Isolation of triazole-resistant Aspergillus fumigatus harbouring cyp51A mutations from five patients with invasive pulmonary aspergillosis in Yunnan, China.

Invasive aspergillosis (IA) is the most severe type of Aspergillus infection. Yunnan has developed agriculture, and the proportion of triazole-resistant A. fumigatus induced by triazole fungicides is much higher than that in other regions of China. Inhalation of triazole-resistant A. fumigatus is one of the main factors inducing IA. We gathered five strains of A. fumigatus from the sputum or bronchoalveolar lavage fluid (BALF) of patients with IA in Yunnan. Subsequent testing showed that all of these strains were resistant to triazoles and harboured mutations in the tandem repeat sequence of the cyp51A promoter region, suggesting that they may be triazole-resistant A. fumigatus present in the environment.

Highly Dense N-N-Bridged Dinitramino Bistriazole-Based 3D Metal-Organic Frameworks with Balanced Outstanding Energetic Performance.

Due to the inherent conflict between energy and safety, the construction of energetic materials or energetic metal-organic frameworks (E-MOFs) with balanced thermal stability, sensitivity, and high detonation performance is challenging for chemists worldwide. In this regard, in recent times self-assembly of energetic ligands (high nitrogen- and oxygen-containing small molecules) with alkali metals were probed as a promising strategy to build high-energy materials with excellent density, insensitivity, stability, and detonation performance. Herein, based on the nitrogen-rich N,N'-([4,4'-bi(1,2,4-triazole)]-3,3'-dial)dinitramide (H2BDNBT) energetic ligand, two new environmentally benign E-MOFs including potassium [K2BDNBT]n (K-MOF) and sodium [Na2BDNBT]n (Na-MOF) have been introduced and characterized by NMR, IR, TGA-DSC, ICP-MS, PXRD, elemental analyses, and SCXRD. Interestingly, Na-MOF and K-MOF demonstrate solvent-free 3D dense frameworks having crystal densities of 2.16 and 2.14 g cm-3, respectively. Both the E-MOFs show high detonation velocity (VOD) of 8557-9724 m/s, detonation pressure (DP) of 30.41-36.97 GPa, positive heat of formation of 122.52-242.25 kJ mol-1, and insensitivity to mechanical stimuli such as impact and friction (IS = 30-40 J, FS > 360 N). Among them, Na-MOF has a detonation velocity (9724 m/s) superior to that of conventional explosives. Additionally, both the E-MOFs are highly heat-resistant, having higher decomposition (319 °C for K-MOF and 293 °C for Na-MOF) than the traditional explosives RDX (210 °C), HMX (279 °C), and CL-20 (221 °C). This stability is ascribed to the extensive structure and strong covalent interactions between BDNBT2- and K(I)/Na(I) ions. To the best of our knowledge, for the first time, we report dinitramino-based E-MOFs as highly stable secondary explosives, and Na-MOF may serve as a promising next-generation high-energy-density material for the replacement of presently used secondary thermally stable energetic materials such as RDX, HNS, HMX, and CL-20.

Synthesis, physicochemical characterization, and investigation of anti-inflammatory activity of water-soluble PEGylated 1,2,4-Triazoles.

A series of water-soluble PEGylated 1,2,4-triazoles 5-8 were successfully synthesized from methyl 5-(chloromethyl)-1-aryl-1H-1,2,4-triazole-3-carboxylates 1. All of the water-soluble PEGylated 1,2,4-triazoles were characterized by FT-IR and 1H NMR spectroscopy. The solubility, in vitro plasma stability, and anti-inflammatory activity were also determined and compared to original methyl 5-(halomethyl)-1-aryl-1H-1,2,4-triazole-3-carboxylates. For SAR study, all PEGylated 1,2,4-triazoles 5-8 performed potential anti-inflammatory activity on LPS-induced RAW 264.7 cells (IC50 = 3.42-7.81 µM). Moreover, the western blot result showed PEGylated 1,2,4-triazole 7d performed 5.43 and 2.37 folds inhibitory activity over iNOS and COX-2 expressions. On the other hand, the cell viability study revealed PEGylated 1,2,4-triazoles 7 and 8 with PEG molecular weight more than 600 presented better cell safety (cell viability > 95 %). Through the solubility and in vitro plasma stability studies, PEGylated 1,2,4-triazoles 7a-d exhibited higher hydrophilicity and prolonged 2.01 folds of half-life in compound 7d. Furthermore, the in vivo anti-inflammatory and gastric safety results indicated PEGylated 1,2,4-triazole 7d more effectively decreased the inflammatory response in edema and COX-2 expression and exhibited higher gastric safety than Indomethacin. Following the in vitro and in vivo study results, PEGylated 1,2,4-triazole 7d possessed favorable solubility, plasma stability features, safety, and significant anti-inflammatory activity to become the potential water-soluble anti-inflammatory candidate.

New phenylthiosemicarbazide-phenoxy-1,2,3-triazole-N-phenylacetamides as dual inhibitors against α-glucosidase and PTP-1B for the treatment of type 2 diabetes.

This study describes the design, synthesis, and evaluation of a novel series of phenylthiosemicarbazide-phenoxy-1,2,3-triazole-N-phenylacetamide derivatives (7a-l) as dual inhibitors of α-glucosidase and protein tyrosine phosphatase 1-B (PTB-1B). The latter enzymes are two important targets in the treatment of type 2 diabetes. The in vitro obtained data demonstrated that all title compounds 7a-l were more potent than the standard inhibitor acarbose against α-glucosidase while only four derivatives (7a, 7g, 7h, and 7h) were more potent than the standard inhibitor suramin against PTP-1B. Furthermore, these data showed that the most potent α-glucosidase inhibitor was compound 7i, with sixfold higher inhibitory activity than acarbose, and the most potent PTP-1B inhibitor was compound 7a with 3.5-fold higher inhibitory activity than suramin. Kinetic studies of compounds 7i and 7a revealed that they inhibited their target enzymes in a competitive mode. The docking study demonstrated that compounds 7i and 7a well occupied the active site pockets of α-glucosidase and PTP-1B, respectively. In silico pharmacokinetic and toxicity assays of the most potent compounds were performed, and the obtained results were compared with those of the standard inhibitors.

Efficient, rapid, and high-yield synthesis of aryl Schiff base derivatives and their in vitro and in silico inhibition studies of hCA I, hCA II, AChE, and BuChE.

This study reports a rapid and efficient synthesis of four novel aryl Schiff base derivatives. Biological activity and molecular modeling studies were conducted to evaluate the inhibitory effects of these compounds on human carbonic anhydrases (hCA) and cholinesterases. The results indicate that the triazole-ring-containing compounds have strong inhibitory effects on hCA I, hCA II, acetylcholinesterase (AChE), and butyrylcholinesterase (BuChE) targets. Besides comparing the Schiff bases synthesized in our study to reference molecules, we conducted in silico investigations to examine how these compounds interact with their targets. Our studies revealed that these compounds can occupy binding sites and establish interactions with crucial residues, thus inhibiting the functions of the targets. These findings have significant implications as they can be utilized to develop more potent compounds for treating the diseases that these target proteins play crucial roles in or to obtain drug precursors with enhanced efficacy.

Evaluating cardiac disorders associated with triazole antifungal agents based on the US Food and Drug Administration Adverse Event reporting system database.

Introduction: Triazole antifungal agents are widely used to treat and prevent systemic mycoses. With wide clinical use, the number of reported adverse events has gradually increased. The aim of this study was to analyze the cardiac disorders associated with TAAs (fluconazole, voriconazole, itraconazole, posaconazole and isavuconazole) based on data from the US Food and Drug Administration Adverse Event Reporting System FDA Adverse Event Reporting System. Methods: Data were extracted from the FAERS database between the first quarter of 2004 and third quarter of 2022. The clinical characteristics in TAA-associated cardiac AE reports were analyzed. Disproportionality analysis was performed to evaluate the potential association between AEs and TAAs using the reporting odds ratio (ROR) and proportional reporting ratio (PRR). Results: Among 10,178,522 AE reports, 1719 reports were TAA-associated cardiac AEs as primary suspect drug. Most reports were related to fluconazole (38.34%), voriconazole (28.56%) and itraconazole (26.76%). Itraconazole (N = 195, 42.39%) and isavuconazole (N = 2, 14.29%) had fewer serious outcome events than three other drugs including fluconazole, voriconazole, and posaconazole. 13, 11, 26, 5 and 1 signals were detected for fluconazole, voriconazole, itraconazole, posaconazole and isavuconazole, respectively. The number of new signals unrecorded in the drug label was 9, 2, 13, 2 and 0 for fluconazole, voriconazole, itraconazole, posaconazole and isavuconazole, respectively. Conclusion: Isavuconazole might be the safest of the five TAAs for cardiac AEs. TAA-associated cardiac disorders may result in serious adverse outcomes. Therefore, in addition to AEs on the drug label, we should pay attention to new AEs unrecorded on the drug label during the clinical use of TAAs.

Novel 1,2,4-triazoles as selective carbonic anhydrase inhibitors showing ancillary anticathepsin B activity.

Background: Exploration of the multi-target approach considering both human carbonic anhydrase (hCA) IX and XII and cathepsin B is a promising strategy to target cancer. Methodology & Results: 22 novel 1,2,4-triazole derivatives were synthesized and evaluated for their inhibition efficacy against hCA I, II, IX, XII isoforms and cathepsin B. The compounds demonstrated effective inhibition against hCA IX and/or XII isoforms with considerable selectivity over off-target hCA I/II. All compounds presented significant anticathepsin B activities at a low concentration of 10-7 M and in vitro results were also supported by the molecular modeling studies. Conclusion: Insights of present study can be utilized in the rational design of effective and selective hCA IX and XII inhibitors capable of inhibiting cathepsin B.

1,2,3-Triazole Hybrids Containing Isatins and Phenolic Moieties: Regioselective Synthesis and Molecular Docking Studies.

The synthesis of hybrid molecules is one of the current strategies of drug discovery for the development of new lead compounds. The 1,2,3-triazole moiety represents an important building block in Medicinal Chemistry, extensively present in recent years. In this paper, we presented the design and the synthesis of new 1,2,3-triazole hybrids, containing both an isatine and a phenolic core. Firstly, the non-commercial azide and the alkyne synthons were prepared by different isatines and phenolic acids, respectively. Then, the highly regioselective synthesis of 1,4-disubstituted triazoles was obtained in excellent yields by a click chemistry approach, catalyzed by Cu(I). Finally, a molecular docking study was performed on the hybrid library, finding four different therapeutic targets. Among them, the most promising results were obtained on 5-lipoxygenase, an enzyme involved in the inflammatory processes.

Unveiling potent Schiff base derivatives with selective xanthine oxidase inhibition: In silico and in vitro approach.

This research describes the synthesis by an environmentally-friendly method, microwave irradiation, development and analysis of three novel and one previously identified Schiff base derivative as a potential inhibitor of bovine xanthine oxidase (BXO), a key enzyme implicated in the progression of gout. Meticulous experimentation revealed that these compounds (10, 9, 4, and 7) have noteworthy inhibitory effects on BXO, with IC50 values ranging from 149.56 µM to 263.60 µM, indicating their good efficacy compared to that of the standard control. The validation of these results was further enhanced through comprehensive in silico studies, which revealed the pivotal interactions between the inhibitors and the catalytic sites of BXO, with a particular emphasis on the imine group (-C = N-) functionalities. Intriguingly, the compounds exhibiting the highest inhibition rates also showcase advantageous ADMET profiles, alongside encouraging initial assessments via PASS, hinting at their broad-spectrum potential. The implications of these findings are profound, suggesting that these Schiff base derivatives not only offer a new vantage point for the inhibition of BXO but also hold considerable promise as innovative therapeutic agents in the management and treatment of gout, marking a significant leap forward in the quest for more effective gout interventions.

Rational Design and Synthesis of Isatin-Chalcone Hybrids Integrated with 1H-1,2,3-Triazole: Anti-proliferative Profiling and Molecular Docking Insights.

In this study, a series of isatin-chalcone linked triazoles were synthesized using Cu-promoted Azide-Alkyne Cycloaddition (CuAAC) reaction and evaluated for their cytotoxicity against various cancer cell lines. The most potent compound displayed approximately 2.5 times greater activity compared to both reference compounds against ovarian cancer cell lines. These findings were supported by caspase-mediated apoptosis and molecular docking analyses. Docking revealed comparable VEGFR-2 affinities for 5b and 5-FU but highlighted stronger interaction of 5b with EGFR, evident from its lower docking score. Overall, these results signify the notable anti-proliferative potential of most synthesized hybrids, notably emphasizing the efficacy of compound 5b in suppressing cancer cell growth.

Effects of nitrate reduction on the biotransformation of 1H-1,2,4-triazole: Mechanism and community evolution.

Due to the refractory of 1 H-1,2,4-triazole (TZ), conventional anaerobic biological treatment technology is usually restricted by low removal efficiency and poor system stability. In this study, TZ biodegradation and nitrate reduction was coupled to improve the removal efficiency of TZ from polluted wastewater. Batch assay was performed with pure culture strain Raoultella sp. NJUST42, which was reported to have the capability to degrade TZ in our previous study. Based on batch assay result, complete removal of TZ could be achieved in the presence of nitrate, whereas only 50% of TZ could be removed in the control system. Long-term stability experiment indicated that the relative abundance of microorganisms (Bacteroidetes_vadinHA17, Georgenia, Anaerolinea, etc) was obviously enhanced under nitrate reduction condition. During long-term period, major intermediates for TZ biodegradation such as [1,2,4]Triazolidine-3,5-diol, hydrazine dibasic carboxylic acid and carbamic acid were detected. A novel TZ biotransformation approach via hydration, TZ-ring cleavage, deamination and oxidation was speculated. PICRUSt1 and KEGG pathway analyses indicated that hydration (dch), oxidation (adhD, oah, pucG, fdhA) of TZ and nitrate reduction (Nar, napA, nrfA, nirBK, norB, nosZ) were significantly enhanced in the presence of nitrate. Moreover, the significant enrichment of TCA cycle (gab, sdh, fum, etc.) indicated that carbon and energy metabolism were facilitated with the addition of nitrate, thus improved TZ catabolism. The proposed mechanism demonstrated that TZ biodegradation coupled with nitrate reduction would be a promising approach for efficient treatment of wastewater contaminated by TZ.

Easy and fast synthesis of MnCo-LDH yolk-shell spheres porous composites applied electrospinning nanofibers highly effective for extracting triazole fungicides.

Today, the wide utilization of triazole fungicides due to environmental damage and its side effects has raised global concern. Thus, in this investigation, polyacrylonitrile/MnCo-layered double hydroxides nanofiber was synthesized and applied as an effective and novel adsorbent at thin-film solid-phase micro-extraction technique for the quick and concurrent extraction of five triazole fungicides in fruit and vegetable samples before quantitative analysis by high-performance liquid chromatography-ultraviolet. The incorporation of MnCo-layered double hydroxides with porous structure and abundant functional groups in a polymer medium improves the extraction efficiency of nanofibers owing to hydrogen bonding and π-π interactions formed between analytes and synthesized nano-adsorbent. Various important elements that affect the extraction efficiency of the intended analytes were optimized using a time-variable approach. Under the optimum conditions, the limit of detection and quantification range from 0.1 to 0.15 and 0.3-0.5 ng mL-1, respectively.

Synthesis and crystal structure of an iron triazole complex resulting from the unexpected ligand cleavage of a triazolium carbene precursor.

Typically reactions of N-heterocyclic carbenes with transition metals are straightforward and require a carbene salt, a base strong enough to deprotonate such a salt and a metal. Yet when carbene precursors are in the form of triazolium salts, reaction may not proceed as easily as expected. In our work, we intended to obtain a triazolylidene complex of iron(II) chloride, but due to the presence of small amounts of water in the tetrahydrofuran solvent used, bis(acetonitrile)tetrakis(1-benzyl-1H-1,2,4-triazole-κN4)iron(II) µ-oxido-bis[trichloridoferrate(III)] acetonitrile disolvate, [Fe(C9H9N3)4(CH3CN)2][Fe2Cl6O]·2CH3CN - an interesting anion with a linear geometry of the O atom - was formed instead of the iron carbene complex. Reaction proceeded via cleavage of the alkyl N-substituent of the triazolium salt. The formation of the product was confirmed by X-ray crystallography. The crystal structure and possible reaction pathways are discussed.

Azole resistance mechanisms and population structure of the human pathogen Aspergillus fumigatus on retail plant products.

Aspergillus fumigatus is a ubiquitous saprotroph and human-pathogenic fungus that is life-threatening to the immunocompromised. Triazole-resistant A. fumigatus was found in patients without prior treatment with azoles, leading researchers to conclude that resistance had developed in agricultural environments where azoles are used against plant pathogens. Previous studies have documented azole-resistant A. fumigatus across agricultural environments, but few have looked at retail plant products. Our objectives were to determine if azole-resistant A. fumigatus is prevalent in retail plant products produced in the United States (U.S.), as well as to identify the resistance mechanism(s) and population genetic structure of these isolates. Five hundred twenty-five isolates were collected from retail plant products and screened for azole resistance. Twenty-four isolates collected from compost, soil, flower bulbs, and raw peanuts were pan-azole resistant. These isolates had the TR34/L98H, TR46/Y121F/T289A, G448S, and H147Y cyp51A alleles, all known to underly pan-azole resistance, as well as WT alleles, suggesting that non-cyp51A mechanisms contribute to pan-azole resistance in these isolates. Minimum spanning networks showed two lineages containing isolates with TR alleles or the F46Y/M172V/E427K allele, and discriminant analysis of principle components identified three primary clusters. This is consistent with previous studies detecting three clades of A. fumigatus and identifying pan-azole-resistant isolates with TR alleles in a single clade. We found pan-azole resistance in U.S. retail plant products, particularly compost and flower bulbs, which indicates a risk of exposure to these products for susceptible populations and that highly resistant isolates are likely distributed worldwide on these products.IMPORTANCEAspergillus fumigatus has recently been designated as a critical fungal pathogen by the World Health Organization. It is most deadly to people with compromised immune systems, and with the emergence of antifungal resistance to multiple azole drugs, this disease carries a nearly 100% fatality rate without treatment or if isolates are resistant to the drugs used to treat the disease. It is important to determine the relatedness and origins of resistant A. fumigatus isolates in the environment, including plant-based retail products, so that factors promoting the development and propagation of resistant isolates can be identified.

Discovery of gefitinib-1,2,3-triazole derivatives against lung cancer via inducing apoptosis and inhibiting the colony formation.

A series of 20 novel gefitinib derivatives incorporating the 1,2,3-triazole moiety were designed and synthesized. The synthesized compounds were evaluated for their potential anticancer activity against EGFR wild-type human non-small cell lung cancer cells (NCI-H1299, A549) and human lung adenocarcinoma cells (NCI-H1437) as non-small cell lung cancer. In comparison to gefitinib, Initial biological assessments revealed that several compounds exhibited potent anti-proliferative activity against these cancer cell lines. Notably, compounds 7a and 7j demonstrated the most pronounced effects, with an IC50 value of 3.94 ± 0.17 µmol L-1 (NCI-H1299), 3.16 ± 0.11 µmol L-1 (A549), and 1.83 ± 0.13 µmol L-1 (NCI-H1437) for 7a, and an IC50 value of 3.84 ± 0.22 µmol L-1 (NCI-H1299), 3.86 ± 0.38 µmol L-1 (A549), and 1.69 ± 0.25 µmol L-1 (NCI-H1437) for 7j. These two compounds could inhibit the colony formation and migration ability of H1299 cells, and induce apoptosis in H1299 cells. Acute toxicity experiments on mice demonstrated that compound 7a exhibited low toxicity in mice. Based on these results, it is proposed that 7a and 7j could potentially be developed as novel drugs for the treatment of lung cancer.

Bergofungin D, a peptaibol template for the introduction of chemical modifications, synthesis of analogs and comparative studies of their structures.

Bergofungin D is a helical peptide of the peptaibol family consisting of 14 amino acids, six of which are the helix inducer aminoisobutyric acid (Aib). In the second third of the sequence, a hydroxyproline causes a bending of the helix and a disruption of the hydrogen bond network, and Aib7 is the only amino acid in this region involved in the hydrogen bond network. Therefore, modification of this residue can serve as a probe to monitor the effect of introducing amino acid substitutions on this more fragile helical turn. To validate this approach, we simplified the original bergofungin D by reducing the number of non-classical amino acids, replacing the (R)-isovaleric acid by its enantiomer or an Aib and the hydroxyproline with a proline, respectively, without affecting its secondary structure. Within the modified structure, we replaced Aib7-Aib8 by its 1,2,3-triazolodipeptide equivalent or Aib7 by a serine or a dehydrobutyrine. We have reported and analyzed five crystal structures, three of which are new, demonstrating the usefulness of the modified bergofungin D as a probe for monitoring the introduction of amino acid substitutions within a helical structure.

Water-Soluble Quaternary and Protonable Basic Chitotriazolans: Synthesis by Click Chemistry Conversion of Chitosan Azides and Investigation of Antibacterial Activity.

The azide transfer reaction and copper(I)-catalyzed alkyne-azide cycloaddition (CuAAC) can be used to convert the amino groups in chitosan to triazole 1,2,3-moieties. The resulting polymer has been named chitotriazolan. This synthesis was performed with six different quaternary ammonium alkynes and three amine alkynes to obtain a series of nine water-soluble chitotriazolan derivatives. The structure and complete conversion of the azide were confirmed by FT-IR and proton NMR spectroscopy. The derivatives were investigated for antibacterial activity against S. aureus, E. faecalis, E. coli, and P. aeruginosa. The activity of the quaternized chitotriazolan derivatives varied depending on the structure of the quaternary moiety and the species of bacteria. The basic protonable derivatives were less active or inactive against the bacteria.

Design, Synthesis and In vitro Antitubercular Effect of New Chalcone Derivatives Coupled with 1,2,3-Triazoles: A Computational Docking Techniques.

A very interesting foundation for this study is the creation of new methods for modifying compounds with a 1,2,3-triazole and chalcone scaffolds, as these compounds are significant in organic synthesis, particularly in the synthesis of bioactive organic compounds. To contribute to the development of an efficient method for the conversion of antimicrobial and antituberculosis heterocyclics, a novel series of cyclohepta pyridinone fused 1,2,3-triazolyl chalcones were designed and synthesized. All the newly prepared scaffolds were characterized by FT-IR, NMR (1H & 13C) and mass spectrometry. Among the tested compounds, hybrids 8b, 8d, and 8f exhibited exceptional antibacterial susceptibilities with zone of inhibition 27.84±0.04, 32.27±0.02, and 38.26±0.01 mm against the tested E. faecalis bacteria, whereas 8d had better antitubercular potency against M. tuberculosis H37Rv strain with MIC value 5.25 µg/mL, compared to Streptomycin [MIC=5.01 µg/mL]. All the synthesized compounds were initially assessed in silico against the targeted protein i. e., DprE1 that indicated compound 8d, 8f and 8h along with several other 1,2,3-triazole compounds as possible inhibitors. Based on docking results, 8d showed that the amino acids His74(A), Lys76(A), Cys332(A), Asp331(A), Val307(A), Tyr357(A), Met226(A), Gln276(A), Gly75(A), Peo58(A), Leu259(A), and Lys309(A) exhibited highly stable binding to DprE1 receptor of Mycobacterium tuberculosis (PDB: 4G3 U). Moreover, these scaffolds physicochemical characteristics, filtration molecular properties, assessment of toxicity, and bioactivity scores were assessed in relation to ADME (absorption, distribution, metabolism, and excretion).

Copper-Catalyzed Synthesis of 4-CF3-1,2,3-Triazoles: An Efficient and Facile Approach via Click Reaction.

Incorporation of a trifluoromethyl group with 1,2,3-triazoles motifs was described. We explored a click reaction approach for regioselective synthesis of 1-susbstituted-4-trifluoromethyl-1,2,3-triazoles in which 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) reacts with commercial 2-bromo-3,3,3-trifluoropropene (BTP) to form 3,3,3-trifloropropyne (TFP) in situ. Arising from merits associated with the availability and stability of BTP, and the high efficiencies of CuI/1,10-Phenanthroline (Phen)-catalyzed cycloaddition reactions of azides with alkynes, this readily performed click process takes place to form the target 1,2,3-triazoles in high yields, and with a wide azide substrate scope. The potential value of this protocol was demonstrated by its application to a gram-scale reaction.

Quick synthesis of CoFe-PBA@GO with electrochemical method as a novel, sensitive, and degradable nanocomposite applied in nanofibers for triazole extraction before HPLC-UV analysis.

Today, the wide use of triazole fungicides due to environmental damage and its side effects has raised global concern. Hence, in this research, poly-vinyl alcohol/polyacrylic-acid/CoFe-PBA@GO electrospun nanofiber was synthesized and applied as effective, degradable, and novel adsorbent at pipette-tip microextraction (PT-µSPE) method for the rapid and concurrent extraction of five of triazole fungicides in fruit and vegetable samples prior to quantitative analysis by high-performance liquid chromatography-ultraviolet. The incorporation of CoFe-PBA@GO with superporous structure and abundant functional groups in a polymer medium improves the extraction efficiency of nanofibers due to hydrogen bonding and π-π interactions formed between analytes and synthesized nano-adsorbent. Various important elements that affect the extraction yield of the target analytes were optimized utilizing a time-variable approach. Under the optimum conditions, dynamic range was attained in the range of 0.3-900.0 ng/mL with correlation coefficients ≥ 0.999. The identification limit of the PT-µSPE-HPLC-UV method ranged from 0.1 to 0.3 ng/mL.