antioxidant agent, with an IC50 value of 171.90 ± 1.15 µg/mL. This investigation is first of its kind and marks the initial report of this fungal basidiomycete, P. caribaeo‐quercicola, as an endophyte associated with a medicinal plant. The findings of this study highlight the potential of P. caribaeo‐quercicola INL3‐2 strain as a dual‐action agent with both biocontrol and antioxidant properties consistent with the medicinal properties of Inula racemosa. This endophytic fungus could be a promising source of natural compounds for use in agriculture, medicine, and beyond. [ABSTRACT FROM AUTHOR]

Herein, single step biosynthesis of silver nanoparticles (AgNPs) is reported by using AgNO3 and Monstera deliciosa (MD) leaf extract. Spherical AgNPs are obtained with difference in particle sizes and antibacterial activities using two sets of MD leaf extract having different heating periods 5 and 10 min. They are characterized by UV–vis spectroscopy, X‐ray diffraction (XRD), Zeta potential, Attenuated Total Reflectance Infrared Spectroscopy (ATR‐IR), and Field Emission Scanning Electron Microscopy (FE‐SEM). Dynamic Light Scattering (DLS) studies propose two types of AgNPs have hydrodynamic diameters of 104 and 80 nm. Nuclear Magnetic Resonance (NMR), Gas Chromatography‐Mass Spectrometry (GC‐MS), and High Resolution−Mass Spectrometry (HR‐MS) studies, which reveal the presence of various phytochemicals found in MD leaf extract. These biomolecules play a vital role as stabilizing and reducing agents to fabricate stable AgNPs. These AgNPs exhibit strong antibacterial activities having effective zone of inhibition for both Gram‐positive (Staphylococcus aureus, Bacillus subtilis) and Gram‐negative (Escherichia coli, Pseudomonas aeruginosa) microorganisms, nonetheless AgNPs against different fungi (Penicillium sp., Aspergillus flavus, Fusarium oxysporum, Rhizoctonia solani) show non‐antifungal characteristics because of their inert nature. This study suggests that AgNPs can be used in treating bacterial infections and drug delivery also for several therapeutic and diagnostic applications. [ABSTRACT FROM AUTHOR]

In the present study, the aimed enamines 3 a–j were synthesized with yield ranging between 65 and 81 % by the reaction of 5‐((dimethylamino)methylene)‐1,3‐dimethylpyrimidine‐2,4,6(1H,3H,5H) ‐trione (2) with different amines at room temperature (25 °C). The structures of all synthesized compounds were characterized using different spectroscopic techniques. Molecular docking studies of the new compounds 3 a–j were carried out with human estrogen receptor (hER) enzyme to evaluate their activities as an effective drug molecules. It was investigated that the compounds 3 b, 3 e, 3 f and 3 j revealed the best binding affinities. All new compounds were evaluated towards antifungal activities, which conceded that the compound 3 e displayed a remarkable antifungal activity compared to the Fluconazole and Nystatin, and its Minimum Inhibitory Concentration (MIC) found to be 0.011 mM, while for Fluconazole the MIC value exhibited at 0.046 mM. Additionally, the toxicity for the new compounds found to be better than tamoxifen on MCF‐7 cells and among these molecules, the compound 3 e displayed the lowest IC50 value. [ABSTRACT FROM AUTHOR]

A series of novel 2,3,5‐trisubstituted thiazolidinone derivatives was designed and synthesized. Compounds were tested for their antimicrobial and antitubercular activities. Compounds 3‐(2,4‐difluorobenzyl)‐5‐[(5‐methylfuran‐2‐yl)methylidene]‐2‐(phenylimino)‐1,3‐thiazolidin‐4‐one (5 c) and 3‐(2,4‐difluorobenzyl)‐2‐((3‐fluorophenyl)imino)‐5‐((Z)‐4‐hydroxybenzylidene) thiazolidin‐4‐one (6 f) exhibited remarkable antimicrobial activity against Klebsiella pneumoniae and Escherichia coli respectively. All compounds except 3‐(2,4‐difluorobenzyl)‐5‐((3‐(4‐fluorophenyl)‐1‐phenyl‐1H‐pyrazol‐4‐yl)methylene)‐2‐(phenylimino)thiazolidin‐4‐one (5 a) and (6 f) exposed excellent antitubercular activity in comparison with the standard drugs against H37RV strain of Mycobacterium tuberculosis (ATCC No‐ 27294). In addition, molecular docking and dynamic simulations studies were performed with E. coli Mur B (EMB) (PDB ID: 2Q85), Aspergillus fumigatus sterol 14‐alpha demethylase (ASD) (PDB ID: 4UYM) and Mycobacterium tuberculosis pantothenate synthetase (MPS) (PDB ID: 3IVX) proteins against all compounds and the most potent compound (5 c) displayed higher binding proficiency. These compounds may serve as lead compounds for further optimization to achieve promising therapeutic properties. [ABSTRACT FROM AUTHOR]

The development of innovative antifungal medications to address the issues of indiscriminate antifungal use contributes to certain antifungal drug resistance. To tackle this issue, we have designed and synthesized novel amino acids naphthalene scaffolds (6 a–6 i) (Scheme 1) by acid amine coupling between compound 5 and various amino acids. Moreover, we evaluated the antifungal, anti‐bacterial and antimalarial activities of synthesized derivatives. Among them, compounds Met (6 a), Phe (6 c), Lys (6 d), Ser (6 f), and Tyr (6 i) expressed excellent antifungal activity at a minimum inhibitory concentration (MIC) value of 250 μg/mL against Candida albicans compared to standard drug griseofulvin (500 μg/mL). The antibacterial assay results showed that compound Met (6 a) exhibited effective antibacterial activity at MIC value at 50 and 62.5 μg/mL against Streptococcus pyogenes and Pseudomonas aeruginosa respectively, and compound Trp (6 g) showed very good antibacterial activity at MIC 62.5 μg/mL against Staphylococcus aureus. The antimalarial activity of synthesized compoundsVal (6 b) and Lys (6 d) showed moderately active with mean IC50 of 0.69 and 0.47 μg/mL, respectively compared with standard drug quinine (IC50=0.26 μg/mL). Also, a molecular docking study was performed to demonstrate the binding energy of synthesized scaffoldswith effective interaction with various proteins. The compound Met (6 a) showed that the highest binding affinity (binding energy: −7.1 kcal/mol) which interacted more effectively with VAL 120 (2.90 Å). [ABSTRACT FROM AUTHOR]

Infections caused by Candida species, especially Candida albicans, threaten the public health and create economic burden. Shortage of antifungals and emergence of drug resistance call for new antifungal therapies while natural products were attractive sources for developing new drugs. In our study, fangchinoline, a bis‐benzylisoquinoline alkaloid from Chinese herb Stephania tetrandra S. Moore, exerted antifungal effects on planktonic growth of several Candida species including C. albicans, with MIC no more than 50 μg/mL. In addition, results from microscopic, MTT and XTT reduction assays showed that fangchinoline had inhibitory activities against the multiple virulence factors of C. albicans, such as adhesion, hyphal growth and biofilm formation. Furthermore, this compound could also suppress the metabolic activity of preformed C. albicans biofilms. PI staining, followed by confocal laser scanning microscope (CLSM) analysis showed that fangchinoline can elevate permeability of cell membrane. DCFH‐DA staining suggested its anti‐Candida mechanism also involved overproduction of intracellular ROS, which was further confirmed by N‐acetyl‐cysteine rescue tests. Moreover, fangchinoline showed synergy with three antifungal drugs (amphotericin B, fluconazole and caspofungin), further indicating its potential use in treating C. albicans infections. Therefore, these results indicated that fangchinoline could be a potential candidate for developing anti‐Candida therapies. [ABSTRACT FROM AUTHOR]

Background: Two approaches are used to manage invasive fungal disease (IFD) in febrile neutropenic patients viz. empirical therapy (without attempting to confirm the diagnosis), or pre‐emptive therapy (after screening tests for IFD). Objective: This systematic review was undertaken to compare these approaches in children. Methods: We searched PubMed, EMBASE, Cochrane Library, Scopus, Web of Science, CINAHL, Clinical Trial Registries and grey literature, for randomized controlled trials (RCT) comparing empirical versus pre‐emptive antifungal therapy in children with FN suspected to have IFD. We used the Cochrane Risk of bias 2 tool for quality assessment, and evaluated the certainty of evidence using the GRADE approach. Results: We identified 7989 citations. Stepwise screening identified only one relevant RCT that administered empirical (n = 73) or pre‐emptive (n = 76) antifungal therapy. There were no significant differences in all‐cause mortality (RR 1.56, 95% CI: 0.46, 5.31), IFD mortality (RR 1.04, 95% CI:0.15, 7.20) and other clinically important outcomes such as duration of fever, duration of hospitalization and proportion requiring ICU admission. There were no safety data reported. The number of days of antifungal therapy was significantly lower in the pre‐emptive therapy arm. The certainty of evidence for all outcomes was 'moderate'. Conclusions: This systematic review highlighted the paucity of data, comparing empirical versus pre‐emptive antifungal therapy in children with febrile neutropenia having suspected invasive fungal disease. Data from a single included trial suggests that both approaches may be comparable in research settings. Robust trials are warranted to address the gap in existing knowledge about the optimal approach in clinical practice. [ABSTRACT FROM AUTHOR]

Carbon dots (CDs) are an emerging class of carbon nanoparticles, which for their characteristics have found applications in many fields such as catalysis, materials and biomedicine. Within this context, the application of CDs as antibacterial agents has received much attention in very recent years, while their use as antifungal nanoparticles has been scarcely investigated. Here we report a systematic investigation of the surface functional groups of CDs to study their influence on these nanoparticles' against Candida albicans. Three classes of CDs have been synthesised and fully characterized. A thorough in vitro and in vivo biological screening against C. albicans was performed to test their antifungal, antiadhesion and antibiofilm formation activities. Moreover, the interaction with C. albicans cells was investigated by microscopic analysis. Our results evidence how the presence of a positively polarised surface results crucial for the internalization into COS‐7 cells. Positively charged nanoparticles were also able to inhibit adhesion and biofilm formation, to interact with the cellular membrane of C. albicans, and to increase the survival of G. mellonella infected larvae after the injection with positive nanoparticles. The antifungal activity of CDs and their extremely low toxicity may represent a new strategy to combat infections sustained by C.albicans. [ABSTRACT FROM AUTHOR]

The synthesis of Cyanobacteria‐mediated nanoparticles has attracted great attention due to its ecofriendly, cost‐effective and biocompatible properties. Silver nanoparticles (AgNPs) are used in different areas such as medicine, household products, disinfectants or food storage. The present study aimed the biosynthesis of AgNPs from Cyanobacterial Chroococcus sp. and their antimicrobial activities on some important pathogen bacterial species. According to the obtained data, optimal conditions for synthesis of AgNPs were extract rate 3 : 1 v/v (cell extract/AgNO3), silver salt concentration 10 mM, pH 7, temperature 60 °C and time 30 minutes. The surface plasmon resonance peak of AgNPs was observed at 420–430 nm, and AgNPs were well‐dispersed spherical with an average size of 11–13 nm in diameter by TEM. SEM‐EDX analysis revealed a strong signal of silver. With FTIR analyzes, shift in the absorption bands after the AgNPs formation was confirmed. X‐ray diffraction analysis exhibited that the AgNPs were cubic crystalline shape. Zeta potential of AgNPs showed ‐ 20 mV. The AgNPs strong showed antibacterial activity on an opportunistic bacterial pathogens of Micococcus luteus, Bacillus subtilis and Pseudomonas aeroginosa. The effective and rapid synthesis of Chroococcus‐mediated AgNPs and their strong antimicrobial effects can create an important potential for their use in biomedical and environmental applications. [ABSTRACT FROM AUTHOR]

The production of nanoparticles (NPs) using biological methods may lead to the enhancement of clean, non‐hazardous, and environmentally acceptable procedures. With this context, in the present study silver nanoparticles (AgNPs) were synthesized using the flower extract of Aerva lanata (A. lanata). The following techniques, including UV–visible spectroscopy, XRD, Scanning Electron Microscopy (SEM), and Fourier Transform Infrared Spectroscopy (FTIR), are used to study the crystalline nature, size, shape, and elemental composition of the biosynthesized AgNPs, and antimicrobial applications of the NPs also studied. In UV–visible spectroscopy results a strong absorbance peak at 425 nm confirmed the AgNPs. The SEM results confirmed the spherical shape of the NPs and their average size of 45.05 nm. X‐ray diffractometry XRD spectra confirmed the crystalline nature of the AgNPs. Against the DPPH (2,2‐diphenyl‐1‐picrylhydrazyl), nitric oxide and superoxide radicals, Alf‐AgNPs and ascorbic acid had significant scavenging effects at higher concentration of 250 μg/mL, exhibited 65.76 ± 0.41% and 86.42 ± 0.69%, 78.39 ± 0.49% and 72.72 ± 0.14% and 70.79 ± 0.87% and 72.79 ± 0.33% inhibition, respectively. As produced AgNPs had strong antibacterial and moderate antifungal activities against pathogenic test bacterial strains viz. Staphylococcus aureus (S. aureus), Bacillus subtilis (B. subtilis), Escherichia coli (E. coli), and Klebsiella pneumonia (K. pneumonia) with the maximum zone of inhibition 15 ± 1.07 mm, 12 ± 0.96 mm, 14 ± 1.05 mm, and 15 ± 2.54 mm, respectively at maximum (75 μg/mL) concentration of AgNPs, and the zone of inhibition of fungal strains Aspergillus fumigatus (A. fumigatus) (9 ± 0.67 mm) and Candida albicans (C. albicans) (7 ± 0.75 mm) at 75 μg/mL. It was eventually concluded that the biosynthesized Alf‐AgNPs showed promising antioxidant and antimicrobial agents with very low concentrations. [ABSTRACT FROM AUTHOR]

Aims: Ibrutinib is used in the treatment of certain B‐cell malignancies. Due to its CYP3A4‐mediated metabolism and highly variable pharmacokinetics, it is prone to potentially harmful drug‐drug interactions. Methods: In a randomized, placebo‐controlled, three‐phase crossover study, we examined the effect of the CYP3A4‐inhibiting antifungal posaconazole on ibrutinib pharmacokinetics. Eleven healthy participants ingested repeated doses of 300 mg of posaconazole either in the morning or in the evening, or placebo. A single dose of ibrutinib (30, 70 or 140 mg, respectively) was administered at 9 AM, 1 or 12 h after the preceding posaconazole/placebo dose. Results: On average, morning posaconazole increased the dose‐adjusted geometric mean area under the plasma concentration‐time curve from zero to infinity (AUC0‐∞) and peak plasma concentration (Cmax) of ibrutinib 9.5‐fold (90% confidence interval [CI] 6.3‐14.3, P < 0.001) and 8.5‐fold (90% CI 5.7‐12.8, P < 0.001), respectively, while evening posaconazole increased those 10.3‐fold (90% CI 6.7‐16.0, P < 0.001) and 8.2‐fold (90% CI 5.2‐13.2, P < 0.001), respectively. Posaconazole had no significant effect on the half‐life of ibrutinib, but substantially reduced the metabolite PCI‐45227 to ibrutinib AUC0‐∞ ratio. There were no significant differences in ibrutinib pharmacokinetics between morning and evening posaconazole phases. Conclusions: Posaconazole increases ibrutinib exposure substantially, by about 10‐fold. This interaction cannot be avoided by dosing the drugs 12 h apart. In general, a 70‐mg daily dose of ibrutinib should not be exceeded during posaconazole treatment to avoid potentially toxic systemic ibrutinib concentrations. [ABSTRACT FROM AUTHOR]

Background: Fungal infections are common among pregnant people. Recent studies suggest positive associations between oral antifungals used to treat fungal infections and congenital heart defects (CHDs). Methods: We estimated associations between first trimester antifungal use and 20 major, specific CHDs using data from the National Birth Defects Prevention Study (NBDPS), a multi‐site, case–control study that included pregnancies with estimated delivery dates from October 1997 through December 2011. Infants with CHDs ("cases") were ascertained from 10 birth defect surveillance programs. Live born infants without major birth defects ("controls") were randomly selected from birth records or hospital discharge lists. First trimester antifungal use was self‐reported via maternal interview. We estimated adjusted odds ratios (AORs) and 95% confidence intervals (CIs) using logistic regression with Firth's penalized likelihood. Results: First trimester antifungal use was reported by 148/11,653 (1.3%) case and 123/11,427 (1.1%) control participants. We estimated AORs for 12 CHDs; six had AORs >1.5 (tetralogy of Fallot, double outlet right ventricle with transposition of the great arteries [DORV‐TGA], atrioventricular septal defect, hypoplastic left heart syndrome, pulmonary atresia, muscular ventricular septal defect), and one (pulmonary valve stenosis) had an AOR <0.7. All CIs included the null, except for DORV‐TGA. Conclusions: First trimester antifungal use was rare. We observed some positive associations for several specific CHDs in our analysis, although the CIs largely included the null. Results do not support a large increase in risk, but smaller increases in risk for certain CHD cannot be ruled out. [ABSTRACT FROM AUTHOR]

BACKGROUND: Crop diseases caused by plant pathogenic fungi and bacteria have led to substantial losses in global food production. Chemical pesticides have been widely used as a primary means to mitigate these issues. Nevertheless, the persistent and excessive use of pesticides has resulted in the emergence of microbial resistance. Moreover, the improper application and excessive utilization of pesticides can contribute to environmental pollution and the persistence of pesticide residues. Consequently, the development of novel and highly effective bactericides and fungicides to combat plant pathogens holds immense practical importance. RESULTS: A series of uracil hydrazones IV‐B was deliberately designed and evaluated for their antimicrobial efficacy. The results of bioassays indicated that most IV‐B exhibited >80% inhibition against the fungal species Monilia fructigena and Sclerotium rolfsii, as well as the bacterial species Clavibacter michiganensis subsp. michiganensis, Xanthomonas oryzae pv. oryzae, and Ralstonia solanacearum, at 50 μg/mL in vitro. In vivo, IV‐B20 showed 89.9% of curative and 71.8% of protective activities against C. michiganensis subsp. michiganensis at 100 μg/mL superior to thiodiazole copper and copper hydroxide. IV‐B20 also showed excellent protective activity against M. fructigena (96.3% at 200 μg/mL) and S. rolfsii (80.4% at 1000 μg/mL), which were greater than chlorothalonil and equivalent to thifluzamide. Mechanistic studies revealed that IV‐B20 induced oxidative damage in pathogenic bacteria and promoted the leakage of cellular contents. CONCLUSION: This study suggests that IV‐B20 with uracil hydrazone skeleton has great potential as an antimicrobial candidate. These findings lay a foundation for practical application in agriculture. © 2023 Society of Chemical Industry. [ABSTRACT FROM AUTHOR]

Enantiomerically enriched phosphorus‐containing α‐amino acids were synthesized by the method of asymmetric synthesis, using Ni(II) square planar complex of dehydroalanine as an initial complex. After acidic hydrolysis, α‐amino acids with high enantiomeric purity were isolated. At the next stage, Fmoc derivatives of the obtained α‐amino acids were synthesized (ee >99 %). Synthesized α‐amino acids and their Fmoc derivatives exhibited anticholinesterase activity, inhibiting AChE and BuChE. At the same time, the antiacetylcholinesterase activity ranged from 14 to 77 %, and (S)‐2‐((((9H‐fluoren‐9‐yl)methoxy)carbonyl)amino)‐3‐(diisopropoxyphosphoryl) propanoic acid showed relatively high activity (77.9 %). In the case of studying the antibutyrylcholinesterase properties, the activity ranged from 4 to 71 %, and (S)‐2‐amino‐3‐(diisopropoxyphosphoryl)propanoic acid showed high activity (71 %). [ABSTRACT FROM AUTHOR]

Introduction: Microsporum canis is the most common dermatophyte infecting pets and their owners, and its long duration of treatment and increasing rate of drug resistance have caused the attention of researchers to be directed towards the use of nanoparticles and new alternatives for treatment. This study investigated the antifungal effects of zinc oxide (ZnO) nanoparticles on clinical isolates of M. canis in dogs and cats and subtilisin 1 (SUB1) gene expression. Materials and methods: Zinc oxide nanoparticles were prepared using the wet chemical method at a concentration of 4000 ppm. Its antifungal potential was evaluated at concentrations of 62.5–4000 ppm by disk diffusion and microdilution methods against 10 isolates of M. canis. The effect of this product on SUB1 gene expression was investigated by quantitative real‐time PCR method. Results: The results of the disk diffusion test showed that the highest inhibitory diameter was at the highest concentration of ZnO nanoparticles (34 mm), and the inhibitory zone was observed in dilutions up to 250 ppm. The minimum inhibitory concentration (MIC) of ZnO nanoparticles was between 250 and 500 ppm, and the minimum fungicidal concentration was between 500 and 1000 ppm. There was a significant reduction in SUB1 gene expression in sub‐MIC concentration (125–250 ppm) (p < 0.05). Conclusion: This study showed that ZnO nanoparticles have a concentration‐dependent inhibitory effect on M. canis. Moreover, ZnO nanoparticles could decrease the expression of SUB1, an enzyme involved in fungi adhesion to the epidermis. Nevertheless, more studies must be done in the future to determine the possible side effects and safety of ZnO nanoparticles along with their efficacy in vivo. [ABSTRACT FROM AUTHOR]

Cu alkyne‐azide cycloaddition was used to easily synthesize a library of novel heterocycles containing benzimidazole and piperidine based 1,2,3‐triazole(7a–7l) derivatives. The synthesized analogs were characterized by various spectroscopic techniques like FTIR, 1H nuclear magnetic resonance (NMR), 13C NMR, and mass spectrometry. All these novel bioactive compounds (7a–7l) were evaluated for in vitro antibacterial and antifungal efficacy. Compound 7k exhibited appreciable potent activity against Escherichia coli strain. Compounds 7a, 7b, 7f, and 7i showed excellent potent activity against all bacterial strains. Compound 7b, 7c, 7d, and 7g derivatives showed excellent effects when tested in vitro for antifungal activity against various fungal strains. Additionally, a molecular docking investigation revealed that compound 7k has the ability to bind to the active site of the E. coli DNA gyrase subunit protein and form hydrogen bonds with significant amino acid residues Asp73 and Asp49 in the active sites. In a 100 ns molecular dynamics simulation, the E. coli DNA gyrase protein's steady capacity to bind compound 7k was shown by the low measured root mean square deviation, which was an indication of the complex's conformational stability. [ABSTRACT FROM AUTHOR]

Novel bio‐based, biodegradable packaging material was developed with multi‐functional properties of good mechanical strength, potent biocompatibility, and antifungal attributes, predominantly against fungi vital in food spoilage. Biodegradable polymer composites were prepared with a natural antifungal agent, nystatin (Nyst), by melt processing technique for the first time. Initially, Polycaprolactone (PCL) was melt‐mixed with various percentages of nystatin to produce nystatin‐encapsulated PCL composites (PCL/Nyst). The as‐prepared PCL/Nyst composites were melt‐mixed with polylactic acid (PLA) to produce nystatin PLA/PCL blend composites. Subsequently, the prepared composites were compression molded in the form of films (1 mm) for further characterization. The composite's structural properties were evaluated by SEM, FTIR, mechanical and thermal studies. In addition, the composites were tested in vitro against a panel of pathogenic fungi and for antibiofilm attributes, specifically against three Candida species (C. albicans ATCC10231, C. parapsilosis ATCC22019, and C. glabrata ATCC2001), and foodborne Penicillium sp. All the composites containing 2 to 20 wt% nystatin displayed good activity and sustained nystatin release for up to 4 days. Thus, the overall study demonstrates the potential application of natural antifungal agents in biodegradable polymers to produce novel composite films for antimicrobial packaging without inducing any toxicity, judged from the toxicity assay using nematode Caenorhabditis elegans. [ABSTRACT FROM AUTHOR]

Background: The optimal timing for therapeutic drug monitoring (TDM) of voriconazole in Asians, who have higher rates of poor metabolisers than non‐Asians, is unclear. This can cause unexpectedly high concentrations and delays in reaching steady‐state levels. Objectives: To determine the appropriate timing of TDM in Japanese patients receiving voriconazole. Patients/Methods: Trough levels (Cmin) were measured on days 3–5 (recommended timing, RT) and days 6–14 (delayed timing, DT) after starting voriconazole in patients receiving an appropriate dosage. Considering bioavailability, Cmin was only compared in patients receiving oral voriconazole. Results: A total of 289 and 186 patients were included in the safety and pharmacokinetic analyses, respectively. There was a significant difference in Cmin measured no later than and after day 5 (3.59 ± 2.12 [RT] vs. 4.77 ± 3.88 μg/mL [DT], p =.023), whereas no significant difference was observed on cutoff day 6 (3.91 ± 2.60 vs. 4.40 ± 3.94 μg/mL, p =.465), suggesting that Cmin close to the steady‐state was achieved after day 5. DT causes a delay in achieving the therapeutic range. The hepatotoxicity rates were 21.5% and 36.8% in the RT and DT groups, respectively (p =.004); DT was an independent risk factor for hepatotoxicity. Conclusion: Although steady‐state concentrations may not be achieved by day 5, early dose optimisation using RT can prevent hepatotoxicity in Japanese patients. TDM should be performed on days 3–5 to ensure safety. However, subsequent TDM may be necessary due to a possible further increase in Cmin. [ABSTRACT FROM AUTHOR]

ε‐poly‐l‐lysine (ε‐PLL) is a natural polypeptide/polycation originating from bacteria. Thanks to its antifungal and antibacterial properties, it is the subject of extensive research in the food and medical industries. ε‐PLL is also used to develop biomaterials in a broad range of applications, such as drug delivery, wound healing, or antimicrobial coatings. Indeed, loading ε‐PLL inside nanoparticles, functionalizing implant surfaces with ε‐PLL, or developing hydrogels based on reactions between ε‐PLL and other polymers can improve the materials properties, leading to biocompatible, antibacterial, and antifungal systems. These characteristics are necessary not only for the development of biomaterials, for their integrity in a biological environment, but also for improving the performances of medical devices. Moreover, ε‐PLL can be used as an alternative to antibiotics as its mechanism of action reduces the bacterial resistance risk compared with antibiotics. Finally, "smart" systems using ε‐PLL may be developed, with controllable material degradation or drug delivery via pH or temperature variations. This review sought to gather the latest research on the development of antimicrobial biomaterials based on the ε‐PLL polypeptide. [ABSTRACT FROM AUTHOR]

A hypervalent iodine‐mediated bicyclization of N‐alkoxybenzamides for the synthesis of polyheterocycles is reported. Through metal‐free strategy, various N−O fused tetracyclic isoquinolones are synthesized in moderate to good yields at room temperature. The tetracyclic isoquinolones show good fluorescent properties, with maximum emission wavelength ranging from 442 to 459 nm. Notably, preliminary antifungal activity investigations indicate that N−O fused tetracyclic isoquinolones show good activities towards crop and forest pathogenic fungi. One of them exhibits 75.9 % antifungal activity towards C. chrysosperma, which is much better than the positive control. [ABSTRACT FROM AUTHOR]

BACKGROUND: Continuous use of synthetic bactericides and fungicides is causing pathogens to develop resistance, resulting in increased use of pesticides and affecting food security. The green pesticides derived from natural products could reduce or avoid 'pesticide hazards' caused by synthetic pesticides as a result of their unique mechanism of action. Therefore, it is of great significance to create green pesticides with novel structures. RESULTS: Herein, 30 novel myricetin derivatives containing piperidine and amide fragments were designed and synthesized using active group splicing. Among them, compound Z30 had excellent inhibitory effect against Xanthomonas oryzae pv. Oryzae (Xoo) with the half effective concentration (EC50) of 2.7 μg mL−1. Compound Z26 not only exhibited better antibacterial activity against Xaxonopodis pv. Citri (Xac) with EC50 of 3.9 μg mL−1, but also displayed higher antifungal activity against Rhizoctonia solani (Rs) with EC50 of 8.3 μg mL−1. In vivo experiments proved that Z30 against bacterial blight of rice and Z26 against rice blast exhibits significant protective and curative effect. Scanning electron microscopy (SEM) and transmission electron microscopy (TEM) showed that Z26 and Z30 could change the integrity of cell wall and membrane of pathogen Xoo, Xac and Rs, resulting in cytoplasmic leakage and eventually death. Enzymatic assay, molecular docking and molecular dynamics simulations (MDs) indicated that Z26 could be used as a potential succinate dehydrogenase inhibitor (SDHI). CONCLUSION: Z26 and Z30 significantly reduced the pathogenicity of the pathogens, which provided a new idea and direction for the development of green pesticides. © 2023 Society of Chemical Industry. [ABSTRACT FROM AUTHOR]

A new class of 3‐hydroxypyridine‐4‐one derivatives was synthesized and screened against several Gram‐positive and Gram‐negative bacteria, as well as two species of fungi. Among these synthesized compounds, the substituted derivatives with ortho‐ and para‐nitro and para‐methoxy groups showed the highest antibacterial activities against S. aureus and E. coli species with MIC value of 32 μg/mL, which were more potent compared to ampicillin as a reference drug. Furthermore, the substituted derivatives with ortho‐methoxy, ortho‐, para‐chloride, ortho‐, and para‐hydroxy groups exhibited MIC values of 64 μg/mL against S. aureus and E. coli species. In addition, the synthesized compounds were evaluated for their antifungal activities against C. albicans and A. niger strains. The best antifungal activity was observed for compounds with ortho‐methoxy, ortho‐hydroxy, and para‐methyl substitutions against A. niger species with MIC values of 64 μg/mL. The analysis of the antimicrobial results revealed that the type and position of the phenyl ring substituents greatly influence the antimicrobial activities of the synthesized compounds. Subsequently, molecular docking studies on E. coli species were performed to predict the interaction mode of these compounds in the active site of the receptor. Also, in silico ADME profile outputs showed that the compounds comply with the rule of five. [ABSTRACT FROM AUTHOR]

Summary: The co‐administration of venetoclax, a BCL‐2 inhibitor, with a mould‐active azole, such a posaconazole, has potential to both prevent invasive fungal infection (IFI) and reduce the required treatment dose, and cost, of venetoclax. Posaconazole drug‐level monitoring is critical to ensuring adequate mould prophylaxis. A retrospective audit of 99 patients at a tertiary cancer centre, with myeloid malignancies co‐prescribed venetoclax and posaconazole between January 2018 and April 2022, was undertaken to evaluate the adequacy of posaconazole prescribing and the rate of breakthrough IFI. Seventy‐six patients (77%) had at least one posaconazole level measured in the study period, with 37% requiring a dose adjustment based on steady‐state trough levels. Breakthrough IFI occurred in 4% of patients, typically within 1 month of commencing anti‐mould prophylaxis. Close monitoring of posaconazole levels in venetoclax‐treated patients, particularly in the early, outpatient setting, is critical. [ABSTRACT FROM AUTHOR]

This study was performed to explore the antifungal and antibiofilm effects of polyphyllin I (PPI) on Candida albicans. Microdilution assay was performed to determine the minimal inhibitory concentrations (MIC) of PPI against Candida species. Adhesion assay, hyphal growth assay, biofilm formation, and development were used to test the impacts of PPI on C. albicans virulence factors. Propidium iodide staining was performed to test whether the permeability of cell membrane was influenced by PPI. PPI showed significant antifungal activities against several Candida species, with MIC below or equal to 6.25 μM. PPI also inhibited the adhesion to polystyrene surfaces, hyphal growth, and biofilm formation. PPI significantly increased the permeability of C. albicans cell membrane. In sum, PPI can suppress the planktonic growth and biofilm of C. albicans and its mechanism involves the increased permeability of cell membrane. [ABSTRACT FROM AUTHOR]

The production of maize is limited by major diseases such as foliar blights, stalk rot, maydis leaf blight; banded leaf and sheath blight and many more. Synthesis of ecologically sustainable and naturally derived products can help us counter these diseases. Hence, Syringaldehyde (a natural occurring isolate) should explore as a viable option as green agrochemical. We performed a structure‐activity study to optimize syringaldehyde and its physicochemical properties. A series of novel syringaldehyde esters was synthesized and investigated focusing on esters' nature of lipophillicity, and membrane affinity. Tri‐chloro acetylated ester of syringaldehyde was emerged as broad‐spectrum fungicide. [ABSTRACT FROM AUTHOR]

BACKGROUND: Citrus canker and citrus blue mold are two severe diseases in citrus plants, which are mainly caused by Xanthomonas citri susp. citri (Xcc) and Penicillium italicum, respectively. The currently widely used pesticides for these two diseases are harmful to human health and the environment. Therefore, searching for novel antimicrobial agents, especially from natural resources, is getting increasing interest. RESULTS: In this study, the crude extract of Streptomyces sp. GLL‐9, an endophyte from a navel orange tree, was found to exhibit excellent antimicrobial effects against Xcc and P. italicum. Bioassay‐guided isolation led to the discovery of three actinomycins (Acts), actinomycin X2 (Act‐X2), actinomycin D (ActD), and actinomycin XOβ (Act‐XOβ). The MIC (minimum inhibitory concentration) values of Act‐X2, ActD, and Act‐XOβ were 31.25, 62.50, and 62.50 μg mL−1 against Xcc, respectively, while 62.50 (Act‐X2) and 125.00 μg mL−1 (ActD) against P. italicum, being better or comparable to the positive controls. The highest yield of Acts was obtained by solid‐state fermentation with rice containing 1% L‐tryptophan as a culture medium, being 6.03, 3.07, and 1.02 mg g−1, for Act‐X2, ActD, and Act‐XOβ, respectively. The ethyl acetate extract of Streptomyces sp. GLL‐9 cultivated under the optimal fermentation conditions (EAE‐1) can efficiently control these two citrus diseases by excessively producing reactive oxygen species (ROS) in both pathogens, damaging the cell membranes of P. italicum, and inhibiting the growth of Xcc. In addition, Act‐X2, ActD, and EAE‐1 displayed broad‐spectrum antifungal activity. CONCLUSION: EAE‐1 and Acts produced by Streptomyces sp. GLL‐9 have high potential as novel antimicrobial agents against plant pathogens. © 2023 Society of Chemical Industry. [ABSTRACT FROM AUTHOR]

In this study aimed to the synthesis of novel bis‐nicotinonitrile derivatives starting from 1,3‐bis‐chalcones and investigate their antimicrobial activity potentials. Bis‐nicotinonitrile derivatives were synthesized from 1,3‐bis‐chalcone derivatives reacted with malononitrile in ethanol in the presence of potassium carbonate. Characterization of the obtained compounds was carried out by spectroscopic methods. In total, 12 new 1,3‐phenylene‐bis‐nicotinonitrile derivatives were synthesized. Finally, the antimicrobial and antibiofilm activities of synthesized 1,3‐phenylene‐bis‐nicotinonitrile derivatives were tested against 5 microorganisms. As a result, it was observed that the synthesized new nicotinonitrile derivatives were quite active especially in terms of antibiofilm activity. [ABSTRACT FROM AUTHOR]

Sporotrichosis caused by Sporothrix brasiliensis is a global emergent infectious disease. Due to the scarcity of therapeutic options for fungal diseases, new antifungals are urgently needed. Nikkomycin Z (NikZ) is a future option as an agent against dimorphic fungi. We evaluated NikZ monotherapy and in combination with itraconazole (ITZ; the conventional therapy) in the treatment of experimental sporotrichosis caused by S. brasiliensis in a murine model. Animals were subcutaneously infected, and treated orally for 30 days. The study groups were as follows control (untreated), ITZ group (50 mg/kg/day), and three groups treated with NikZ, two by monotherapy (200 or 400 mg/kg/day), and one combining NikZ (400 mg/kg/day) and ITZ. Efficacy of treatments was evaluated via body weight gain, mortality and fungal burden in tissues. Efficacy was noted in all treatment groups, and the group receiving the drug combination showed even better results than those with monotherapy. Our study shows for the first time the high potential of NikZ to be used in the treatment of sporotrichosis caused by S. brasiliensis. [ABSTRACT FROM AUTHOR]

Multidrug resistance (MDR) causes difficulties in the treatment of infections and cancer. Research and development studies have become increasingly important for the strategy of preventing MDR. There is a need for new multitarget drug research and advancement to reduce the development of drug resistance in drug‐drug interactions and reduce cost and toxic effects. This study aimed to determine the effects of multi‐target triazene compounds on antibacterial, antifungal, antiviral, cytotoxic, and larvicidal activities were investigated in vitro. A series of 12 novel of 1,3‐diaryltriazene‐substituted sulfadiazine (SDZ) derivatives were synthesized, and the obtained pure products characterized in detail by spectroscopic and analytic methods (FT‐IR, 1H‐NMR, 13C‐NMR, and melting points). The antibacterial and antifungal activities of these derivatives (AH1‐12) were determined by broth microdilution method. All derivatives have been evaluated in cell‐based assays for cytotoxic and antiviral activities against Modified Vaccinia Virus Ankara. The larvicidal efficacy of these chemical compounds was also investigated by using Lucilia sericata (L. sericata) larvae. Twelve 1,3‐diaryltriazene‐substituted SDZ derivatives (AH1‐12) were designed and developed as potent multitargeted compounds. Among them, the AH1 derivative showed the most antibacterial and antifungal activity. Besides, synthesized derivatives AH2, AH3, AH5, and AH7 showed higher antiviral activity than SDZ. All synthesized derivatives showed higher cytotoxic activity than SDZ. Also, they showed larvicidal activity at 72 h of the experiment. As a result, these compounds might be great leads for the development of next‐generation multitargeted agents. [ABSTRACT FROM AUTHOR]

Due to the increasing demand for novel antimicrobials agents to treat microbial infections, the current work, focused on the synthesis of new agents owing innovative chemistry and modes of action. We describe an organic‐inorganic hybrid compound with the formula (C8H14N2)4[(FeCl6)(FeCl4)]Cl4, it was synthesized via slow evaporation at room temperature, and characterized using various techniques. The compound crystallizes in the tetragonal system, with I41/a space group. In the crystal structure, the organic layers are made up of protonated m‐Xylylene diamine (C8H14N2)2+ creating between them free tunnels, in which inorganic entities can be placed. These entities contain one octahedral (FeCl6)3− ion, one tetrahedral (FeCl4)−, and uncoordinated chlorine anions. Crystal cohesion is achieved through N−H...Cl hydrogen bonds and Cl...Cl interactions. The UV‐vis spectroscopy was investigated and the optical band gap energy 2.00 eV suggests the semiconductor behavior of the title compound. The functional groups present in the crystal structure were performed by FTIR spectroscopy. Thermal analysis was also carried out. Analysis of the Hirshfeld surface revealed that the H...Cl/Cl...H interactions dominate the structure (74 %). The new Fe(III) complex gave strong antibacterial potential against S. aureus, E. coli, M. luteus, it was able to inhibit growth of Candida species and Trichophyton intergiditale and showing lysozyme activity. [ABSTRACT FROM AUTHOR]

Haloferax mediterranei archaea has been utilized to biosynthesize Poly(3‐hydroxybutyrate‐co‐3‐hydroxyvalerate) (PHBV) polyester from date waste as carbon source. The produced biopolymer has been composited with different percentages (1 %, 3 %, 5 % and 10 %) of a hybrid filler based on 1 : 1 carboxylated multi‐walled carbon nanotubes (CMWCNTs) and graphene nanoplates (GNPts). The synthesized bionanocomposites PHBV/(CMWCNTs‐GNPts)(1,3,5,10%) have been characterized by FTIR, TGA, XRD, SEM and EDX. In addition, they were studied for their antibacterial properties against gram negative and gram positive strains of M. Luteus, S. Aureus, P. Aerugensa and E. Coli, and the results showed excellent antibacterial effect especially against gram negative strains of P. Aerugensa and E. Coli, showing inhibition zones of 52 % and 81 %, respectively, compared to chloramphenicol control that is used. Also, antifungal activities were investigated against G. Candidum and C. Albicans and showed that the produced bionanocomposites had inhibition zones of 32 % and 73 %, respectively, compared to the antifungal drug clotrimazole which was used as control. [ABSTRACT FROM AUTHOR]

The present study reports the green synthesis of cupric oxide nanoparticles (CuO NPs) by an aqueous leaf extract of Moringa oleifera and the antifungal activity assessment of CuO NPs against the phytopathogenic fungi Aspergillus flavus and Aspergillus niger. The CuO NPs showed variable fungitoxic effects against A. flavus and A. niger. At higher doses (1 mg/mL), 83.51 % of mycelial inhibition was found against A. flavus, but 43.51 % was found against A. niger. The percentage inhibition of mycelial growth was found to be dose dependent. The cell viability analysis was carried out to reveal the mechanism of the fungitoxic effect of synthesized NPs and it was revealed that the CuO NPs caused oxidative stress associated with increased ROS production, leading to fungal cell death. The synthesized CuO NPs showed single phase cupric oxide with a monoclinic structure and highly uniform in size (3–5 nm). As the synthesized CuO NPs showed good stability under open atmospheric conditions and a fungitoxicity effect against A. flavus, they may be used to control fungal diseases in an eco‐friendly manner. [ABSTRACT FROM AUTHOR]