Pyridine Research Articles

Towards the synthesis of a 2-deoxy-2-fluoro-d-mannose building block and characterisation of an unusual 2-S-phenyl anomeric pyridinium triflate salt via 1 → 2 S-migration

Regio- and stereo-selective synthetic routes to 2-deoxy-2-fluoro-d-mannose building blocks are often experimentally challenging when using Selectfluor with the corresponding glycal. We targeted a late-stage method to introduce fluorine in a stereospecific manner using inversion via a triflate. Accordingly, synthesis of a conventionally protected 2-deoxy-2-fluoro-d-mannose β-thioglycoside donor, directly applicable to oligosaccharide synthesis, was attempted using C2-triflate inversion of the corresponding d-glucoside with TBAF. Unexpectedly, an anomeric pyridinium salt was isolated when attempting to form the C2-triflate using Tf2O in pyridine. Indicatively, this proceeds via a 1 → 2 S-migration delivering a 1,2-trans product with α-d-manno configuration and the anomeric pyridinium in a pseudo-equatorial position. The structure of this unexpected intermediate was confirmed in the solid-state using X-ray crystallography. Omission of the pyridine solvent led to dimer formation. Switching the aglycone to an O-para-methoxyphenyl enabled smooth C2 inversion to the desired 2-deoxy-2-fluoro d-mannose system, suitably equipped for further anomeric manipulation.

One-Pot Stereoselective Synthesis of the Naphthofurano-Iminosugars via a [3 + 2] Cycloaddition Reaction.

This study presents the synthesis of novel naphthofurano-iminosugars (4) using 2,3-O-isopropylidene D-ribose tosylate (1a), anilines (2), and 1,4-benzoquinone (3a) as starting materials through key iminium ion/enamine intermediates via [3 + 2] cyclization reactions at room temperature. The reaction has unique regioselectivity and stereoselectivity with moderate to excellent yields. The adaptability of this method has been demonstrated using various substituted anilines, on which both electron-donating and electron-withdrawing groups were well employed in the reactions. Notably, the treatment of the fused multicyclic iminosugar 4 with TFA efficiently leads to an interesting unexpected pyridinium salt (8), possible via four sequential steps: deprotection of the 2,3-O-isopropylidene group, furan ring opening, dehydration condensation of the OH groups, and elimination of water.

Homoleptic chromium(II) aminopyridinates: Transoid vs cisoid coordination

Rare homoleptic divalent chromium complexes have been isolated by reacting two equivalents of sterically bulky deprotonated 2–aminopyridine ligands, N–(2,4,6–trimethylphenyl)–[6–(2,4,6–trimethylphenyl)–pyridine–2–yl]–amine (1), N–(2,6–diisopropylphenyl)–[6–(2,6–dimethylphenyl)–pyridine–2–yl]–amine (2) and N–(2,6–diisopropylphenyl)–[6–(2,4,6–trimethylphenyl)–pyridine–2–yl]–amine (3) with CrCl2 in tetrahydrofuran (THF). Reaction of deprotonated 1 proceeds smoothly at room temperature while that of sterically more bulky 2 and 3 at reflux temperature. The respective bis(aminopyridinate) Cr complexes (4–6) are monomeric and show different orientations of the coordinated ligands. For compound 5, two isomers were identified. For 4 and 5a the two ligands show head to tail arrangement while in 5b and 6 the two ligands adopt the unknown head to head arrangement of aminopyridinato ligands. All the complexes show distorted square planar geometries around the chromium center. For 4 and 5a in which the ligands are coordinated in transoid manner the pyridine rings and amido nitrogen atom lie in the coordination plane of chromium. Hirshfeld analyses showed that H∙∙∙H and H∙∙∙C/C∙∙∙H π–interactions were the main and at times the strongest contributions for the intermolecular interactions.

Synthetic and theoretical study on novel N-ylidic complexes of mercury as new antibacterial agents

The novel structure of Hg(II) complexes including the pyridinium ylide C5H5NCHC(O)C6H4-m-Br (Y) were synthesized and reported in this study. In the first step, the pyridinium salt C5H5NCH2C(O)C6H4-m-Br (S) was produced by reacting 2,3′-dibromoactophenone and pyridine. then, treatment of S with K2CO3 gave the related pyridinium ylide Y. Finally, the reaction of Y with HgX2 and Hg(NO3)2·H2O leads to the formation of novel binuclear [HgY2][HgX4] (X=Cl (1); X=Br (2); X=I (3)) and polymeric [HgY(NO3)2]n (4) complexes. The structure of complex 2 was also determined by X-ray diffraction analysis. The obtained analyses proved the coordination through the ylidic carbon to metallic center. Additionally, Natural Bond Orbital (NBO), Energy Decomposition Analysis (EDA), and EDA-NOCV studies are also used to investigate the nature of metal–ligand bonding in the complexes. Finally, the antibacterial activity of 1–4 was also examined against Gram positive and negative represented significant levels of inhibitory potency respected to used standards.

Grignard Reagent Addition to Pyridinium Salts: A Catalytic Approach to Chiral 1,4-Dihydropyridines.

Catalytic dearomatization of pyridinium salts is a powerful technique for constructing chiral N-heterocycles, which are crucial in alkaloid natural products and drugs. Despite its potential, progress in metal-catalyzed asymmetric dearomatization of pyridinium derivatives has been limited. Here, we present the enantioselective 1,4-dearomatization of pyridinium salts using Grignard reagents and chiral copper catalysis. This approach yields enantioenriched functionalized 1,4-dihydropyridines. Experimental kinetic isotope effects and density functional theory calculations provide insights into the reaction mechanism, regio- and enantioselectivity, and the rate-limiting step.

Synthesis and structural elucidation of novel quaternary pyridinium salt and indolizine derivatives as an anti-tubercular agent: In Silico and In Vitro screening

The in vitro anti-mycobacterial activity of a novel series of diversely substituted quaternary pyridinium salts (3a-m) and indolizines (5a-h) were assessed against H37Rv strain of Mycobacterium tuberculosis (M.tb). The series of intermediate 1-(2-oxo-2-phenylethyl)-4-(piperidin-1-yl)pyridin-1-ium bromide, which contains a heterocyclic ring molecule, has been prepared by reacting with 4-(piperidin-1-yl)pyridine and phenacyl bromide at room temperature. The final ethyl 3-benzoyl-7-(piperidin-1-yl)indolizine-1-carboxylate analogues were prepared by using pyridin-1-ium bromide with electron-deficient acetylene, undergoing 1, 3-dipolar cycloaddition at the ambient temperature using anhydrous potassium carbonate and N, N-dimethylformamide as a solvent. All the newly synthesized compounds were characterized by spectroscopic techniques such as 1H and 13C NMR, and HRMS. All the synthesized intermediates and final compounds were evaluated for their anti-tubercular activities against H37Rv (ATCC 27294) strain. All the compounds exhibited anti-tubercular activities in the range of 12.5–50 µM. In vitro screening of all derivatives concluded that among all the screened candidates 3k emerged as an active hit with MIC 12.5 µM, 3l and 3m with MIC 25 µM.

Copolymerization of novel self-promoted curing phthalonitrile with epoxy resin and its thermal property

The disadvantage of poor thermal performance of epoxy resin limits its application in special fields, therefore we improve the thermal performance of epoxy resin by copolymerizing it with phthalonitrile resin. A novel self-promoted curing phthalonitrile monomer containing pyridine rings and amino groups (APNH) was successfully synthesized using 2-amino-4-hydroxypyridine and 4-nitrophthalonitril, and characterized by FTIR and NMR spectra. DSC confirmed that the APNH monomer exhibits curing behavior that is self-promoting. Copolymerizing the APNH monomer with epoxy resin enhances the thermal performance of the epoxy resin. The curing behavior of the EPNH copolymer was studied using DSC, which revealed two distinct curing peaks. FTIR analysis showed that the EPNH copolymer has formed structures such as triazine, phthalocyanine, and isoindoline. The presence of cyano groups significantly enhances the thermal properties of the copolymer, surpassing those of traditional epoxy resins. This enhancement in thermal performance amplifies with an increase in the content of the APNH monomer. The research indicates that the EPNH copolymer exhibits superior thermal stability and elevated glass transition temperatures, facilitating the application of epoxy resin in specialized areas.

Analysis of volatile flavor compounds in Antarctic krill paste with different processing methods based on GC-IMS.

In this study, shrimp paste was prepared using Antarctic krill and fermented Antarctic krill shrimp paste as raw materials. Two commonly used heating methods, stir-fried and steaming, were analyzed, the main difference between the two methods being that stir-frying involves putting the shrimp paste into a wok and stir-frying it for different periods of time, while steaming involves putting the shrimp paste into a steamer and steaming it for different periods of time. The effects of different salt concentrations and processing techniques on the volatile flavor compounds of shrimp paste were also observed. Electronic nose and gas chromatography-ion mobility spectrometry (GC-IMS) were employed to analyze the volatile flavor compounds. A total of 52 volatile flavor compounds were detected by GC-IMS, of which 38 were identified (including monomers, dimers, and polymers). The identified compounds included 11 aldehydes, 6 ketones, 14 alcohols, 2 esters, 2 acids, 1 pyridine compound, and 2 sulfur compounds. In addition, 14 compounds were identifiable. Using the results of the electronic nose analysis, we were also able to differentiate between the volatile flavor compounds in shrimp pastes produced by different processing methods.

Aggregation-induced emission-based competitive immunoassays for “signal-on” detection of proteins with multifunctional metal–organic frameworks as signal tags

An aggregation-induced emission (AIE)-based strategy was proposed for fluorescence immunoassays of protein biomarkers using Cu-based metal–organic frameworks (Cu-MOFs) to load recombinant targets and enzymes for dual signal amplification. The immunosensing platform was built based on the sequestration and consumption of the substrates of pyrophosphate (PPi) ions by Cu-MOFs and enzymatic catalysis. The negatively charged PPi could trigger the aggregation of positively charged tetraphenylethene (TPE)-substituted pyridinium salt nanoparticles (TPE-Py NPs) by electrostatic interactions, lighting up the fluorescence due to the AIE phenomenon. The consumption of PPi by the captured Cu-MOFs through the Cu2+-PPi chelation interaction and ALP–enzymatic hydrolysis depressed the aggregation of TPE-Py NPs. Capture of the tested targets in samples by the antibodies on the plate surface could prevent the attachment of target/ALP-loaded Cu-MOFs due to the competitive immunoreactions. The “signal-on” competitive immunoassay was applied for the detection of procalcitonin (PCT) as the model analyte with a linear range of 0.01–10 pg/mL and a detection limit down to 8 pg/mL. The conceptual integration of AIE with enzymatic and MOFs–based dual signal amplification endowed fluorescence immunoassays with high sensitivity and selectivity. The surface modification of Cu-MOFs with hexahistine (His6)-tagged recombinant proteins through metal coordination interactions should be evaluable for the design of novel biosensors.

Structure-based discovery of a 4,5-Dihydropyrazole-cored PET ligand for imaging of receptor-interacting serine/threonine-protein kinase 1 (RIPK1) in the brain

Receptor-interacting serine/threonine-protein kinase 1 (RIPK1) regulates programmed cell death and inflammation, contributing to a wide range of human pathologies, including inflammatory disorders, neurodegenerative conditions, and cancer. Despite this, no RIPK1 positron emission tomography (PET) ligand with significant in vivo specificity has been reported to date. In this work, we designed and synthesized a new family of dihydropyrazole-cored ligands suitable for 18F-labeling at the late stage. Among these, WL8 showed a strong binding affinity to RIPK1 (EC50 = 19.9 nM, Kd = 25 nM) and was successfully labeled with 18F in the 6-position of pyridine ring, yielding a high radiochemistry yield of 27.9 % (decay-corrected) and a high molar activity of 18.8–31.2 GBq/μmol. In in vitro autoradiography, [18F]WL8 showed some specific binding in the brain sections of rats and lipopolysaccharide (LPS) model mice. Preliminary PET studies in rat brains revealed that [18F]WL8 could efficiently penetrate the blood-brain barrier and was rapidly washed out. As anticipated, [18F]WL8 exhibited a high initial uptake (brain2min = 4.80 % ID/g) in mouse brains, followed by a rapid washout (brain60min = 0.14 % ID/g), although no clear specific binding to RIPK1 was observed. Moderate in vivo stability was noted for [18F]WL8 in mouse brains with 35.2 % of the parent fraction remaining after 30 min post-administration. Altogether, our work broadens the landscape and offers a new chemotype for RIPK1 PET ligand development.

The structural basis of pyridoxal-5′-phosphate-dependent β-NAD-alkylating enzymes

SbzP is a unique pyridoxal-5′-phosphate-dependent enzyme, which catalyses a [3+2] annulation between the pyridinium ring of β-nicotinamide adenine dinucleotide (β-NAD) and an electron rich β,γ-unsaturated quinonoid derived from S-adenosylmethionine in natural product azaindane antibiotics biosynthesis. The SbzP-mediated annulation has been proposed to be a rare tandem C–C bond formation, but its structural basis and catalytic mechanism remain largely unknown. Here we report the β-NAD-complexed structure of PseP (SbzP homologue), identified by cryo-electron microscopy. Structure-based mutagenesis, stopped-flow analysis, thermal shift and surface plasmon resonance analysis identified the important residues for the substrate binding. Molecular dynamics simulations provided insights regarding how the enzyme orients the Cγ of the unsaturated quinonoid to β-NAD. In addition, density functional theory calculations confirmed that the proposed stepwise mechanism is more likely than a pericyclization mechanism. This study provides the structural basis of a pyridoxal-5′-phosphate-dependent enzyme that catalyses nucleophilic Cγ addition and β-NAD processing in natural product biosynthesis.

A polymeric Co(II) oxalate salt containing pyridinium type cations: Synthesis, structure, spectroscopy, thermal behavior and magnetism

A Co(II) oxalate coordination polymer, (C7H11N2)2[Co(C2O4)2]·5H2O (1) (C7H11N2+ = 2-amino-4,6-dimethylpyridinium cation), has been synthesized and characterized by elemental and thermal analyses, FT-IR and UV/Vis spectroscopies, powder X-ray diffraction (PXRD), single-crystal X-ray diffraction and variable temperature magnetic susceptibility measurements. Compound 1 is a polymerized organic–inorganic hybrid salt, the asymmetric unit of which consists of one Co(II) ion, one bidentate C2O42− ligand, two halves of bidentate C2O42− ligands, two 2-amino-4,6-dimethylpyridinium C7H11N2+ cations and five crystal water molecules. Each CoII center is six-coordinated in a distorted octahedral geometry fulfilled by six oxygen atoms from three chelating C2O42− ligands. The [Co(C2O4)2]2− ions act as complex ligands and efficiently bridge neighboring Co2+ ions, forming chains of complex anions linked by hydrogen bonded water molecules. Hydrogen bonding interactions of the type OH∙∙∙O and NH∙∙∙O along with π–π stacking interactions between pyridine rings contribute to the stabilization of the 3D supramolecular framework. Temperature-dependence magnetic moment (µ) collected under zero-field cooled (ZFC) and field-cooled (FC) conditions revealed weak antiferromagnetic ordering at low temperatures.

Current Market Potential and Prospects of Copper-based Pyridine Derivatives: A Review.

Nicotine, minodronic acid, nicotinamide (niacin), zolpidem, zolimidine, and other pyridine-based chemicals play vital roles in medicine and biology. Pyridinecontaining drugs are widely available on the market to treat a wide range of human ailments. As a result of these advances, pyridine research is continually expanding, and there are now higher expectations for how it may aid in the treatment of numerous ailments. This evaluation incorporates data acquired from sources, like PubMed, to provide a thorough summary of the approved drugs and bioactivity data for compounds containing pyridine. Most of the reactions discussed in this article will provide readers with a deeper understanding of various pyridine-related examples, which is necessary for the creation of copper catalysis-based synthetic processes that are more accessible, secure, environmentally friendly, and practical, and that also have higher accuracy and selectivity. This paper also discusses significant innovations in the multi-component copper-catalyzed synthesis of N-heterocycles (pyridine), with the aim of developing precise, cost-effective, and environmentally friendly oxygenation and oxidation synthetic methods for the future synthesis of additional novel pyridine base analogs. Therefore, the review article will serve as a novel platform for researchers investigating copperbased pyridine compounds.

Highly Anion‐Conductive Viologen‐Based Two‐Dimensional Polymer Membranes as Nanopower Generators

AbstractTwo‐dimensional polymers (2DPs) and their layer‐stacked 2D covalent organic frameworks (2D COFs) membranes hold great potential for harvesting sustainable osmotic energy. The nascent research has yet to simultaneously achieve high ionic flux and selectivity, primarily due to inefficient ion transport dynamics. This is directly related to ultrasmall pore size (<3 nm), much smaller than the duple Debye length in the diluted electrolyte (6–20 nm), as well as low charge density (<4.5 mC m−2). Here, we introduce a π‐conjugated viologen‐based 2DP (V2DP) membrane possessing a large pore size of 4.5 nm, strategically enhancing the overlapping of the electric double layer, coupled with an exceptional positive surface charge density (~6 mC m−2). These characteristics enable the membrane to facilitate high anion flux while maintaining ideal selectivity. Notably, V2DP membranes realize an impressive current density of 5.5×103 A m−2, surpassing benchmarks set by previously reported nanofluidic membranes. In the practical application scenario involving the mixing of artificial seawater and river water, the V2DP membranes exhibit a considerable ion transference number of 0.70 towards Cl−, contributing to an outstanding power density of ~55 W m−2. Theoretical calculations reveal the important role of the large quantity of anion transport sites, which act as binding sites evenly located in the positively charged N‐containing pyridine rings. These binding sites enable kinematic coupling and decoupling between anions and the V2DP skeleton, establishing a continuous Cl− ion transport pathway. This work demonstrates the great promise of large‐area ultrathin 2DP membranes featuring highly organized charged ion transport networks when applied for osmotic energy conversion.

Reductive alkyl-alkyl coupling from isolable nickel-alkyl complexes.

The selective cross-coupling of two alkyl electrophiles to construct complex molecules remains a challenge in organic synthesis1,2. Known reactions are optimized for specific electrophiles and are not amenable to interchangeably varying electrophilic substrates that are sourced from common alkyl building blocks, such as amines, carboxylic acids and halides3-5. These limitations restrict the types of alkyl substrate that can be modified and, ultimately, the chemical space that can be explored6. Here we report a general solution to these limitations that enables a combinatorial approach to alkyl-alkyl cross-coupling reactions. This methodology relies on the discovery of unusually persistent Ni(alkyl) complexes that can be formed directly by oxidative addition of alkyl halides, redox-active esters or pyridinium salts. The resulting alkyl complexes can be isolated or directly telescoped to couple with a second alkyl electrophile, which represent cross-selective reactions that were previously unknown. The utility of this synthetic capability is showcased in the rapid diversification of amino acids, natural products, pharmaceuticals and drug-like building blocks by various combinations of dehalogenative, decarboxylative or deaminative coupling. In addition to a robust scope, this work provides insights into the organometallic chemistry of synthetically relevant Ni(alkyl) complexes through crystallographic analysis, stereochemical probes and spectroscopic studies.

1,2-Amidoarylcarbonylation of Styrenes to Access β-Acylamino Ketones by NHC-Catalyzed Radical Relay.

An amidoarylcarbonylation reaction of aromatic aldehydes and olefins with Katritzky pyridinium salts by N-heterocyclic carbene (NHC)-catalyzed radical relay to construct C-C and C-N bonds with good functional group tolerance is developed for the synthesis of β-acylamino ketones. This gentle and efficient approach offers a valuable style for the synthesis of β-acylamino ketones. Mechanistic studies revealed that a radical addition/coupling/elimination cascade process was involved in this reaction.

Direct C4 and C2 C-H Amination of Heteroarenes Using I(III) Reagents via a Cross Azine Coupling.

Aminated nitrogen heterocycles are valuable motifs across numerous chemical industries, perhaps most notably in small molecule drug discovery. While numerous strategies for installing nitrogen atoms onto azaarenes exist, most require prefunctionalization and methods for direct C-H amination are almost entirely limited to position C2. Herein, we report a method for the direct C2 and C4 C-H amination of fused azaarenes via in situ activation with a bispyridine-ligated I(III) reagent, [(Py)2IPh]2OTf, or Py-HVI. Unlike commonly used N-oxide chemistry, the method requires no preoxidation of the azaarene and provides unprecedented direct access to C4 amination products. The resulting N-heterocyclic pyridinium salts can be isolated via simple trituration. The free amine can be liberated under mild Zincke aminolysis, or the amination and cleavage can be telescoped to a one-pot process. The scope of the method is broad; the conditions are mild and operationally simple, and the aminated products are produced in good to excellent yields. Computational studies provide insights into the mechanism of activation, which involves an unusual direct nucleophilic functionalization of an I(III) ligand, as well as a kinetic basis for the observed C2 and C4 amination products.

Evaluation of 3, 3’-Disubstituted Oxindoles Derivatives as a Potential Anti- Cancer Tyrosine Kinase Inhibitors-molecular Docking and ADME Studies

Aim: This study aims to explore the binding interactions between synthesized 3,3’-Disubstituted Oxindoles and the HCK enzyme, with the specific goal of discovering potential anticancer agents. Background: Cancer presents an ongoing global health challenge, necessitating the exploration of innovative therapeutic approaches. Isatin derivatives and pyridine compounds hold great promise for the development of anticancer drugs due to their wide-ranging biological activities. Moreover, HCK plays a significant role in chemotherapy resistance and reduced drug efficacy in clinical settings, highlighting its importance in the intricate network of cancer pathophysiology. There is an urgent need for targeted interventions to regulate HCK activity and enhance cancer treatment outcomes. Methods: In our study, we ensured meticulous optimization of protein and ligand preparation to guarantee accurate docking simulations. We conducted molecular docking analyses using the state-of-the-art Glide module and assessed ADME properties using the Schrödinger suite's QikProp tool. Results: Through molecular docking, compounds 3c and 3e have emerged as promising anticancer agents with low docking scores against Tyrosine Kinase. Further ADME analysis has provided valuable insights into the compounds' in-silico behaviour, while computed dipole moments have enhanced our understanding of their physicochemical characteristics Conclusion: In this study, we explored how the synthesized compounds bind within the HCK active site, indicating potential anticancer properties. Through in silico docking, we identified compounds 3c and 3e as possible anticancer agents, with the lowest docking scores of -7.621 and -7.602 kcal/mol against Tyrosine Kinase. These findings emphasize the importance of computational approaches in drug discovery and offer valuable insights for future research and development efforts.

Specific adsorption of antiviral drugs on ionic liquid-modified metal–organic framework: Adsorption behavior, mechanism, and DFT analysis

As emerging contaminants, antiviral drugs (ATVs) in water pose an increasing threat to human health and the ecosystem. Using specific and selective adsorption methods to remove ATVs remains challenging due to their trace concentration in real matrices. In this study, pyridine ionic liquid ([BPy][Sal])-modified metal–organic framework (MOF), a type of novel material, was synthesized as [BPy][Sal]@MOF to adsorb ATVs with different molecular structures, i.e., Arbidol (Arb) and Favipiravir (Fav). Arb adsorption followed the pseudo-second-order model, indicating that chemisorption is the dominant process. The Langmuir isothermal model showed that the maximum adsorption capacities toward Arb and Fav were 506.9 and 35.3 mg g−1, respectively, suggesting specific adsorption of Arb on [BPy][Sal]@MOF. Density functional theory (DFT) was used to investigate the specific adsorption mechanism. The molecular electrostatic potential and the intermolecular weak interaction analysis using the DFT method illustrated that the amino hydrogens in MOF could form hydrogen bonds (NHO) with the hydroxyl oxygens in Arb. Simultaneously, the indole ring in Arb could cause π–π interaction with the pyridine ring in [BPy][Sal] part from [BPy][Sal]@MOF. In contrast, the adsorption of Fav only involved π–π interaction between the benzene rings in Fav and the MOF part from [BPy][Sal]@MOF. The adsorption energy and energy gap calculation results verified that the adsorption strength of Arb was higher than that of Fav, and the key role of [BPy][Sal] in [BPy][Sal]@MOF helped achieve specific adsorption was confirmed. [BPy][Sal]@MOF exhibited exceptional recyclability after five adsorption–desorption cycles in environmental waters, demonstrating its excellent adsorption performance in practical applications.

Synthesis and Antimicrobial Activity of Newly Synthesized Nicotinamides.

Antioxidants are promising compounds with antimicrobial activity against drug-resistant pathogens, especially when combined with conventional antimicrobials. Our study aimed to characterize the structure of nicotinamides synthesized from nicotinic acid and thiocarbohydrazones and to evaluate their antibacterial and antifungal activity. Seven nicotinic acid hydrazides (NC 1-7) were synthesized using mono-thiocarbohydrazones with hydroxyl group substituents, along with quinolone, phenolic, and pyridine rings known for their antimicrobial activity. The in vitro antimicrobial activity of NC 1-7, at concentrations ranging from 0.001 to 1 mM, was tested against Staphylococcus aureus (ATCC 6538), Enterococcus faecalis (ATCC 29212), Pseudomonas aeruginosa (ATCC 27853), Klebsiella pneumoniae (NCIMB 9111), and Candida albicans (ATCC 24433) using the broth microdilution method per EUCAST 2024 guidelines. Microorganism survival percentages were calculated based on optical density, and target fishing using the PharmMapper database identified potential molecular targets. The results showed that P. aeruginosa was most susceptible to the compounds, while C. albicans was the least susceptible. NC 3 significantly inhibited P. aeruginosa and K. pneumoniae growth at 0.016 mM, while higher concentrations were required for S. aureus, E. faecalis, and C. albicans. NC 5 was most effective against gram-positive bacteria at 0.03 mM. Only NC 4 completely inhibited C. albicans below 1 mM. NC 3, with the lowest concentration for 50% growth inhibition (0.016-0.064 mM), showed promising antibacterial potential against specific AMR-related proteins (bleomycin resistance protein, HTH-type transcriptional regulator QacR, and streptogramin A acetyltransferase), suggesting that this class of compounds could enhance or restore the activity of established antibiotics.