Search Results (210)

Multicomponent reactions with isocyanides (IMCRs) enable the one-step assembly of complex molecules and remain a powerful strategy for accessing bioactive scaffolds. Here, we report the first synthesis of an abietane diterpene isocyanide derived from aminoimide methyl maleopimarate 1, a levopimaric acid-maleic anhydride adduct. This isocyanide was further engaged in Passerini, Ugi, and azido-Ugi reactions to provide a series of α-acyloxy- and α-acylaminocarboxamides, as well as tetrazoles, in high yields under optimized conditions. The structures of all products were confirmed by comprehensive physicochemical analysis. In silico ADME, drug-likeness, target prediction, and toxicity studies (SwissADME, ProTox-III) revealed moderate lipophilicity with favorable membrane permeability and solubility, high gastrointestinal absorption, and selective CYP3A4 inhibition with no significant effects on other CYP450 isoforms. The compounds fulfill major drug-likeness criteria, lacking undesirable reactive fragments, with only acceptable deviations in molecular weight and flexibility typical for MCR-derived products. The modifications broaden the spectrum of predicted biological targets while maintaining low overall toxicity and absence of predicted hepato- or carcinogenicity. These results demonstrate that diterpene isocyanide is a valuable building block for chemical libraries of structurally diverse abietane derivatives with peptide-like termini and highlight its potential as a source of cytotoxic, antiviral, and anti-inflammatory candidates. Full article

The development of new anti-inflammatory agents with improved safety and efficacy remains a major therapeutic challenge, particularly in light of the adverse effects associated with conventional nonsteroidal anti-inflammatory drugs. In this study, a series of new flavone derivatives were synthesized and evaluated for their inhibitory activities against Cyclooxygenase-1 (COX-1), Cyclooxygenase-2 (COX-2), and 5-Lipooxygenase (5-LOX) through combined in vitro and in silico approaches. Biological screening demonstrated that several derivatives exhibited moderate to strong inhibitory activity across the three enzymes, with IC₅₀ values ranging from 35.67 ± 2.92 to 1137.44 ± 371.05µM. Among these, compounds 5a and 5b emerged as the most promising dual COX-2/5-LOX inhibitors, displaying potent activity toward both targets while maintaining limited COX-1 inhibition, as reflected by their favorable selectivity indices (SI = 2.09 and 5.21, respectively). Molecular docking studies supported the experimental findings, revealing favorable binding affinities of compounds 5a and 5b within the COX-2 active site (PDB: 1CX2), while the flavone–tetrazole hybrid 6b exhibited the highest binding affinity toward the 5-LOX active site (PDB: 6N2W), consistent with its notable inhibitory activity. In silico ADME and toxicity predictions further suggested that the selected derivatives (4a-b, 5a-b, and 6a-b) possess acceptable physiochemical properties, low predicted toxicity, and favorable drug-likeness. Overall, this study identifies flavone-based scaffolds as a promising early-stage lead for the development of dual COX-2/5-LOX inhibitors and provides a rational basis for the design of safer anti-inflammatory agents. Full article

Vulvovaginal candidiasis (VVC) represents a widespread gynaecological challenge, affecting approximately 75% of women at some point during their reproductive years, with a significant subset progressing to recurrent forms (RVVC). Classical azoles and polyenes remain the cornerstone of therapy. However, their clinical utility is undermined by the rise of azole-resistant non-Candida albicans species, the capacity of Candida to form biofilms, and a complex variety of host-related factors that complicate disease expression and therapeutic response. This narrative review provides a critical up-to-date examination of the therapeutic landscape, integrating current diagnostic algorithms with pharmacological strategies for both acute, recalcitrant and recurrent VVCs. We assess the efficacy and safety of established antifungal agents alongside the breakthrough introduction of novel drug classes, with a particular interest in the oral triterpenoid ibrexafungerp and the tetrazole oteseconazole, which offer new mechanisms of action for cases that fail to respond to standard regimens. Furthermore, we address the management of a special clinical scenarios, including pregnancy and lactation, and explore promising emerging innovative approaches such as mucoadhesive formulations, immunomodulatory approaches, and alternative non-antifungal therapies. Ultimately, this review aims to support clinical decision-making by balancing the accessibility and user-friendliness of conventional treatments with the targeted precision offered by modern antifungal agents. Full article

Background/Objectives: Cephalosporins represent one of the most important classes of β-lactam antibiotics, widely used in clinical practice due to their broad-spectrum activity and favorable safety profile. As generations evolved, structural modifications were introduced to expand antimicrobial coverage and overcome β-lactamase resistance. This study aimed to analyze the drug-like properties of cephalosporins across different generations using molecular descriptors to identify structural and pharmacokinetic patterns influencing bioavailability and oral administration profiles. Methods: Thirty-eight cephalosporins representative of different generations were selected. Molecular data were obtained from PubChem, and SMILES were extracted and validated. Molecular descriptors (including MW, logP, TPSA, HBA, HBD, rotatable bonds, and global complexity indices) were calculated using the SwissADME and ChemDes platforms. Statistical analysis included ANOVA followed by post hoc tests, and principal component analysis (PCA). Results: A progressive increase in molecular weight, polarity, and TPSA was observed across generations, with fourth-generation cephalosporins showing significantly higher values compared to first-generation compounds (p < 0.0001). LogP decreased significantly in fourth-generation agents (p < 0.0001), reflecting increased polarity. PCA revealed that most compounds from generations 1–2 cluster in regions consistent with Lipinski’s and Veber’s rules, whereas fourth- and fifth generation - cephalosporins deviated substantially, prioritizing antimicrobial efficacy over oral bioavailability. Recurrent structural modifications such as oximes, tetrazoles, and aminothiazoles were identified, with increasing frequency in modern generations. Conclusions: The evolution of cephalosporins reflects a strategic shift toward enhanced antimicrobial potency and β-lactamase stability at the expense of oral bioavailability. Understanding these structural transitions provides valuable insights for rational drug design, aiming to balance antimicrobial effectiveness with favorable pharmacokinetic profiles essential for therapeutic success. Full article

2,3,5-triphenyl-2H-tetrazol-3-ium (TPT) chloride was studied through a combination of theoretical methods and experimental data, revealing structural and physical-chemical properties of the hydrate salt, [TPT]Cl·H₂O. The previously reported crystal structure was confirmed, but our study at lower T (100 K vs. 220 K) showed different positions for the two H₂O molecules in the unit cell around the chlorides. One of them (Cl1) is found surrounded by the tetrazole units, which we call the “dry pocket”, in contrast to the other, Cl2, which is involved in a hydrogen bonding cluster that consists of chloride and two water molecules, referred to as the “wet pocket”. Hirshfeld surface analyses showed predominant H⋯H interactions, followed by C⋯H interactions (including C–H⋯Cl/O interactions), and H⋯Cl contacts, which represent the C–H⋯Cl2 hydrogen bonds. Density functional theory (DFT) and (time-dependent) TD-DFT calculations on a molecular model of the compound, benchmarking the three functionals B3LYP, CAM-B3LYP, and PBE1PBE, found excellent agreement with experimental solution data when using the CAM-B3LYP function. UV-Vis absorptions observed at 320 nm, 245 nm, and 204 nm (in MeOH solution) were quite accurately reproduced and assigned. The observed bands were assigned to mixed HOMO–n⟶LUMO+m transitions, involving in all cases the LUMO+1 for the most intense band at 245 nm. Solid-state calculations on the GGA (PBE) level of theory using the CASTEP code and including the Tkatchenko–Scheffler (TS) scheme for the description of long-range interactions gave a good match for the calculated electronic band gap in the solid-state of 3.54 eV compared with the experimental value of 3.12 eV obtained through the Tauc plot method. Full article

This paper demonstrates the successful synthesis of novel hybrid heterogeneous catalysts for the sustainable conversion of CO₂ into cyclic organic carbonates (COCs). The nanocat-alysts have been fabricated by encapsulating pre-formed ultra-small gold nanostructures into a nascent zinc-coordination polymer (ZnCP) framework formed from two organic building blocks, 2,4-naphthalenedicarboxylic acid (1,4-NDC) and 5-amino-1H-tetrazole (5-Atz), which serves as a nitrogen-rich ligand. Applying the fabricated catalysts in the synthesis of COCs yields high yields (up to 97%) and high selectivity (up to 100%), with exceptionally high turnover frequencies (TOFs) (up to 408 h⁻¹). The catalytic process can be carried out under mild conditions (80 °C, 1.5 MPa CO₂) and without the use of solvents. Nitrogen-rich ligand molecules in the structure of ZnCPs enhance catalytic performance thanks to additional nucleophilic centres, which are effective in the epoxides’ ring-opening process. The hybrid catalysts with encapsulated gold nanostructures, which modify the liquid–gas interface between epoxide and CO₂, give significantly higher yields and TOFs for less active epoxides. The designed hybrid nanocatalysts exhibit superior stability under the studied reaction conditions and can be reused without loss of activity. The developed coordination polymers are constructed from green components, and green chemistry principles are applied to prepare these catalytic materials. Full article

1,5-disubstituted tetrazoles (1,5-Ds-T) are heterocyclic bioisosteres of the cis-amide bond, commonly found in bioactive compounds, pharmaceuticals, and functional materials. Chromones are privileged scaffolds widely present in natural products that are well known for their diverse biological activities, including anticancer, antimicrobial, antidiabetic, anti-inflammatory, and antioxidant properties. Isocyanide-based multicomponent reactions, such as the Ugi-Azide (UA-4CR), provide a versatile strategy for synthesizing 1,5-Ds-T, which can be incorporated into other privileged heterocyclic or commercially available drugs. Herein, we describe a sonochemical one-pot synthesis of 1,5-Ds-T connected to chromone under mild conditions, highlighting their potential relevance in medicinal chemistry. Full article

Innovative energy storage technologies in the energetic materials field represent a critical frontier in energy research. Consequently, we developed a performance regulation strategy based on tetrazolyl high-energy-density energy storage molecular systems and theoretically assessed their energetic properties and safety profiles. The findings reveal that substituent characteristics profoundly affect the performances of these energy storage molecular systems. The molecule systems ((1-amino-1H-tetrazol-5-yl)azanediyl)bis(1H-tetrazole-5,1-diyl) dinitrate, ((1-azido-1H-tetrazol-5-yl)azanediyl)bis(1H-tetrazole-5,1-diyl) dinitrate, ((1-nitro-1H-tetrazol-5-yl)azanediyl)bis(1H-tetrazole-5,1-diyl) dinitrate, and especially ((1-azido-1H-tetrazol-5-yl)azanediyl)bis(1H-tetrazole-5,1-diyl) dinitrate, exhibit exceptional performances, including high density, high heat of formation, high detonation velocity and pressure, zero oxygen balance, and low impact sensitivity, qualifying them as high-energy-density and low-sensitivity candidates. This work offers novel pathways for advancing energy storage technologies in energetic materials field. Full article

In this work, we report the effect of combining styrene-vinyl tetrazole copolymer (StVTz) and ammonium polyphosphate (APP) on the thermal degradation, mechanical properties, flame retardancy, and char formation of low-density polyethylene with ethyl vinyl acetate (LDPE/EVA) composites. The tetrazole heterocycle exhibits high thermal stability (>200 °C), and during its thermal decomposition, it releases non-toxic nitrogen gas. Its degradation generates reactive species capable of cross-linking the polymer chains, thereby promoting the formation of a protective char layer. To evaluate the influence of composition on the intumescent flame-retardant (IFR) properties of LDPE/EVA blends, different concentrations of APP and StVTz additives were incorporated. The composites were prepared in an internal mixer (Brabender Intelli-Torque Plasti-Corder). Test specimens were obtained by compression molding and subsequently cut into appropriate shapes for each analysis. Thermal stability was studied by thermogravimetric analysis (TGA) and differential scanning calorimetry (DSC). Mechanical properties were evaluated by tensile testing. Morphology of cone calorimetry (CC) residues was examined using SEM. Flammability properties, studied using CC, revealed a 70% reduction in the peak heat release rate (pHRR) and a 48% reduction in the total heat release (THR) compared to the neat LDPE/EVA blend. These results indicate that StVTz and APP act synergistically to improve the flame-retardant properties of LDPE/EVA. Full article

A novel Ag(I) coordination polymer, [Ag₂(bipy)(btca)]_n, (SCP 1) was synthesized using 4,4′-bipyridyl (bipy) and 1,2,4,5-benzene-tetracarboxylic acid (H₄BTC). Characterization by FT-IR, ¹H/¹³C NMR, and single-crystal X-ray diffraction confirmed its 3D network structure. The structure of SCP 1 consists of two chains arranged in …ABAB… fashion. Chain A is one-dimensional, containing [Ag(4,4′-bipy)]_n chain, while chain B is free, containing uncoordinated 1,2,4,5-benzene tetracarboxylate and water molecules. The stacking and argentophilic interactions extend the chain A of [Ag(4,4′-bipy)]_n into a two-dimensional layer. In contrast, chain B of uncoordinated 1,2,4,5-benzene tetracarboxylate and water molecules form a 1-D chain through extensive hydrogen bonds between water molecules and BTC ions and between water molecules themselves. Chains A and B are connected through extensive hydrogen bonds, generating a three-dimensional network structure. This Silver I supramolecular coordination polymer (SCP 1) demonstrated high catalytic activity as a recyclable heterogeneous catalyst for the synthesis of 5-substituted 1H-tetrazoles via [3+2] cycloaddition of NaN₃ and terminal nitriles under solvent-free conditions in a Q-tube pressure reactor (yields: 94–99%). A mechanistic proposal involving cooperative Lewis acidic Ag(I) sites and Brønsted acidic -COOH groups facilitates the cycloaddition and protonation steps. SCP 1 catalyst exhibits reusability up to 4 cycles without significant loss of activity. The structural stability of the SCP 1 catalyst was assessed based on PXRD and FTIR analyses of the catalyst after usage, confirming its integrity during the recycling process. Full article

Five-membered nitrogen heterocycles exhibit a diverse range of applications across various fields, including medicine, agrochemicals, and materials science. Worldwide industries have exploited hazardous organic solvents and catalysts to afford key bioactive heterocycles, which in turn have a devastating impact on the aqueous environment. The tremendous rise in environmental contamination has shifted the focus of the scientific community towards sustainable alternatives. In line with this, ionic liquids have received the attention of investigators and are widely preferred in organic transformations as catalysts, solvents, ligands, and co-catalysts. Ionic liquids exhibit superior physicochemical properties, such as non-volatility, excellent conductivity, low vapour pressure, non-flammability, and electrochemical and thermal stability, thereby emerging as a clean and efficient alternative to the hazardous volatile organic solvents. The ionic-liquid-assisted synthetic approach has become a popular, greener method owing to high efficiency and product yield with notable purity. Thus, the present article aimed at highlighting catalytic applications of ionic liquids in the synthesis of aromatic five-membered nitrogen heterocycles such as pyrrole, pyrazole, imidazole, 1,2,3-triazole, 1,2,4-triazole, and tetrazole. This article will provide an insight into ionic liquids for their further exploration in organic transformations and related applications. Full article

The synthesis of heterocyclic compounds has gained significant attention in organic chemistry due to their diverse pharmacological properties. However, traditional synthetic approaches often involve hazardous chemicals, high energy consumption, and tedious workup procedures, leading to environmental concerns and low yields. In response, green chemistry strategies have emerged, emphasizing safer and more sustainable alternatives. Among these, magnetic nanoparticle (MNP)-based catalysts have shown remarkable promise in facilitating one-pot multicomponent reactions (MCRs), offering enhanced catalytic efficiency, ease of recovery, and reusability. This article provides a comprehensive overview of multicomponent reactions (MCRs) for the construction of a wide range of heterocyclic scaffolds—including chromenes, pyrazoles, phenazines, triazoles, tetrazoles, xanthenes, furans, indoles, imidazoles, pyridines, pyrimidines, oxazoles, and acridine derivatives—catalyzed by magnetic nanoparticles under sustainable and environmentally benign conditions. This review highlights recent advances (2018–2024) in the development and application of modified magnetic nanoparticles for green multicomponent synthesis. Emphasis is placed on their structural features, catalytic roles, and benefits in eco-friendly organic transformations. Full article

The development of molecules that interact with G-quadruplex (G4) sequences requires effective evaluation methods. Several techniques are currently available, including nuclear magnetic resonance (NMR) spectroscopy and X-ray crystallography, surface plasmon resonance (SPR), isothermal titration calorimetry (ITC) and mass spectrometry (MS), fluorescence using FRET-melting, G4-fluorescent intercalator displacement assay (G4-FID) and affinity chromatography. Among these, CD spectroscopy is gaining prominence due to its lower material requirements, faster experimentation and quicker data processing. However, conventional CD methods have limitations, such as higher sample volume required and the inability to handle high-throughput analysis efficiently. The use of synchrotron radiation in high-throughput analysis methods (HT-SRCD) has further advanced the investigation of small-molecule interactions with DNA G4 structures in the presence of various monovalent cations. HT-SRCD offers the capability to analyze multiple samples simultaneously, overcoming the limitations of conventional CD methods. To validate this approach, three biologically relevant G4 sequences—HTelo1, G3T3 and T95-2T—were investigated. Their interactions with a library of small tetrazole-based molecules, synthesized via a four-component Ugi reaction, and with a peptide sequence deriving from RHAU helicases (Rhau25), were evaluated. The results demonstrate that this method not only effectively discriminates between different ligands but also provides valuable insights into the selectivity and the modes of interaction of these ligands with the G4 sequences. Full article

The objective of this work was the synthesis and characterization of novel, insensitive high explosives. 1-hydroxy-5-methyltetrazole served as both a scaffold and anion for preparing various nitrogen-rich energetic salts. The compounds were characterized using ¹H and ¹³C NMR spectroscopy, high-resolution mass spectrometry, elemental analysis, low-temperature single-crystal X-ray diffraction, and IR spectroscopy. Thermal stability was investigated via differential thermal analysis (DTA). Sensitivities towards mechanical stimuli were measured using a BAM drop hammer for impact sensitivity and a BAM friction apparatus for friction sensitivity, employing one of six testing procedures. Energetic performance parameters were calculated using the EXPLO5 code, incorporating room-temperature X-ray densities and solid-state heats of formation obtained via CBS-4M calculations using the Gaussian 16 program. Full article

Chitosan is a natural, biocompatible, biodegradable, and non-toxic polymer that has consistently garnered the attention of researchers in the development of new materials across various applications. Typically, to impart the desired properties to chitosan, chemical modification is necessary. Therefore, the development of simple and convenient methods for the chemical modification of chitosan is crucial in polymer chemistry. In this work, the approaches of Click chemistry and the necessary electrochemistry, which have recently illuminated the chemistry of chitosan, were combined to achieve a straightforward and efficient synthesis of new tetrazole chitosan derivatives. This was accomplished through electrochemical coupling. The proposed synthesis method is simple, convenient, and fast, hence allowing for the easy production of low- (10%), moderate- (30%), and highly substituted (65%) tetrazole chitosan derivatives. The highly substituted chitosan derivatives exhibit high activity as catalysts for the aldol reaction, achieving almost 100% conversion in just 15 min. Notably, these derivatives enable the aldol reaction to be catalyzed in water, aligning with one of the key principles of green chemistry. Furthermore, the new tetrazole chitosan derivatives demonstrate significant in vivo antibacterial effects in the treatment of peritonitis in rats. The primary mechanism of their antibacterial action is the disruption of the bacterial cell membrane integrity. Full article