Tetrazole Derivatives Research Articles

Investigating the Impact of Packing and Environmental Factors on the Luminescence of Pt(N^N^N) Chromophores.

Four Pt(II)(N^N^N) compounds featuring DMSO coordination at the fourth position were synthesized. Ligands varied in terms of pyridyl central ring (hydrogen/chlorine substituent) and lateral rings (triazoles with CF3 substitution or tetrazoles). Coordination to pyridine yielded tetra-nitrogen coordinated Pt(II) complexes or Pt-functionalized polymers using commercial 4-pyridyl polyvinyl (PV) or dimethylaminopyridine. Luminescence behaviors exhibited remarkable environmental dependence. While some of the molecular compounds (tetrazole derivatives) in solid state displayed quenched luminescence, all the polymers exhibited 3MMLCT emission around 600 nm. Conversely, monomer emission was evident on poly(methyl methacrylate) or polystyrene matrices. DFT calculations were used to analyze the aggregation of the complexes both at the molecular level and coordinated to the PV polymer and their influence on the HOMO-LUMO gaps.

Inhibiting general and pitting corrosion of Ni in dilute sulfuric acid solutions with some tetrazole derivatives

5-(Benzylthio)− 1H-tetrazole (BST), ethyl-1H-tetrazole-5-acetate (ETA), and 5-(ethylthio)− 1H-tetrazole (EST) were utilized to inhibit the pitting and general corrosion of nickel in dilute sulfuric acid solutions. The galvanostatic anodic polarization under a constant current and mass loss measurement complemented by a scanning electron microscope is utilized. The tetrazole inhibitors retard the pitting corrosion by shifting the pitting potential, Ep into the more noble direction while lowering the amount of electricity, Qinh, needed to attain Ep. The protection efficiency, η, increased with increasing the amount of tetrazole in the solution to follow the order EST < ETA < BST. The protection influence of such inhibitors is accompanied by the blocking of the investigated metal surface by their molecules through an adsorption process that follows Langmuir's model. The computed -∆G⸰ads values are 37.17, 36.82, and 36.57 kJ/mol for BST, ETA, and ETA, successively, at 298 K. Such values are harmonious with a mixed chemo-, physisorption mechanism. A coordinate link is supposed to originate between the tetrazole compound and the investigated nickel surface.

Interaction mechanism studies of 1H-tetrazole derivatives and nitrocellulose. Part 1: introduction of amino groups on C and N atoms

The interaction analysis: the addition of aminotetrazole (5-ATZ and DATZ) mainly affected the autocatalytic reaction at the initial stage of the pyrolysis process of NC. The imino form of 5-ATZ or DATZ played an important role in this process.

A multidentate copper complex on magnetic biochar nanoparticles as a practical and recoverable nanocatalyst for the selective synthesis of tetrazole derivatives

Waste recycling, novel and easy methods of recycling catalysts, use of green solvents, use of selective catalysts and preventing the production of by-products are the most important principles of green chemistry and modern technology.

Design, synthesis, in vitro and in silico evaluation of indole-based tetrazole derivatives as putative anti-breast cancer agents.

A series of new indole-tetrazole derivatives were designed and synthesized to develop potential anti-breast cancer agents. The compounds exhibited in vitro anti-proliferative activity against ER-α positive T-47D (IC50 = 3.82-24.43 μM), MCF-7 (IC50 = 3.08-22.65 μM), and ER-α negative MDA-MB-231 (IC50 = 7.69-19.4 μM) human breast cancer cell lines. Compounds 5d and 5f displayed significant anti-proliferative activity compared to bazedoxifene (IC50 = 14.23 ± 0.68 μM), with IC50 values of 10.00 ± 0.59 and 3.83 ± 0.74 μM, respectively, against the ER-α dominant T-47D cell line. Also, both compounds showed non-significant cytotoxicity against normal cells HEK-293. Further, the ER-α binding affinity of 5d and 5f was assessed through a fluorescence polarization-based competitive binding assay, where 5d and 5f have shown significant binding with IC50 = 5.826 and 110.6 nM, respectively, as compared to the standard drug bazedoxifene (IC50 = 339.2 nM). Western blot analysis confirmed that compound 5d reduced ER-α protein expression in T-47D cells, hindering its transactivation and signalling pathways. Additionally, a molecular docking study suggests that compounds 5d and 5f bind in such a fashion that induces conformational changes in the protein, culminating in their antagonistic effect. Pharmacokinetic profiles showed that the compounds possessed drug-like properties. Furthermore, molecular dynamics simulation studies establish the dynamic stability and conformational behaviour of the ER-α protein and ligand complex of both compounds. Additionally, 5d and 5f ensure biological feasibility as per their DFT analysis through HOMO-LUMO energy gap analysis. In conclusion, compounds 5d and 5f, exhibiting significant ER-α antagonistic activity, can act as potential lead compounds for anti-breast cancer therapies.

Green Methodologies for Tetrazole Synthesis from Different Starting Materials: A Recent Update

Abstract: Tetrazole is a most versatile pharmacophore of which more than twenty FDAapproved drugs have been marketed globally for the management of various diseases. In spite of many remarkable and consistent efforts having been made by the chemists towards the development of greener and sustainable strategies for the synthesis of tetrazole derivatives, this approach still needs more attention. The present review focuses on the green synthetic approach for the preparation of tetrazole derivatives from different starting materials such as nitrile, isonitrile, carbonyl, amine, amide, oxime and terminal alkyne functions. The mechanism of tetrazole synthesis from different substrates is discussed. In addition to this, a four component Ugi-azide reaction to the tetrazole synthesis is also described. Of note, the present articles exploited several water-mediated and solvent-free methodologies for tetrazole synthesis. The important key features of tetrazole synthesis were pinpointing in each synthetic scheme which provides excellent guide to those searching for selective procedure to achieve the desired transformation. This review seeks to present a timely account (2011-2023) on the splendid array of ecofriendly procedures of synthesis known today for the preparation of tetrazole derivatives from different starting materials. The rational of this review is to enlighten recent advancements in the synthesis of tetrazole derivatives from different substrates.

Modification of gradient HPLC method for determination of small molecules' affinity to human serum albumin under column safety conditions: Robustness and chemometrics study

In the early stages of drug discovery, beyond the biological activity screening, determining the physicochemical properties that affect the distribution of molecules in the human body is an essential step. Plasma protein binding (PPB) is one of the most important investigated endpoints. Nevertheless, the methodology for measuring %PPB is significantly less popular and standardized than other physicochemical properties, like lipophilicity. Here, we proposed how to modify protocols presented by Valko into column safety conditions and evaluated their robustness using fractional factorial design. For robustness testing, four factors were selected: column temperature, mobile phase flow rate, maximum isopropanol concentration in the mobile phase, and buffer pH. Elaborate methods have been applied for the analysis of HSA affinity for three groups of antibiotic-oriented substances that vary in chemical structure: fluoroquinolones, sulfonamides, and tetrazole derivatives. Furthermore, based on the reversed-phase chromatography the workflow of pilot studies was proposed to select molecules that have high affinity to HSA and can not be eluted from the HSA column using the concentration of organic modifier recommended by the column manufacturer.

Homoselective Synthesis of tetrazoles and chemoselective oxidation of sulfides using Ni(II)-Schiff base complex stabilized on 3-dimensional mesoporous KIT-6 surface as a recyclable nanocatalyst

Mesoporous silica with thick expanded walls, open porosity, and excellent thermal stability is a relatively new structure known as KIT-6. In this study, KIT-6 mesoporous was synthesized by using pluronic surfactant P123 as a modulator in an acidic environment. The synthesized KIT-6 was then modified by 3-chloropropyltrimethoxysilane (3-CPTMS) and finally, the nickel metal complex was fixed on the modified mesoporous KIT-6. IR, BET, XRD, EDS, SEM, AAS, and TGA methods were employed to examine the as-prepared catalyst. The proposed catalyst was then used for selective sulfides oxidation and preparation of tetrazole derivatives. The synthesized catalyst was found to be efficient and practical as it produced organic compounds in proper TOF and TON amounts, demonstrating the catalyst's practicality and efficiency.

Tetrazoles and Related Heterocycles as Promising Synthetic Antidiabetic Agents.

Tetrazole heterocycle is a promising scaffold in drug design, and it is incorporated into active pharmaceutical ingredients of medications of various actions: hypotensives, diuretics, antihistamines, antibiotics, analgesics, and others. This heterocyclic system is metabolically stable and easily participates in various intermolecular interactions with different biological targets through hydrogen bonding, conjugation, or van der Waals forces. In the present review, a systematic analysis of the activity of tetrazole derivatives against type 2 diabetes mellitus (T2DM) has been performed. As it was shown, the tetrazolyl moiety is a key fragment of many antidiabetic agents with different activities, including the following: peroxisome proliferator-activated receptors (PPARs) agonists, protein tyrosine phosphatase 1B (PTP1B) inhibitors, aldose reductase (AR) inhibitors, dipeptidyl peptidase-4 (DPP-4) inhibitors and glucagon-like peptide 1 (GLP-1) agonists, G protein-coupled receptor (GPCRs) agonists, glycogen phosphorylases (GP) Inhibitors, α-glycosidase (AG) Inhibitors, sodium glucose co-transporter (SGLT) inhibitors, fructose-1,6-bisphosphatase (FBPase) inhibitors, IkB kinase ε (IKKε) and TANK binding kinase 1 (TBK1) inhibitors, and 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1). In many cases, the tetrazole-containing leader compounds markedly exceed the activity of medications already known and used in T2DM therapy, and some of them are undergoing clinical trials. In addition, tetrazole derivatives are very often used to act on diabetes-related targets or to treat post-diabetic disorders.

Synthesis, antimicrobial and cytotoxic activities of tetrazole N-Mannich base derivatives: Investigation of DFT calculation, molecular docking, and Swiss ADME studies

Tetrazole derivatives are a prime class of heterocyclic compounds that are important for the design of drug molecules. In this study, the cytotoxicity and antimicrobial activity of a novel class of tetrazole N-Mannich base derivatives were investigated. The synthesised compounds were evaluated by FTIR, NMR spectroscopy, mass spectrometry, and elemental analysis. All synthesised compounds were investigated for antimicrobial activity; in particular, compound 2d was found to be more effective against S. aureus than cefazolin. Compound 2e was more effective than clotrimazole against Cryptococcus neoformans. All the synthesised compounds were investigated against cancer cell lines (HepG2, MCF-7, and HeLa); in particular, compound 2e was more active against the HeLa cancer cell line than doxorubicin. Synthesised compounds were studied for molecular docking interactions between proteins and synthesised molecules using the Auto Dock Vina 1.1.2 programme. According to molecular docking studies, 2d has a greater docking score (-6.4 kcal/mol) compared with cefazolin (-5.8 kcal/mol) for the 1BQB protein and 2e was equal docking score compared with clotrimazole (-2.3 kcal/mol) for the 3SFX protein. Density functional theory (DFT) was used to perform calculations for highly and low-active compounds in order to estimate the energy gaps 2e and 2d (∆E = 0.1, and 0.21 eV). Additionally, we discuss the role of the Swiss ADME tool in determining the physicochemical properties of all synthesised compounds. According to the results, the newly synthesised tetrazole derivatives may have medicinal importance and could be used as antibacterial agents.

Design, synthesis, characterization and application of magnetic biochar as a reusable nano catalyst for the synthesis of tetrazole derivatives

Design, synthesis, characterization and application of magnetic biochar as a reusable nano catalyst for the synthesis of tetrazole derivatives

Development of Dual Inhibitors of Soluble Epoxide Hydrolase/Fatty Acid Amide Hydrolase with Tetrazole Core.

The attractive biological actions of the eicosatrienoic acids (EETs) and endocannabinoids (eCBs) are terminated by means of enzymatic hydrolysis via soluble epoxide hydrolase (sEH) and fatty acid amide hydrolase (FAAH) enzymes. Simultaneous inhibition of both enzymes is considered a novel approach in the treatment of inflammatory and neuropathic pain. In this study, a novel series of tetrazole derivatives as dual sEH/FAAH inhibitors were designed, synthesized, and biologically evaluated. Compounds 6c, 7d, and 8a, the most potent inhibitors against FAAH and sEH enzymes with acceptable IC50 values, significantly decreased carrageenan- induced paw edema 5h after carrageenan injection compared to the control group compound. In addition, compound 7d exhibited a significant reduction in pain scores compared to the control group. Docking studies showed that the presented dual inhibitors could bind to the essential residues in the catalytic sites of both enzymes. In silico prediction of several pharmacokinetic properties suggests that these dual inhibitors could potentially be orally active agents. These structures will be a valuable scaffold to develop soluble epoxide hydrolase inhibitors with dual potency towards fatty acid amide hydrolase.

Molecular structure impacts of tetrazole derivatives on their diffusion and adsorption behaviors for microvia copper void-free filling

Optimizing a high-quality leveler has become the core task in developing the microvia copper filling technology. In this work, two nitrogen-containing heterocyclic compounds, iodonitrotetrazolium chloride (INT) and thiazolyl blue tetrazolium bromide (MTT) with a similar tetrazolyl group are selected as the levelers to investigated the molecular structure impacts on their microvia copper filling performance. Both INT and MTT inhibit the electroreduction of copper ions. The inhibiting effect of INT is greatly enhanced by convection while MTT is independent of convection, indicating a bottom-up filling performance of INT and a conformal filling performance of MTT. The microvias are supper-filled and poor-filled in electrolytes containing INT and MTT, respectively, as predicted by electrochemical analysis. Molecular dynamic simulation demonstrates that INT adsorbs in a flat orientation with its iodine and nitro group's two oxygen atoms interacting on the Cu(111) plane surface. MTT adsorbs on Cu(111) surface via positively charged tetrazole ring and its adsorption ability is much stronger than that of INT. The weak adsorption ability of INT on copper surface and the slow mass transfer rate result in its convection-dependent adsorption behavior and the excellent microvia copper filling performance.

Synthesis and in Silico Studies of Some New 1,2,3-Triazolyltetrazole Bearing Indazole Derivatives as Potent Antimicrobial Agents.

1,2,3-Triazole and tetrazole derivatives bearing pyrrolidines are found to exhibit notable biological activity and have become useful scaffolds in medicinal chemistry for application in lead discovery and optimization. Novel indazole bearing 1,2,3-triazolyltetrazoles were designed as potential antimicrobial candidates. The structure of duel heterocyclics was validated by a spectroscopic technique of infrared (IR), nuclear magnetic resonance (1 H and 13 C NMR), and mass spectral data. Compounds 4b, 4c, 4d, and 4h were found to have a stronger antibacterial effect against Gram-positive (S. aureus, B. subtilis, M. Luteus) and Gram-negative (E. coli, P. aeruginosa) microorganisms with MICs ranging from 5±0.03-18±0.02 μM, respectively. Moreover, scaffolds 4a, 4h showed potent antifungal activity against A. flavus, M. gypsuem strains with MIC values of 10±0.02, 11±0.01 μM, which are similar activity that of the standard Itraconazole (MIC=8±0.02, 10±0.01 μM). The binding mode for compound 4 inside the catalytic pocket of S. aureus complexed with nicotinamide adenine dinucleotide phosphate and trimethoprim and produced a network of hydrophobic and hydrophilic interactions (3FRE). From in silico results, 4b demonstrated highly stable hydrogen binding amino acids Leu62(X) [N18…O, 2.47 Å], Arg44(X) [N17…N, 3.11 Å], Thr96(X) [N10…OG1, 3.05 Å], Gly94(X) [F7…N, 2.82 Å], and Gly43(X) [F7…N, 2.90 Å], which are plays a crucial role in ensuring efficient binding of the ligand in a crystal structure of antibacterial receptor. Furthermore, the physicochemical and ADME filtration molecular properties, estimation of toxicity, and bioactivity scores of these novel scaffolds were evaluated by using SwissADME and ADMETlab2.0 online protocols. Thus, the significant antimicrobial activity of indazole linked to duel heterocyclic compounds can be used for development of new antimicrobial agents with further modifications.

Energetic metal-organic framework based on multinuclear clusters of Cu(II) and Fe(III) and its catalytic action on thermal decomposition of solid propellant components (RDX, HMX, CL-20 and AP)

Using nitrogen-rich tetrazole derivatives with multifunctional groups and ligand sites in metal–organic frameworks (MOFs) is a strategy to enhance their energy levels and broaden their applications. In the present study, a Cu(II) and Fe(III) heteronuclear {[CuFe3O(tza)6(H2O)3]·(NO3)2·OH}n (CuFe-MOF) based on the high-energy ligand tetrazole-1-acetic acid (Htza) was synthesized and its structures and properties were evaluated. The effects of CuFe-MOF as a catalyst on the thermal decomposition performance of the solid propellant components (RDX, HMX, CL-20 and AP) were investigated. The results demonstrated that the successfully prepared compound, an infinite 3D meshwork structure composed of [Fe3O(tza)6]+ and Cu2+, is in the ortho-hexagonal crystal system, P63/m space group. CuFe-MOF exhibited good thermal stability (Tdec = 238.9 °C) and insensitivity to impact (IS > 40 J) and friction (FS > 360 J). The addition of 5 % CuFe-MOF significantly reduces the decomposition peak temperature (1.9 °C, 5.8 °C, 5.7 °C and 71.4 °C) and apparent activation energy (38.5 kJ·mol−1, 38.3 kJ·mol−1, 63.9 kJ·mol−1, and 27.0 kJ·mol−1) of the RDX, HMX, CL-20, and AP compared to the raw materials while notably enhancing the heat release (509.8 J·g−1, 613.1 J·g−1, 578.4 J·g−1 and 584.3 J·g−1). Furthermore, good compatibility with RDX, HMX, CL-20, and AP was demonstrated using VST method. This research indicates the potential of {[CuFe3O(tza)6(H2O)3]·(NO3)2·OH}n as a promising alternative to the existing inert catalysts in propellants containing RDX, HMX, CL-20, and AP components, serving as an energetic combustion catalyst.

Tetrazole derivatives as potent immunomodulatory agents in tumor microenvironment

Twenty-seven compounds bearing a tetrazole ring as a central unit have been designed, synthetized and biologically evaluated. Studies have been performed in order to compare the effect of tetrazole derivatives bearing amine electron-donor or nitro electron-acceptor groups. The antiproliferative activity has been determined in monoculture studies on tumor cell lines HT-29, A-549, MCF-7 and on non-tumor cell line HEK-293 as well as in co-culture studies (HT-29/THP-1). All the compounds have been studied as PD-L1 (Programmed Death Ligand 1), VEGFR-2 (Vascular Endothelial Growth Factor 2), CD-47 (Cluster of Differentiation 47) and c-Myc inhibitors. The effect on TNF-α secretion has also been determined. Bromoderivatives 23, 24 and chloroderivatives 26, 27 have demonstrated an apoptotic effect on HT-29 cancer cells. Compounds bearing an amine group have shown very promising effects as TME immunomodulatory agents.

One-pot synthesis, computational chemical study, molecular docking, biological study, and in silico prediction ADME/pharmacokinetics properties of 5-substituted 1H-tetrazole derivatives

An efficient synthesis of 5-substituted 1H-tetrazoles was successfully achieved through one-pot multi-component condensation reactions of some aromatic aldehydes or indolin-2,3-dione with malononitrile and sodium azide using diverse reaction conditions to obtain considerable product yields. Furthermore, it has been achieved for the first time to construct desired products under neat condition. Molecular docking studies with CSNK2A1 receptor disclosed the lowest binding energy displayed by the dimethoxyphenyl derivative 4c with − 6.8687 kcal/mol. The synthesized tetrazoles were screened for their in-vitro cytotoxic activity against epidermoid cancer cell line (A431) and colon cancer line (HCT116) with respect to normal skin fibroblast cell line (BJ-1) using MTT assay, and antimicrobial activity against the bacteria: K. pneumonia, S. aureus, and the fungi: Candida albicans, as well as their antioxidant activity using 2,2-diphenyl-1-picrylhydrazyl assay. In addition, the toxicity of tetrazole derivative was assessed by determination of their approximate lethal dose fifty (LD50), calculated via an oral administration to rats, through measurement of ALT and bilirubin levels in serum. The antitumor results can suggest that the potent tetrazole derivative namely, 3-(3,4-dimethoxyphenyl)-2-(1H-tetrazol-5-yl)acrylonitrile (4c) could be a potential drug against epidermoid carcinoma. The antioxidant results indicated to tetrazoles exhibited great antioxidant properties even at very low doses. A molecular dynamics simulation was performed for the synthesized compounds (ligands) to investigate their tendency for binding with the active sites of protein.

Synthesis, Characterization of New Phenylene Bis Tetrazole and Bis Benzoxazepinedione Derivatives from some Bis Imines with its Biological Activity Assessment.

Synthesis, Characterization of New Phenylene Bis Tetrazole and Bis Benzoxazepinedione Derivatives from some Bis Imines with its Biological Activity Assessment.

Experimental, computational investigations and biological evaluation on 1-(3-acetamidophenyl)-5-mercaptotetrazole-cytotoxicity MTT assay

The current research is Experimental, Computational investigations and biological evaluation on 1-(3-Acetamidophenyl)-5-mercaptotetrazole which is a tetrazole derivative. Tetrazole moiety has wide spectrum of pharmaceutical applications. Density Functional Theory is employed for theoretical analysis and optimized structure, molecular geometry was obtained. Vibrational assignments and PED values were calculated. Experimentally and theoretically FT-IR, FT-Raman studies were carried out. Topology studies ELF, LOL and RDG were done on the title compound. UV analysis was done and peaks were obtained by both experimentally and theoretically with different solvents. HOMO LUMO energies and energy gap were also identified. MEP, NLO and Natural Bonding Orbital calculations were performed on title compound. Drug likeness properties and Ramachandran plot were identified. Finally, Molecular docking against anti-convulsant targets were performed using autodock tools and visualized with Discovery studio software. Theoretical results are compared with experimental results, which is in good agreement. Cytotoxicity assay studies were done on title compound. Results reveals that this compound is nontoxic and can be used as a anti – convulsant.

Fe3O4@SiO2@BHA-Cu(II) as a new, effective, and magnetically recoverable catalyst for the synthesis of polyhydroquinoline and tetrazole derivatives

Fe3O4@SiO2@BHA-Cu(II) as a new, effective, and magnetically recoverable catalyst for the synthesis of polyhydroquinoline and tetrazole derivatives