Promising Antifungal Activity Research Articles

Evaluation of structural parameters of monoclinic nanocrystalline CuO and study of sunlight-driven photocatalytic dye degradation, antimicrobial and antioxidant potential

Highly pure, crystalline and spherical-shaped Copper oxide nanoparticles (NPs) have been synthesized via facile chemical coprecipitation. Various models including the Scherrer, Monshi-Scherrer, Williamson-Hall, Size-Strain Plot and Halder-Wagner method have been applied to study the crystal structure characteristics. The lattice parameters associated with the monoclinic crystal lattice of CuO NPs were estimated to be a = 4.69 Å, b = 3.41 Å, c = 5.14 Å and β = 99.87(degree), unit cell volume V = 81.35Å3 and cell density dx = 6.49 g/cm3. The photocatalytic dye degradation proficiency at 20 mg/l CuO concentration and 120 min sunlight exposure results the order of percentage dye degradation Malachite Green (88.4%) > Crystal Violet (70.8%) > Eosin Yellow (70.2%) > Methylene Blue (54.08%) dyes. The antimicrobial activity assessment was done against the broad-spectrum pathogenic microbes unveiled the exceptional microbial controlling capability of CuO NPs. Furthermore, the antioxidant activity test demonstrated the potential free radical scavenging activity of CuO NPs with an IC50 value of 47.733 µg/ml. Highlights Synthesis of pure and spherical shaped nanocrystalline CuO was done by using low cost and facile chemical coprecipitation method. XRD, FTIR, FESEM, EDX, UV-Vis, and Raman spectroscopic techniques were used for characterization purpose. The structural and crystallographic parameters of monoclinic crystal structure of CuO NPs were evaluated successfully. The photocatalytic performance of CuO NPs follow the percentage dye degradation order as MG (88.4%) > CV (70.8%) > EY (70.20%) > MB (54.08%) after 120 minutes of sunlight exposure. CuO NPs exhibit promising antifungal activity against COVID-19 associated Pulmonary Aspergillosis (CAPA) causing pathogenic fung. CuO NPs show potential DPPH free radical scavenging activity with an IC50 value of 47.733 µg/ml.

Anti-Sporothrix activity of novel copper-itraconazole complexes.

A series of new metal complexes, [Cu(ITZ)2Cl2]·5H2O (1), [Cu(NO3)2(ITZ)2] ·3H2O·C4H10O and [Cu(ITZ)2)(PPh3)2]NO3·5H2O (3) were synthesized by a reaction of itraconazole (ITZ) with the respective copper salts under reflux. The metal complexes were characterized by elemental analyses, molar conductivity, 1H and 13C{1H} nuclear magnetic resonance, UV-Vis, infrared and EPR spectroscopies. The antifungal activity of these metal complexes was evaluated against the main sporotrichosis agents: Sporothrix brasiliensis, Sporothrix schenkii, and Sporothrix globosa. All three new compounds inhibited the growth of S. brasiliensis and S. schenckii at lower concentrations than the free azole, with complex 2 able to kill all species at 4 µM and induce more pronounced alterations in fungal cells. Complexes 2 and 3 exhibited higher selectivity and no mutagenic effect at the concentration that inhibited fungal growth and affected fungal cells. The strategy of coordinating itraconazole (ITZ) to copper was successful, since the corresponding metal complexes were more effective than the parent drug. Particularly, the promising antifungal activity of the Cu-ITZ complexes makes them potential candidates for the development of an alternative drug to treat mycoses.

Antifungal and antibiofilm effect of duloxetine hydrochloride against Cryptococcus neoformans and Cryptococcus gattii.

Cryptococcosis is an invasive mycosis caused mainly by Cryptococcus gattii and C. neoformans and is treated with amphotericin B (AMB), fluconazole and 5-fluorocytosine. However, antifungal resistance, limited and toxic antifungal arsenal stimulate the search for therapeutic strategies such as drug repurposing. Among the repurposed drugs studied, the selective serotonin reuptake inhibitors (SSRIs) have shown activity against Cryptococcus spp. However, little is known about the antifungal effect of duloxetine hydrochloride (DH), a selective serotonin and norepinephrine reuptake inhibitor (SSNRI), against C. neoformans and C. gattii. In this study, DH inhibited the growth of several C. neoformans and C. gattii strains at concentrations ranging from 15.62 to 62.50µg/mL. In addition, DH exhibited fungicidal activity ranging from 15.62 to 250µg/mL. In biofilm, DH treatment reduced Cryptococcus spp. biomass at a level comparable to AMB, with a significant reduction (85%) for C. neoformans biofilms. The metabolic activity of C. neoformans and C. gattii biofilms decreased significantly (99%) after treatment with DH. Scanning electron micrographs confirmed the anti-biofilm activity of DH, as isolated cells could be observed after treatment. In conclusion, DH showed promising antifungal activity against planktonic cells and biofilms of C. neoformans and C. gattii, opening perspectives for further studies with DH in vivo.

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.

Comparative in vitro analysis of the antifungal activity of different calcium silicate-based endodontic sealers

Aim: This study aimed to perform an in vitro comparative analysis of the antifungal activity of different calcium silicate-based endodontic sealers against three fungal species. Methods: The antifungal properties of three calcium silicate-based sealers were tested: Bio-C Sealer, Cambiar a Sealer Plus BC, and MTA-Fillapex. Two commonly used sealers were used as controls: AH Plus and Endomethasone. An agar diffusion test was performed to analyze the antifungal activity of the sealers against Candida albicans, Candida glabrata, Candida tropicalis, and a mixed microbial culture medium. The results were analyzed using ANOVA (p <0.05). Results: Endomethasone exhibited the highest inhibition against all strains examined, maintaining a consistent level of inhibition throughout 7 days. MTA-Fillapex demonstrated the best performance among the calcium silicate-based sealers for the three fungal species (p < 0.05), maintaining stable values over the 7 days, surpassing that of Endomethasone. Nevertheless, MTA-Fillapex only exhibited antimicrobial effect against the mixed culture for the first 24 hours, and no antimicrobial activity was observed at 48 hours, being surpassed by all tested sealers (p < 0.05). Conclusion: Of all silicate-based sealers tested, only MTA-Fillapex exhibited promising antifungal activity. Nevertheless, care must be taken when extrapolating these results, as MTA-Fillapex exhibited poor antimicrobial activity when tested in mixed microbial cultures.

Nickel oxide nanoparticles as sustainable catalysts for efficient synthesis and anti-microbial evaluation of 2-amino-4H-pyran derivatives

In the current paper, nickel oxide nanoparticles (NiO NPs) was successfully applied as a sustainable effective and recoverable catalyst for the preparation of 2-amino-4H pyran derivatives 2-11 via one-pot, three-component reaction of 4-formylphenyl-4-methyl benzenesulfonate (1) with malononitrile and active methylene compounds in green solvent water and ethanol in ratio (3:1) in excellent yield (95-98%) and shorter reaction time (5-8 min). The structures of the pyran derivatives were elucidated by elemental and spectral analyses such as IR, 1H NMR, 13C NMR and DEPT 135 spectra. Moreover, the characterization of the catalyst after and before the reaction were studied using X-ray diffraction (X-RD), scanning electron microscope (SEM), EDX techniques and IR-spectra. It has been indicated that catalyst has the same efficiency. The application of this protocol has many advantages such as eco-friendly, inexpensive, simple protocol and easy recovery of the catalyst. Overall products are designed, synthesized and studied for their anti-microbial evaluation. It has been found that is compounds 2, 3, 7 and 10 are the most active against antibacterial compression with the stander drug Ampicillin. On the other hand, Compounds 2, 3, 8, and 11 displayed the most promising antifungal activities with Amphotericin B.
 KEY WORDS: Nickel oxide nanoparticles, Pyran derivatives, X-Ray diffraction (X-RD), Antimicrobial evaluation, One-pot, Three-component reaction
 Bull. Chem. Soc. Ethiop. 2024, 38(3), 657-670. 
 DOI: https://dx.doi.org/10.4314/bcse.v38i3.9

Design, Synthesis, Antifungal Activity, and 3D-QASR of Novel Oxime Ether-Containing Coumarin Derivatives as Potential Fungicides.

Structural modification of natural products is an effective approach for improving antifungal activity and has, therefore, been used extensively in the development of new agrochemical products. In this work, a series of novel coumarin derivatives containing oxime ether structures were designed, synthesized, and evaluated for antifungal activity. Some of the designed compounds exhibited promising antifungal activities against tested fungi, and compounds 4a, 4c, 5a, and 6b had EC50 values equivalent to those of commercial fungicides. Compound 6b was the most promising candidate fungicide against Rhizoctonia solani (EC50 = 0.46 μg/mL). In vivo antifungal bioassays suggested that compounds 5a and 6b could serve as novel agricultural antifungals. Furthermore, microscopy demonstrated that compound 6b induced the sprawling growth of hyphae, distorted the outline of cell walls, and reduced mitochondrial numbers. Additionally, the effects of the substituent steric, electrostatic, hydrophobic, and hydrogen-bond fields were elucidated using an accurate and reliable three-dimensional quantitative structure-activity relationship (3D-QSAR) model. The results presented here will guide the discovery of potential novel fungicides for plant disease control in agriculture.

Phytochemical Characterization, Antimicrobial Activity, Pharmacokinetic, in silico Molecular Docking and Interaction Analysis of Ajwa (Phoenix dactylifera L.) Palm Date Seeds

Background: There is growing evidence that antibiotic resistance is increasing. As a result, the efficacy of these antibiotics is gradually declining. This poses a serious health risk in terms of treatment strategies. Therefore, the scientific community is continuously putting all efforts into looking for novel and green therapeutics to overcome the problem of antibiotic resistance. Objectives: The aim of this study is to investigate the chemical composition of the methanolic extracts obtained from Phoenix dactylifera seeds, known agricultural waste, to identify new bioactive compounds and to examine the antibacterial and antifungal potentials. Materials and Methods: Phytochemical profiling was performed by the gas chromatography-mass spectrometry (GC-MS) technique. For the antibacterial activity of the methanolic extract, 12 microorganisms were selected, including eight bacteria ( Escherichia coli ATCC 35218, Pseudomonas aeruginosa ATCC 27853, Enterobacter cloacae, Enterococcus faecium, Staphylococcus hominis, Staphylococcus aureus, Staphylococcus epidermidis, and Klebsiella pneumoniae ATCC 27736) and four Candida species (C. albicans ATCC 10231, C. tropicalis ATCC 1362, C. utilis ATCC 9255, and C. guilliermondii ATCC 6260). The antimicrobial activity of the plant extract was supported by in silico molecular docking analysis. Results: The obtained results from the GC-MS technique revealed the presence of 51 compounds, of which 6-octadecenoic acid (Z) was identified as the major component. The tested extract exhibited the highest zone of inhibition against S. aureus (growth inhibition zone 14.66 ± 0.57 mm). In addition, minimal inhibitory concentration (MIC) and minimal bactericidal concentration values obtained against S. aureus were 1.4 and 5.6 mg/mL, respectively. Regarding the antifungal assay, C. albicans was the most sensitive one to the extract among all the tested Candida strains (14.33 mm) (MIC: 1.4 mg/mL, minimal fungicidal concentration (MFC): 11.2 mg/mL). The binding free energies and root mean square deviation values obtained from the interaction of phytochemicals with two different target receptors (1JIJ and 2QZW for TyrRS from S. aureus and aspartic proteinase from C. albicans) were also determined. Ergost-5-en-3-ol, (3beta) established hydrogen, electrostatic, alkyl, and pi-alkyl interactions with five different amino acid residues (Asp40, Asp80, Pro53, His50, and Phe54) located at the TyrRS receptor of S. aureus. On the other hand, hexadecanoic acid and methyl ester established hydrogen, electrostatic, pi-sigma, and alkyl interactions with five different amino acid residues (Thr222, Asp86, Asp218, Tyr84, and Ile123) located at the aspartic proteinase receptor of C. albicans. These interactions contributed to the stability of the complex and, hence, to the biological activity of the P. dactylifera compounds. Conclusion: Our results highlighted that methanolic extract from date seeds can be a natural source of chemical compounds with promising antibacterial and antifungal activities, as demonstrated using both in vitro and in silico approaches.

Antioxidant, Immunomodulatory and Fungicidal Potential of Different Extracts of Raphanus Raphanistrum L. Var. Caudatus

Background: Reactive oxygen species (ROS) have been implicated in the pathogenesis of various diseases, emphasizing the importance of antioxidants in maintaining cellular homeostasis. Raphanus raphanistrum, commonly known as wild radish, has been traditionally used for its medicinal properties, including antioxidant, immunomodulatory, and antifungal effects. The plant is rich in bioactive compounds such as flavonoids, isothiocyanates, and vitamins, which contribute to its therapeutic potential. Objective: This study aimed to evaluate the antioxidant, immunomodulatory, and antifungal activities of Raphanus raphanistrum extracts and to compare these activities with standard controls. Methods: Fresh Raphanus raphanistrum plants were collected, and extracts were prepared using methanol, chloroform, and water. The antioxidant activity was assessed using the DPPH radical scavenging assay. Immunomodulatory activity was evaluated through the luminol-enhanced chemiluminescence assay in whole blood and polymorphonuclear leukocytes (PMNS), measuring the oxidative burst. The antifungal activity was determined using the agar disk diffusion method against six pathogenic fungi. The statistical analysis was performed using SPSS version 25, with results presented as mean ± standard deviation for antioxidant and antifungal assays, and mean ± standard error for immunomodulatory activity. Results: The methanol extract exhibited significant antioxidant activity with DPPH scavenging percentages ranging from 56.55% at 150 µg/ml to 87.08% at 850 µg/ml. Immunomodulatory activity showed IC50 values of 37.8 µg/ml in whole blood and 18.9 µg/ml in PMNS for the methanol extract. The antifungal activity against Candida albicans showed zones of inhibition increasing from 15 mm at 150 µg/ml to 22 mm at 850 µg/ml. These activities were compared to standard controls, including ascorbic acid for antioxidant, ibuprofen for immunomodulatory, and miconazole for antifungal assays, demonstrating the extracts' competitive potential. Conclusion: Raphanus raphanistrum extracts showed promising antioxidant, immunomodulatory, and antifungal activities, indicating their potential as natural alternatives for the prevention and treatment of related diseases. Further in vivo studies and isolation of active compounds are recommended to fully understand the mechanisms and therapeutic applications.

Synthesis, characterization, in silico and in vitro studies of novel glycoconjugates as potential antibacterial, antifungal, and antileishmanial agents

Abstract In the present work, several new glycoconjugates (8a–e) were generated from glycopyranosyl-α-trichloroacetimidates (sugar-OTCA) as glycosyl donors and dimethyl-l-tartrate as an aglycone acceptor in good to excellent yields. In the synthetic protocol, various monosaccharides were transformed into pentaacetylated derivatives and then into glycopyranosyl-α-trichloroacetimidates. Afterward, the sugar-OTCA was reacted with dimethyl-l-tartrate using Schmidt’s trichloroacetimidate protocol to give the desired products. The newly synthesized glycoconjugates were characterized by FT-IR, 1H, and 13C-NMR spectroscopic analytical methods. All the target compounds (8a–e) were tested in vitro against various strains of bacteria and fungi at different concentrations. The results revealed that the target compounds had encouraging antibacterial and antifungal potential. The antileishmanial activity of the target compounds against Leishmania tropica promastigotes was also investigated. The in vitro results were further supported by the in silico docking study that indicated minimum values of the docking scores and binding energies for the resulting complexes obtained by the favorable interactions between the target compounds (8a–e) and the selected strains of bacteria and fungi. The docking results proposed promising antibacterial and antifungal activities of the target compounds (8a–e) against the selected bacterial and fungal species.

Synthesis and characterization of new palladium (II) and silver (I) thiosemicarbazone derived by acenaphthenequinone complexes and their antimicrobial activity

The ability of substituted acenaphthenequinone-thiosemicarbazones to do complexation with Pd(II) and Ag(I) salts was investigated. The obtained Pd(II) 5a-f and Ag(I) 7a-f complexes showed that ligation was occurred during the reaction of two equivalents of the ligands with one equivalent of the metal salts. In case of Pd complexes 5a-f, two moles of HCl were eliminated during complexation process. Whereas direct ligation was occurred during complexation of one mole of AgNO3 and two moles of ligands to form the corresponding cationic-anionic salts 7a-f. IR, NMR, and UV–vis spectra were used to deduce the structure of the formed metal complexes. X-ray structure analysis proved the syn-form of bis(bidentate) structure of Pd complex 5e, as Pd showed a square planar coordination with two sulfur and two nitrogen atoms. The cationic-anionic nature of silver complexes was revealed by molar conductance. UV–visible spectra were also investigated by means of Time-Dependent Density-Functional Theory (TD-DFT) computations. The obtained metal complexes were also investigated asantibacterial and antifungal agents. Compounds 5f, 5e, 7d, and 7f were found to be the most active and effective against the four bacterial strains, with compound 7f having the most potent action. Compound 7f (R = 3-OMe-Ph) showed MIC values of 0.066, 0.018, 0.018, and 0.033 µg/mL against B. subtilis, S. aureus, E. coli, and K. pneumoniae, respectively. For compound 7d (R = Benzyl), the MIC values are found as 0.028, 0.057, 0.028, and 0.028 µg/mL against the same previous bacterial strains. Compounds 5d, 5e, 7c, and 7f demonstrated promising antifungal activity against C. albicans with MIC values of 0.029, 0.023, 0.018, and 0.027 µg/ml, respectively, when compared to the reference fluconazole, which had a MIC value of 0.020 µg/ml. Compound 7f revealed inhibitory activity of E. coli DNA gyrase (IC50 = 210 ± 15 nM, respectively) being 1.2-folds less potent than the reference novobiocin (IC50 = 170 ± 20 nM).

Novel azole-sulfonamide conjugates as potential antimicrobial candidates: synthesis and biological assessment.

Background: Azole and sulfonamide molecular frameworks are endowed with potent antimicrobial activity. Materials & methods: A series of azole-sulfonamide conjugates were synthesized using click reaction of N-propargylated imidazole with azide of sulfonamide and its antimicrobial efficacy was evaluated. Results: The compounds 7c, 7i and 7r displayed promising antibacterial activities, better than the standards sulfonamide and norfloxacin. Allmolecules exhibited promising antifungal activity, more potent than fluconazole. Docking studies of the active conjugates signified the importance of hydrophobic interactions in hosting the molecules in theactive site of dihydrofolate reductase. Conclusion: Azole-sulfonamide conjugates are more active than single sulfonamide moieties and 7c, 7i and 7r may prove valuable leads for further optimization as novel antimicrobial agents.

Assessment of solar light sensitive Chitosan integrated CeO2-CuO ternary composites for the efficient degradation of Malachite Green, Acid Blue 113 dyes and microbial studies

Ternary chitosan integrated CeO2-CuO composites were prepared via a facile co-precipitation technique and thoroughly characterized using FTIR spectroscopy, X-ray diffraction, UV-diffuse reflectance spectroscopy, Thermo gravimetric analysis, Scanning emission microscopy, Transmission electron microscopy and X-ray Photoelectron spectroscopy. The composite with 10 wt% CeO2-CuO on chitosan exhibited the highest efficiency of 92 % and 91 % in degrading malachite green (MG) and acid blue 113 (AB 113) respectively. This composite demonstrated efficient generation of electron-hole pairs, minimized recombination rates and facilitated rapid dye degradation under solar light illumination. Additionally, the composites displayed effective antibacterial activity against Serratia marcescens and Bacillus subtilis at a concentration of 100 µl, and exhibited promising anti-fungal activities against Candida albicans and Aspergillus niger. These findings suggest the potential of these composites for efficient dye degradation and demonstrate their promising antimicrobial properties, offering possibilities for diverse environmental and biomedical applications.

Chemical composition of five essential oils and their antioxidant and in vitro and in vivo antifungal activities against Alternaria alternata in tomato crop

This study aimed to determine the chemical composition of essential oils from A. gratíssima, O. basilicum, S. microphylla, T. riparia, and T. vulgaris and their antioxidant and antifungal activities against Alternaria alternata strains. Gas chromatography-mass spectrometry revealed that the major components of the essential oils were terpenes. The essential oils of S. microphylla and T. riparia showed higher antioxidant activities than the others. The essential oils of S. microphylla and T. riparia inhibited the growth of the fungus at 3.10 and 6.05 µL/mL, respectively. The essential oil of T. riparia inhibited 93.9% of the growth of the fungus and showed the highest in vivo efficiency in severity reduction (76.2%). We conclude that the essential oil of T. riparia shows promising antifungal activity and is an environmentally safe alternative for controlling fungal diseases in vegetables.

Formulation and evaluation of Chinese eucalyptus oil gel by using different gelling agents as an antimicrobial agent

BackgroundThe aim of the present study was to formulate and evaluate the herbal gels containing Chinese Eucalyptus Oil or Eucalyptus globulus Labill. (E. globulus) using different polymers (Methylcellulose, HPMC, Carbopol-940) and checked their antimicrobial effects against different microorganisms. the oil from Eucalyptus globulus has a good medicinal value in the Chinese medicine system. MethodsA topical gels formulation were designed by using mentioned oil with polymers, as well as gelling agent with different excipients. Microbial species, such as Staphylococcus aureus (S. aureus), Bacillus subtilis (B. subtilis), Escherichia coli (E. coli), Pseudomonas aeruginosa (P. aeruginosa), Aspergillus tubingensis (A. tubingensis) have been selected for the study. ResultsThe gel's physical properties complied with the necessary standards. These four gel compositions efficiently stop some strains' development. Studies show that the gel was also particularly effective against gram-negative and fungal bacteria. The Zones of inhibition (ZOI) were found between 1.2 and 10.2 µm. The formulation F4 have good antifungal potential. ConclusionThe herbal gel was found to have highly promising anti-fungal and anti-fungal activity against many skin-related infections in a concentration-dependant manner but further research must be needed.

Quinolone Tethered 1,2,3-triazole Conjugates: Design, Synthesis, and Computational Docking Studies on New Heterocycles as Potent Antimicrobial Targets

Abstract: The synthesis and biological properties of molecules simultaneously comprising various heterocycles, such as fused 2-quinolones and 1,2,3-triazoles, have been evaluated as a part of our ongoing research in medicinal and organic chemistry. We were successful in developing a synthetic procedure for 1,2,3-triazole substituted quinolone derivatives. Infrared, proton, and carbon nuclear magnetic resonance, mass spectroscopy and elemental analysis were used to characterise the structures of the recently synthesised triazole derivatives. From screening results, all the compounds demonstrated increased antibacterial action against both Gram-positive and Gram-negative bacteria. Moreover, 1,2,3-triazoles linked to tert-butyl benzyl (3a), trifluoromethyl benzyl (3b), 3-chlorobenzyl (3c), 4- hydroxy-3-nitrobenzyl (6b), 4-hydroxy-4-trifluoromethylbenzyl (6d), and 4-hydroxy-2,4- difluorobenzyl (6e) compounds showed promising antibacterial and antifungal activities with MICs values of 1.07-4.33 μg/mL. The prepared ligand 4-hydroxy-2,4-difluoro benzyl-1,2,3-triazole (6e) exhibited the highest docking score of -6.34 kcal/mol and showed interacting amino acid residues ArgB:1122, MetB:1121, AspB:1083, TryB:1087, AlaB:1118, AlaB:1120, GluB:1088, GlyB:1117, SerB:1084, and AlaB:1119 within the active site of 2XCT. Final scaffolds were further evaluated for their ADMET and physicochemical properties by using ADMETlab2.0 and SwissADME web servers as good oral bioavailability drugs.

Novel quinoxalinone-1,2,3-triazole derivatives as potential antifungal agents for plant anthrax disease: Design, synthesis, antifungal activity and SAR study

A series of quinoxalinone-1,2,3-triazole derivatives have been synthesized and tested for antifungal activity against phytopathogenic fungus through mycelial growth inhibition in vitro, spore germination inhibition in vitro and control effect in vivo. The results showed that the pharmacophore quinoxalinone and 1,2,3-triazole displayed promising antifungal activity. The EC50 value against C. gloeosporioides of 6a-1 was 1.17 μg/mL and the compound 6c-1 showed the good bioactivity against C. fragariae Brooks and P. oryzae Cav., displaying EC50 values of 5.56, 4.62 μg/mL, respectively. The inhibitory of spore germination by 6a-1 was performed with EC50 value of 1.91 μg/mL. In addition, the in vivo bioassay indicated that 6a-1 possessed effective control against Pepper Anthrax Disease in protective treatment. For given activity data of target compounds, structure-activity relationship (SAR) study was operated, hoping for optimizing the target structure to find lead compound with higher activity.

The Polyketides with Antimicrobial Activities from a Mangrove Endophytic Fungus Trichoderma lentiforme ML-P8-2.

Five new polyketides, including two chromones (1-2), two phenyl derivatives (4-5), and a tandyukusin derivative (6), along with five known polyketides (3 and 7-10) were isolated from mangrove endophytic fungus Trichoderma lentiforme ML-P8-2. The planar structures of compounds were elucidated via detailed 1D, 2D NMR, and HR-ESI-MS analysis. ECD spectra, optical rotation values calculation, and alkali hydrolysis were applied in the determination of the absolute configuration of the new compounds. In bioassays, 6 and 9 exhibited promising antifungal activities against Penicillium italicum, with an MIC value of 6.25 μM for both compounds. Moreover, 3 displayed moderate AChE inhibitory activity with an IC50 value of 20.6 ± 0.3 μM.

Natural terpene-based derivatives to control postharvest sclerotinia rot and the involved potential mechanism

In an effort to develop novel postharvest preservatives of satisfactory environmental compatibility from natural monoterpene, a series of terpene-based derivatives containing oxime ester were designed and prepared. In this research, the inhibitory effect of target compounds against S. sclerotiorum were evaluated though in vitro and in vivo tests. It was investigated that most compounds exhibited promising antifungal activity, especially compound 4k with EC50 value of 3.02 μg/mL, which was significantly superior to commercial fungicide trifloxystrobin. Notably, compound 4k improved the physicochemical quality of carrot including weight loss, contents of titratable acidity, ascorbic acid, carotenoid, malondialdehyde, and enzymes activities, ensuring post-harvest preservation. Simultaneously, the mycelial morphology, ultrastructure, cell wall permeability, and defense/respiration-related enzymes of S. sclerotiorum were destructed. The preliminary toxicity evaluation of target compounds indicated that the prepared target compounds possessed safety and low toxicity. Additionally, the essential chemical features for activity and interaction mode between molecule and cytochrome bc1 complex were inquired by computer-aid technology. The study provided meaningful insight into formulation of natural terpene-based fresh-keeping agent to resist postharvest decay infected by S. sclerotiorum.

The antifungal activity and mechanism of Perillaldehyde and its stabilized encapsulation technology for fruit preservation

Perillaldehyde (PAE), an essential oil extracted from perilla (Perilla frutescens (L.) Britt.), exhibits excellent antioxidant and antimicrobial activity. In this study, we found that the antifungal mechanism of PAE was attributed to the stimulation of ROS levels, destruction of mitochondrial function, and induction of spore apoptosis. Transcriptomic analysis showed that the gene expression pattern of Botrytis cinerea significantly changed after PAE treatment, and the differentially expressed genes (DEGs) were mainly involved in the MAPK signaling pathway and cell wall integrity pathway. For the better utilization of PAE for fruit preservation, the inclusion complex (IC) of PAE and hydroxypropyl-β-cyclodextrin was successfully synthesized by ultrasonic-assisted method, as proved by UV–vis spectroscopy, fourier transform infrared spectroscopy, thermal properties analysis, scanning electron microscopy, and 1H NMR. It was demonstrated that water solubility and thermal stability of PAE/HPβCD-IC were significantly improved compared to pure PAE. Furthermore, both in vitro and in vivo antifungal assessment showed that PAE/HPβCD-IC was effective for inhibiting B. cinerea. Overall, our results indicated that PAE/HPβCD-IC had promising antifungal activity, water solubility and thermal stability, which provided a theoretical basis for the utilization of PAE/HPβCD-IC for fruit preservation.