Design and synthesis of bis(indolyl)-hydrazide-hydrazone derivatives and their antifungal activities against plant pathogen fungi.

A series of bis(indolyl)-hydrazide-hydrazone derivatives were synthesised, and their structures were characterised using 1H-NMR and HRMS. The antifungal activity of the prepared compounds was evaluated against Pyricularia oryzae Cav., Colletotrichum -gloeosporioides Penz., Botrytis cinerea Pers.: Fr. and Rhizoctonia solani Kühn using the mycelial growth rate method. The preliminary bioassays revealed that most of the synthesised compounds exhibited antifungal activity against the four tested fungi and displayed a remarkable inhibitory effect on the mycelium growth of R. solani. In particular, compounds 3b, 3c, and 3k demonstrated significant antifungal activity against R. solani, with EC50 values of 26.42, 20.74, and 22.41 µM, respectively, outperforming the positive control shenqinmycin (47.18 µM) and carvacrol (49.13 µM).

O-carboxymethyl chitosan in biomedicine: A review.

O-carboxymethyl chitosan (O-CMC) is a chitosan derivative produced through the substitution of hydroxyl (-OH) functional groups in glucosamine units with carboxymethyl (-CH2COOH) substituents, effectively addressing the inherent solubility issues of chitosan in aqueous solutions. O-CMC has garnered significant interest due to its enhanced solubility, elevated viscosity, minimal toxicity, and advantageous biocompatibility properties. Furthermore, O-CMC demonstrates antibacterial, antifungal, and antioxidant characteristics, rendering it a promising candidate for various biomedical uses such as wound healing, tissue engineering, anti-tumor therapies, biosensors, and bioimaging. Additionally, O-CMC is well-suited for the fabrication of nanoparticles, hydrogels, films, microcapsules, and tablets, offering opportunities for effective drug delivery systems. This review outlines the distinctive features of O-CMC, offers analyses of advancements and future potential based on current research, examines significant obstacles for clinical implementation, and foresees its ongoing significant impacts in the realm of biomedicine.

Bioassay-guided isolation of three new alkaloids from Suillus bovinus and preliminary mechanism against ginseng root rot.

In order to control the occurrence of ginseng root rot caused by Fusarium solani (Mart.) Sacc., the antifungal compounds of the mushroom Suillus bovinus were investigated. And three new alkaloids (1-3), named bovinalkaloid A-C, along with one known analog (4), were isolated and identified by bioassay-guided isolation and spectroscopic analyses. Compound 1 strongly inhibited the mycelial growth and spore germination of F. solani with minimum inhibitory concentration of 2.08 mM. Increases in electrical conductivity, nucleic acid, and protein contents, and decreases in lipid content showed that the membrane permeability and integrity were damaged by compound 1. Compound 1 also increased the contents of malondialdehyde and hydrogen peroxide and the activities of antioxidant enzymes, indicating that lipid peroxidation had taken place in F. solani. Compound 1 may serve as a natural alternative to synthetic fungicides for the control of ginseng root rot.

A sustainable green-approach for biofabrication of chitosan nanoparticles, optimization, characterization, its antifungal activity against phytopathogenic Fusarium culmorum and antitumor activity.

Chitosan is a natural non-toxic, biocompatible, biodegradable, and mucoadhesive polymer. It also has a broad spectrum of applications such as agriculture, medical fields, cosmetics and food industries. In this investigation, chitosan nanoparticles were produced by an aqueous extract of Cympopogon citratus leaves as a reducing agent. According to the SEM and TEM micrographs, CNPs had a spherical shape, and size ranging from 8.08 to 12.01 nm. CNPs have a positively charged surface with a Zeta potential of + 26 mV. The crystalline feature of CNPs is determined by X-ray diffraction. There are many functional groups, including C꞊C, CH2-OH, C-O, C-S, N-H, CN, CH and OH were detected by FTIR analysis. As shown by the thermogravimetric study, CNPs have a high thermal stability. For the optimization of the green synthesis of CNPs, a Face centered central composite design (FCCCD) with 30 trials was used. The maximum yield of CNPs (13.99 mg CNPs/mL) was produced with chitosan concentration 1.5%, pH 4.5 at 40 °C, and incubation period of 30 min. The antifungal activity of CNPs was evaluated against phytopathogenic fungus; Fusarium culmorum. A 100% rate of mycelial growth inhibition was gained by the application of 20 mg CNPs/mL. The antitumor activity of the green synthesized CNPs was examined using 6 different cell lines, the viability of the cells reduced when the concentration of green synthesized CNPs increased, the IC50 dose of the green synthesized CNPs on the examined cell lines HePG-2, MCF-7, HCT-116, PC-3, Hela and WI-38 was 36.25 ± 2.3, 31.21 ± 2.2, 67.45 ± 3.5, 56.30 ± 3.3, 44.62 ± 2.6 and 74.90 ± 3.8; respectively.

The potent effect of selenium nanoparticles: insight into the antifungal activity and preservation of postharvest strawberries from gray mold diseases.

BACKGROUND: Most microorganisms that cause food decay and the lower the shelf life of foods are fungi. Nanotechnologies can combat various diseases and deal with the application of nanomaterial to target cells or tissues. In this study selenium nanoparticles (Se-NPs) were synthesized using ascorbic acid and characterized by ultraviolet-visible spectroscopy, transmission electron microscopy (TEM), X-ray diffraction and zeta potential. The different concentrations of As/Se-NPs were tested against various fungi, including Alternaria linicola, Alternaria padwickii, Botrytis cinerea, Bipolaris sp., Cephalosporium acremonium, Fusarium moniliform and Fusarium semitectum. This study tested the influence of coated As/Se-NPs on healthy strawberry fruits and those infected with Botrytis cinerea during 16 days of storage, with regard to shelf life, decay percentage, weight loss, total titratable acidity percentage, total soluble solids content (TSS) and anthocyanin content. RESULTS: Energy-dispersive X-ray analysis showed only two elements: selenium and oxygen. TEM images showed that the nanoparticles ranged in size between 26 to 39 nm and were rhombohedral in shape. Se-NPs showed antifungal activity against all tested fungi, the most effective being against Botrytis cinerea, Cephalosporium acremonium and Fusarium semitectum. During storage periods of strawberries fruits coated with As/Se-NPs, the shelf life was increased, and the number of decaying fruits was less than in control (uncoated) and coated infected fruits. The decline in weight loss was lower in coated fruits than in control fruits. CONCLUSION: These findings demonstrated that As/Se-NPs could effectively maintain the postharvest quality of strawberries, even when the fruit was infected with B. cinerea. © 2024 Society of Chemical Industry.

Novel Pyrazole-4-Carboxamide Derivatives Containing Oxime Ether Group as Potential SDHIs to Control Rhizoctonia solani.

In the search for novel succinate dehydrogenase inhibitor (SDHI) fungicides to control Rhizoctonia solani, thirty-five novel pyrazole-4-carboxamides bearing either an oxime ether or an oxime ester group were designed and prepared based on the strategy of molecular hybridization, and their antifungal activities against five plant pathogenic fungi were also investigated. The results indicated that the majority of the compounds containing oxime ether demonstrated outstanding in vitro antifungal activity against R. solani, and some compounds also displayed pronounced antifungal activities against Sclerotinia sclerotiorum and Botrytis cinerea. Particularly, compound 5e exhibited the most promising antifungal activity against R. solani with an EC50 value of 0.039 µg/mL, which was about 20-fold better than that of boscalid (EC50 = 0.799 µg/mL) and 4-fold more potent than fluxapyroxad (EC50 = 0.131 µg/mL). Moreover, the results of the detached leaf assay showed that compound 5e could suppress the growth of R. solani in rice leaves with significant protective efficacies (86.8%) at 100 µg/mL, superior to boscalid (68.1%) and fluxapyroxad (80.6%), indicating promising application prospects. In addition, the succinate dehydrogenase (SDH) enzymatic inhibition assay revealed that compound 5e generated remarkable SDH inhibition (IC50 = 2.04 µM), which was obviously more potent than those of boscalid (IC50 = 7.92 µM) and fluxapyroxad (IC50 = 6.15 µM). Furthermore, SEM analysis showed that compound 5e caused a remarkable disruption to the characteristic structure and morphology of R. solani hyphae, resulting in significant damage. The molecular docking analysis demonstrated that compound 5e could fit into the identical binding pocket of SDH through hydrogen bond interactions as well as fluxapyroxad, indicating that they had a similar antifungal mechanism. The density functional theory and electrostatic potential calculations provided useful information regarding electron distribution and electron transfer, which contributed to understanding the structural features and antifungal mechanism of the lead compound. These findings suggested that compound 5e could be a promising candidate for SDHI fungicides to control R. solani, warranting further investigation.

Antipathogenic Activities of Volatile Organic Compounds Produced by Bacillus velezensis LT1 against Sclerotium rolfsii LC1, the Pathogen of Southern Blight in Coptis chinensis.

This study explores the antipathogenic properties of volatile organic compounds (VOCs) produced by Bacillus velezensis LT1, isolated from the rhizosphere soil of Coptis chinensis. The impact of these VOCs on the mycelial growth of Sclerotium rolfsii LC1, the causative agent of southern blight in C. chinensis, was evaluated using a double Petri-dish assay. The biocontrol efficacy of these VOCs was further assessed through leaf inoculation and pot experiments. Antifungal VOCs were collected using headspace solid-phase microextraction (SPME), and their components were identified via gas chromatography-mass spectrometry (GC-MS). The results revealed that the VOCs significantly inhibited the mycelial growth and sclerotia germination of S. rolfsii LC1 and disrupted the morphological integrity of fungal mycelia. Under the influence of these VOCs, genes associated with chitin synthesis were upregulated, while those related to cell wall degrading enzymes were downregulated. Notably, 2-dodecanone and 2-undecanone exhibited inhibition rates of 81.67% and 80.08%, respectively. This research provides a novel approach for the prevention and management of southern blight in C. chinensis, highlighting the potential of microbial VOCs in biocontrol strategies.

Biocontrol activity of an endophytic Alternaria alternata Aa-Lcht against apple Valsa canker.

Apple Valsa canker (AVC), caused by Valsa mali, is the most serious branch disease for apples in East Asia. Biocontrol constitutes a desirable alternative strategy to alleviate the problems of orchard environment pollution and pathogen resistance risk. It is particularly important to explore efficient biocontrol microorganism resources to develop new biocontrol technologies and products. In this study, an endophytic fungus, which results in the specific inhibition of the growth of V. mali, was isolated from the twig tissue of Malus micromalus with a good tolerance to AVC. The fungus was identified as Alternaria alternata, based on morphological observations and phylogenetic analysis, and was named Aa-Lcht. Aa-Lcht showed a strong preventive effect against AVC, as determined with an in vitro twig evaluation method. When V. mali was inhibited by Aa-Lcht, according to morphological and cytological observations, the hyphae was deformed and it had more branches, a degradation in protoplasm, breakages in cell walls, and then finally died completely due to mycelium cells. Transcriptome analysis indicated that Aa-Lcht could suppress the growth of V. mali by inhibiting the activity of various hydrolases, destroying carbohydrate metabolic processes, and damaging the pathogen membrane system. It was further demonstrated that Aa-Lcht could colonize apple twig tissues without damaging the tissue's integrity. More importantly, Aa-Lcht could also stimulate the up-regulated expression of defense-related genes in apples together with the accumulation of reactive oxygen species and callose deposition in apple leaf cells. Summarizing the above, one endophytic biocontrol resource was isolated, and it can colonize apple twig tissue and play a biocontrol role through both pathogen inhibition and resistance inducement.

Aloperine-Type Alkaloids with Antiviral and Antifungal Activities from the Seeds of Sophora alopecuroides L.

As a continuous flow investigation of novel pesticides from natural quinolizidine alkaloids, the chemical compositions of the seeds of Sophora alopecuroides were thoroughly researched. Fifteen new aloperine-type alkaloids (1-15) as well as six known aloperine-type alkaloids (16-21) were obtained from the extract of S. alopecuroides. The structures of 1-21 were confirmed via HRESIMS, NMR, UV, IR, ECD calculations, and X-ray diffraction. The antiviral activities of 1-21 against tobacco mosaic virus (TMV) were detected following the improved method of half-leaf. Compared with ningnanmycin (protective: 69.7% and curative: 64.3%), 15 exhibited excellent protective (71.7%) and curative (64.6%) activities against TMV. Further biological studies illustrated that 15 significantly inhibited the transcription of the TMV-CP gene and increased the activities of polyphenol oxidase (PPO), peroxidase (POD), superoxide dismutase (SOD), and phenylalanine ammonia-lyase (PAL). The antifungal activities of 1-21 against Phytophythora capsica, Botrytis cinerea, Alternaria alternata, and Gibberella zeae were screened according to a mycelial inhibition test. Compound 13 displayed excellent antifungal activity against B. cinerea (EC50: 7.38 µg/mL). Moreover, in vitro antifungal mechanism studies displayed that 13 causes accumulation of reactive oxygen species and finally leads to mycelia cell membrane damage and cell death in vitro.

Green synthesis of silver and gold nanoparticles in Callistemon viminalis extracts and their antimicrobial activities.

In the current study, the bottlebrush [Callistemon viminalis (Sol. ex Gaertn.) G. Don] plant was selected for the green synthesis of silver (Ag) and gold (Au) nanoparticles and to evaluate its antibacterial and antifungal activities. Phytochemical screening of C. viminalis confirmed the presence of alkaloids, anthraquinones, saponins, tannins, betacyanins, phlobatanins, coumarins, terpenoids, steroids, glycosides, and proteins. To characterize the synthesized Ag and Au NPs, UV-Visible spectroscopy, FTIR spectroscopy for functional group identification, field emission scanning electron microscopy (FE-SEM) for particle size, and elemental analysis were performed using EDX. The UV-Visible absorption spectra of the green-synthesized Ag and Au nanoparticles were found to have a maximum absorption band at 420 nm for Ag NPs and 525 nm for Au NPs. FE-SEM analysis of the synthesized NPs revealed a circular shape with a size of 100 nm. Elemental analysis was performed for the synthesis of Ag and Au NPs, which confirmed the purity of the nanoparticles. The greenly synthesized Ag and Au NPs were also evaluated for their anti-bacterial and anti-fungal activities, which exhibited prominent inhibition activities against Escherichia coli, Staphylococcus aureus, Klebsiella pneumoniae, Pseudomonas aeruginosa, Candida albicans, C. krusei, Aspergillus sp., and Trichoderma species. The highest zone of inhibition 15.5 ± 0.75 and 15 ± 0.85 mm was observed for Ag NPs against E. coli and P. aeruginosa. Similarly, Trichoderma sp. and Aspergillus sp. were inhibited by Ag NPs up to 13.5 ± 0.95 and 13 ± 0.70 mm. This work will open doors for the development of new antimicrobial agents using green chemistry.

Isolating Antipathogenic Fungal Coumarins from Coriaria nepalensis and Determining Their Primary Mechanism In Vitro.

Through bioassay-guided isolation, eight undescribed coumarins (1-8), along with six reported coumarins (9-14), were obtained from Coriaria nepalensis. The new structures were determined by using IR, UV, NMR, HRESIMS, and ECD calculations. The results of the biological activity assays showed that compound 9 exhibited broad spectrum antifungal activities against all tested fungi in vitro and a significant inhibitory effect on Phytophthora nicotianae with an EC50 value of 3.00 µg/mL. Notably, compound 9 demonstrated greater curative and protective effects against tobacco balack shank than those of osthol in vivo. Thus, 9 was structurally modified to obtain new promising antifungal agents, and the novel derivatives (17b, 17j, and 17k) exhibited better effects on Sclerotinia sclerotiorum than did lead compound 9. Preliminary mechanistic exploration illustrated that 9 could enhance cell membrane permeability, destroy the morphology and ultrastructure of cells, and reduce the exopolysaccharide content of P. nicotianae mycelia. Furthermore, the cytotoxicity results revealed that compound 9 exhibited relatively low cytotoxicity against HEK293 cell lines with an inhibition rate of 33.54% at 30 µg/mL. This research is promising for the discovery of new fungicides from natural coumarins with satisfactory ecological compatibility.

Evaluation of the antifungal properties of nanoliposomes containing rhinacanthin-C isolated from the leaves of Rhinacanthus nasutus.

Fungal infections represent a challenging threat to the human health. Microsporum gypseum and Trichophyton rubrum are pathogenic fungi causing various topical mycoses in humans. The globally emerging issue of resistance to fungi demands the development of novel therapeutic strategies. In this context, the application of nanoliposomes as vehicles for carrying active therapeutic agents can be a suitable alternative. In this study, rhinacanthin-C was isolated from Rhinacanthus naustus and encapsulated in nano-liposomal formulations, which were prepared by the modified ethanol injection method. The two best formulations composed of soybean phosphatidylcholine (SPC), cholesterol (CHL), and tween 80 (T80) in a molar ratio of 1:1:0 (F1) and 1:1:0.5 (F2) were proceeded for experimentation. The physical characteristics and antifungal activities were performed and compared with solutions of rhinacanthin-C. The rhinacanthin-C encapsulating efficiencies in F1 and F2 were 94.69 ± 1.20% and 84.94 ± 1.32%, respectively. The particle sizes were found to be about 221.4 ± 13.76 nm (F1) and 115.8 ± 23.33 nm (F2), and zeta potential values of -38.16 mV (F1) and -40.98 mV (F2). Similarly, the stability studies of rhinacanthin-C in liposomes demonstrated that rhinacanthin-C in both formulations was more stable in mediums with pH of 4.0 and 6.6 than pure rhinacanthin-C when stored at the same conditions. Rhinacanthin-C in F1 was slightly more stable than F2 when stored in mediums with a pH of 10.0 after three months of storage. However, rhinacanthin-C in both formulations was less stable than pure rhinacanthin-C in a basic medium of pH 10.0. The antifungal potential was evaluated against M. gypsum and T. rubrum. The findings revealed a comparatively higher zone of inhibition for F1. In the MIC study, SPC: CHL: T80 showed higher inhibition against M. gypseum and a slightly higher inhibition against T. rubrum compared to free rhinacanthin-C solution. Moreover, rhinacanthin-C showed significant interaction against 14α-demethylase in in silico study. Overall, this study demonstrates that nanoliposomes containing rhinacanthin-C can improve the stability and antifungal potential of rhinacanthin-C with sustained and prolonged duration of action and could be a promising vehicle for delivery of active ingredients for targeting various fungal infections.

Four unreported aporphine alkaloids with antifungal activities from Artabotrys hexapetalus.

In this study, the extract from Artabotrys hexapetalus showed strong antifungal activity against phytopathogenic fungi in vitro. Four unreported aporphine alkaloids, hexapetalusine A-D (1-4), were isolated from stems and roots of Artabotrys hexapetalus (L.f.) Bhandari, along with six known aporphine alkaloids (5-10). Their chemical structures were elucidated by extensive spectroscopic analysis. The absolute configurations of 1-3 were determined using single-crystal X-ray diffractions and ECD calculations. Hexapetalusine A-C (1-3) were special amidic isomers. Additionally, all isolated compounds were evaluated for their antifungal activity against four phytopathogenic fungi in vitro. Hexapetalusine D (4) exhibited weak antifungal activity against Curvularia lunata. Liriodenine (5) displayed significant antifungal activity against Fusarium proliferatum and Fusarium oxysporum f. sp. vasinfectum, which is obviously better than positive control nystatin, suggesting that it had great potential to be developed into an effective and eco-friendly fungicide.

New polyketides from the starfish-derived symbiotic fungus Penicillium sp. GGF16-1-2.

One new rare carbon-bridged citrinin dimer quinocitrindimer C (1) as a pair of epimers, two new polyketide penicilliodes D (3) and E (4) together with nine known citrinin derivatives, were isolated from the fermentation broth of starfish-derived symbiotic fungus Penicillium sp. GGF16-1-2. Their structures and configurations were elucidated by comprehensively spectroscopic data analysis and electronic circular dichroism calculations. Eleven citrinin derivatives were tested by Colletotrichum gloeosporioides, and compound 2 played a significant antifungal activity against Colletotrichum gloeosporioides with LC50 value of 0.27 µg/ml.

Isolation and Characterization of Antimicrobial Metabolites from the Sophora tonkinensis-Associated Fungus Penicillium sp. GDGJ-N37.

Chemical investigation of Penicillium sp. GDGJ-N37, a Sophora tonkinensis-associated fungus, yielded two new azaphilone derivatives, N-isoamylsclerotiorinamine (1) and 7-methoxyl-N-isoamylsclerotiorinamine (2), and four known azaphilones (3-6), together with two new chromone derivatives, penithochromones X and Y (7 and 8). Their structures were elucidated based on spectroscopic data, CD spectrum, and semi-synthesis. Sclerotioramine (3) showed significant antibacterial activities against B. subtilis and S. dysentery, and it also showed most potent anti-plant pathogenic fungi activities against P. theae, C. miyabeanus, and E. turcicum.

Bacillus velezensis BVE7 as a promising agent for biocontrol of soybean root rot caused by Fusarium oxysporum.

Introduction: Soybean root rot (SRR), caused by Fusarium oxysporum, is a severe soil-borne disease in soybean production worldwide, which adversely impacts the yield and quality of soybean. The most effective method for managing crop soil-borne diseases and decreasing reliance on chemical fungicides, such as Bacillus spp., is via microbial biocontrol agents. Methods and Results: In this study, a soil-isolated strain BVE7 was identified as B. velezensis, exhibiting broad-spectrum activity against various pathogens causing soybean root rot. BVE7 sterile filtrate, at a concentration of 10%, demonstrated significant antifungal activity by inhibiting the conidial germination, production, and mycelial growth of F. oxysporum by 61.11%, 73.44%, and 85.42%, respectively, causing hyphal malformations. The antifungal compound produced by BVE7 demonstrated adaptability to a standard environment. The pot experiment showed that BVE7 suspension could effectively control soybean root rot, with the highest control efficiency of 75.13%. Furthermore, it considerably enhanced the activity of catalase, phenylalanine ammonia lyase, superoxide dismutase, and peroxidase in soybean roots, while also preventing an increase in malondialdehyde activity. By improving the host resistance towards pathogens, the damage caused by fungi and the severity of soybean root rot have been reduced. Discussion: This study presents the innovative utilization of B. velezensis, isolated from soybean roots in cold conditions, for effectively controlling soybean root rot caused by F. oxysporum. The findings highlight the remarkable regional and adaptive characteristics of this strain, making it an excellent candidate for combating soybean root rot in diverse environments. In conclusion, B. velezensis BVE7 demonstrated potential in effectively reducing SRR incidence and can be considered as a viable option for SRR management.

Discovery of Highly Efficient Novel Antifungal Lead Compounds Targeting Succinate Dehydrogenase: Pyrazole-4-carboxamide Derivatives with an N-Phenyl Substituted Amide Fragment.

Developing environmentally friendly fungicides is crucial to tackle the issue of rising pesticide resistance. In this study, a series of novel pyrazole-4-carboxamide derivatives containing N-phenyl substituted amide fragments were designed and synthesized. The structures of target compounds were confirmed by 1H NMR, 13C NMR, and HRMS, and the crystal structure of the most active compound N-(1-(4-(4-(tert-butyl)benzamido)phenyl)propan-2-yl)-3-(difluoromethyl)-N-methoxy-1-methyl-1H-pyrazole-4-carboxamide (U22) was further determined by X-ray single-crystal diffraction. The bioassay results indicated that the 26 target compounds possessed good in vitro antifungal activity against Sclerotinia sclerotiorum with EC50 values for compounds U12, U13, U15, U16, U18, U22, and U23 being 4.17 ± 0.46, 8.04 ± 0.71, 7.01 ± 0.71, 12.77 ± 1.00, 8.11 ± 0.70, 0.94 ± 0.11, and 9.48 ± 0.83 µg·mL-1, respectively, which were the similar to controls bixafen (6.70 ± 0.47 µg·mL-1), fluxapyroxad (0.71 ± 0.14 µg·mL-1), and pydiflumetofen (0.06 ± 0.01 µg·mL-1). Furthermore, in vivo antifungal activity results against S. sclerotiorum indicated that compounds U12 (80.6%) and U22 (89.9%) possessed excellent preventative efficacy at 200 µg·mL-1, which was the same as the control pydiflumetofen (82.4%). Scanning electron microscopy and transmission electron microscopy studies found that the compound U22 could destroy the hyphal morphology and damage mitochondria, cell membranes, and vacuoles. The results of molecular docking of compound U22 and pydiflumetofen with succinate dehydrogenase (SDH) indicated they interact well with the active site of SDH. This study validated our approach and design strategy to produce compounds with an enhanced biological activity as compared to the parent structure.

Design, Synthesis, and Antifungal Activity of Novel 2-Ar-1,2,3-Triazole Derivatives.

Triazoles are crucial molecular frameworks in the development of fungicidal compounds. Although there has been extensive research on triazole derivatives for fungicide discovery, the investigation of 2-Ar-substituted-1,2,3-triazoles remains in progress. This study reports the synthesis and evaluation of the fungicidal activity of 27 distinct 2-Ar-substituted-1,2,3-triazole derivatives. These derivatives were synthesized from anilines through a three-step process, with the key step being the Cu(II)-catalyzed annulation reaction of readily accessible alkyl 3-aminoacrylates with aryldiazonium salts. All derivatives were novel, and their structures were characterized using 1H NMR, 13C NMR, and high-resolution mass spectrometry. Their antifungal activity was tested against five phytopathogenic fungi. Twelve of the target compounds exhibited better performance than the positive control hymexazol in the fungal test. Notably, compound 6d demonstrated the most potent inhibition against Botryosphaeria dothidea with an EC50 value of 0.90 mg/L. The structure-activity relationships are also discussed in this paper. Preliminary studies on the antifungal mechanism of compound 6d revealed that it inhibits ergosterol synthesis and alters the morphology and ultrastructure of the B. dothidea mycelium. These results suggest that the designed 2-Ar-substituted-1,2,3-triazole-containing hydrazone derivatives warrant further investigation as potential lead compounds for novel antifungal agents.

Synthesis, in silico and in vitro antimicrobial efficacy of substituted arylidene-based quinazolin-4(3H)-one motifs.

Introduction: Quinazolin-4(3H)-one derivatives have attracted considerable attention in the pharmacological profiling of therapeutic drug targets. The present article reveals the development of arylidene-based quinazolin-4(3H)-one motifs as potential antimicrobial drug candidates. Methods: The synthetic pathway was initiated through thermal cyclization of acetic anhydride on anthranilic acid to produce 2-methyl-4H-3,1-benzoxazan-4-one 1, which (upon condensation with hydrazine hydrate) gave 3-amino-2-methylquinazolin-4(3H)-one 2. The reaction of intermediate 2 at its amino side arm with various benzaldehyde derivatives furnished the final products, in the form of substituted benzylidene-based quinazolin-4(3H)-one motifs 3a-l, and with thiophene-2-carbaldehyde to afford 3 m. The purified targeted products 3a-m were effectively characterized for structural authentication using physicochemical parameters, microanalytical data, and spectroscopic methods, including IR, UV, and 1H- and 13C-NMR, as well as mass spectral data. The substituted arylidene-based quinazolin-4(3H)-one motifs 3a-m were screened for both in silico and in vitro antimicrobial properties against selected bacteria and fungi. The in silico studies carried out consisted of predicted ADMET screening, molecular docking, and molecular dynamics (MD) simulation studies. Furthermore, in vitro experimental validation was performed using the agar diffusion method, and the standard antibacterial and antifungal drugs used were gentamicin and ketoconazole, respectively. Results and discussion: Most of the compounds possessed good binding affinities according to the molecular docking studies, while MD simulation revealed their levels of structural stability in the protein-ligand complexes. 2-methyl-3-((thiophen-2-ylmethylene)amino) quinazolin-4(3H)-one 3 m emerged as both the most active antibacterial agent (with an minimum inhibitory concentration (MIC) value of 1.95 µg/mL) against Staphylococcus aureus and the most active antifungal agent (with an MIC value of 3.90 µg/mL) against Candida albicans, Aspergillus niger, and Rhizopus nigricans.

Antiviral and antimicrobial applications of chalcones and their derivatives: From nature to greener synthesis.

Chalcones and their derivatives have been widely studied due to their versatile pharmacological and biological activities, such as anti-inflammatory, antibacterial, antiviral, and antitumor effects. These compounds have shown suitable antiviral effects through the selective targeting of a variety of viral enzymes, including lactate dehydrogenase, glyceraldehyde-3-phosphate dehydrogenase (GAPDH), fumarate reductase, protein tyrosine phosphatase, topoisomerase-II, protein kinases, integrase/protease, and lactate/isocitrate dehydrogenase, among others. Chalcones and their derivatives have displayed excellent potential for combating pathogenic bacteria and fungi (especially, multidrug-resistant bacteria). However, relevant mechanisms should be further explored, focusing on inhibitory effects against DNA gyrase B, UDP-N-acetylglucosamine enolpyruvyl transferase (MurA), and efflux pumps (e.g., NorA), among others. In addition, the antifungal and antiparasitic activities of these compounds (e.g., antitrypanosomal and antileishmanial properties) have prompted additional explorations. Nonetheless, systematic analysis of the relevant mechanisms, biosafety issues, and pharmacological properties, as well as clinical translation studies, are vital for practical applications. Herein, recent advancements pertaining to the antibacterial, antiviral, antiparasitic, and antifungal activities of chalcones and their derivatives are deliberated, focusing on the relevant mechanisms of action, crucial challenges, and future prospects. Furthermore, due to the great importance of greener and more sustainable synthesis of these valuable compounds, especially on an industrial scale, the progress made in this field has been briefly discussed. Hopefully, this review can serve as a catalyst for researchers to delve deeper into the exploration and designing of novel chalcone compounds with medicinal properties, especially against pathogenic viruses and multidrug-resistant bacteria as major causes of concern for human health.