Search

A new library of tetrazole rings with oxazole-pyrimidine derivatives (9a–j) has been developed and synthesized. All of the compounds were characterized using spectral data. These were then tested for in vitro anticancer activity against four human cancer cell lines: prostate cancer (PC3 & DU-145), lung cancer (A549), and breast cancer (MCF-7) using an MTT assay. Etoposide was chosen as the positive control. Most of the compounds demonstrated moderate to good activity. These compounds (9a, 9b, 9d, 9g, and 9h) demonstrated the most powerful action. Particularly, one chemical 9h had exceptional antitumor efficacy. [ABSTRACT FROM AUTHOR]

Cellulose is the most common renewable polysaccharide on the planet and one of the most important sources of green support to generate catalysts. According to that, the fluffy cotton-like seed of the black poplar tree (Populus nigra subsp. betulifolia) was first used as a source of natural cellulose to construct the green, efficient, and recyclable catalyst for the synthesis of cyclic carbonate from carbon dioxide (CO2). Black poplar cotton (BPC) was efficiently oxidized to dialdehyde cellulose (DAC) using periodate and participated in the azido-Ugi four-component reaction (AU-4CRs) of sulfonamide, isocyanide, and sodium azide to produce tetrazole immobilized on cellulose (DAC-AU) as a ligand. Afterward, the heterogeneous biocatalyst (Cu(II)@DAC-AU) was prepared, and the catalytic activity of the biocatalyst was investigated in the cycloaddition reaction of epoxides and CO2. This study has proven to have the most optimal catalytic activity, including excellent performance up to 99% after 4 h under CO2 pressure of 1 bar. The hydroxy and tetrazole functional groups on the surface of cellulose can absorb CO2 effectively and improve its catalytic activity. This work highlights the applications of the biocatalyst in a cycloaddition reaction and provides an efficient remedy for the industrial conversion of CO2. [ABSTRACT FROM AUTHOR]

NH-Heterocycles were studied as nucleophiles in Bargellini reaction. It was shown that 5-substituted tetrazoles, 1-substituted tetrazol-5-ones, and 1,2,3-triazoles easily react with chloroform and acetone or cyclopentanone in the presence of NaOH. The effect of the reactant's nature, their ratio and temperature on the reaction outcome was studied. The presented procedure provides the corresponding derivatives of hindered carboxylic acids in good yields. In the case of 5-substituted tetrazoles the reaction led exclusively to N2 isomer. [ABSTRACT FROM AUTHOR]

Inexpensive and recyclable catalysts, waste regeneration, that utilize safe and available solvents are important factors in laboratory and industrial applications. On the other hand, biochar nanoparticles are new precursors for the solid phase of carbon materials with novel characteristics, which exists synthetically or naturally. Therefore in this work, biochar nanoparticles were prepared from the pyrolysis of biomass resulting from chicken manure. Therefore, it is a suitable method for biomass waste recycling. Then, the surface of biochar nanoparticles was modified by (3-aminoopropyl)trimethoxysilane in n-hexane for 24 h at 60 °C, which the modified biochar nanoparticles were named nPr-NH2@biochar. Next, the modified biochar nanoparticles were functionalized by di(pyridin-2-yl)methanone (DPMI) in ethanol at 80 °C for 24 h, and the functionalized biochar nanoparticles were named as DPMI@biochar. Finally, a new copper Schiff-base complex of di(pyridin-2-yl)methanimine (DPMI) was immobilized on the surface of functionalized biochar nanoparticles (Cu-DPMI@biochar). This biochar-based catalyst nanostructure (Cu-DPMI@biochar) was used as a practical and reusable catalyst in the homoselective synthesis of 5-substituted-1H-tetrazole compounds by [3 + 2] cycloaddition reaction of sodium azide and nitrile derivatives. This catalyst was characterized by scanning electron microscopy (SEM), wavelength-dispersive X-ray spectroscopy (WDX), energy-dispersive X-ray spectroscopy (EDS), thermogravimetric analysis (TGA), X-ray powder diffraction (XRD), N2 adsorption/desorption isotherms, Fourier transform infrared spectroscopy (FTIR), and atomic absorption spectroscopy (AAS) techniques. Cu-DPMI@biochar can be recovered and reused several times. [ABSTRACT FROM AUTHOR]

An efficient access to the novel 5-(aryl)amino-1,2,3-triazole-containing 2,1,3-benzothiadiazole derivatives has been developed. The method is based on 1,3-dipolar azide–nitrile cycloaddition followed by Buchwald–Hartwig cross-coupling to afford the corresponding N-aryl and N,N-diaryl substituted 5-amino-1,2,3-triazolyl 2,1,3-benzothiadiazoles under NHC-Pd catalysis. The one-pot diarylative Pd-catalyzed heterocyclization opens the straightforward route to triazole-linked carbazole-benzothiadiazole D-A systems. The optical and electrochemical properties of the compound obtained were investigated to estimate their potential application as emissive layers in OLED devises. The quantum yield of photoluminescence (PLQY) of the synthesized D-A derivatives depends to a large extent on electron-donating strengths of donor (D) component, reaching in some cases the values closed to 100%. Based on the most photoactive derivative and wide bandgap host material mCP, a light-emitting layer of OLED was made. The device showed a maximum brightness of 8000 cd/m2 at an applied voltage of 18 V. The maximum current efficiency of the device reaches a value of 3.29 cd/A. [ABSTRACT FROM AUTHOR]

This current investigation represents the new series of fused thieno-pyrimidine with synthesized tetrazole analogs (6a–j). Intermediates thieno-[2,3-d]- pyrimidine were prepared by utilizing the Gewald method, and tetrazole (5a–j) was synthesized by [3 + 2] cycloaddition of azide and appropriate nitrile. All the prepared novel molecules were characterized and confirmed by ¹HNMR, 13CNMR, LC-MS, and FT-IR spectral analysis. [ABSTRACT FROM AUTHOR]

To obtain novel high-energy density compounds with superior detonation properties and sensitivity to those of RDX, a series of furazan/tetrazole/tetrazine-tetrazole-N = N-tetrazole-furazan/tetrazole/tetrazine and furazan/tetrazole/tetrazine-tetrazole-NHNH-tetrazole-furazan/tetrazole/tetrazine-based energetic materials were designed. Their structures were optimised by Gaussian software with density functional theory at B3LYP/6-311G (d,p) level. Based on the optimised structures, their frontier orbital energies, heats of formation and detonation properties were calculated. The results indicate that the compound with tetrazole-tetrazole-N = N-tetrazole-tetrazole parent structure and -N3 energetic group has the highest value of heat of formation while the compound with tetrazine-tetrazole-NHNH-tetrazole-tetrazine parent structure and -C(NO2)3 energetic group possess the highest values of detonation velocity and detonation pressure. Most of the designed compounds have higher values of h50 than those of RDX (28 cm) and HMX (32 cm), and series E had higher average values of impact sensitivity. Finally, taking detonation properties and impact sensitivity into consideration, six compounds (A2, A8, C8, D2, F7 and F8) were selected as potential candidate materials for high-energy density materials, and their electronic and physicochemical properties were investigated. [ABSTRACT FROM AUTHOR]

New derivatives of 2-methoxy-1-tetrazolylmethyldiazene 1-oxides bearing additional explosophoric groups were synthesized. The reactions of the appropriate aminotetrazoles with trinitromethane in the presence of paraformaldehyde gave trinitroethylamine derivatives and nitration of these aminotetrazoles with dinitrogen pentoxide led to nitramines. [ABSTRACT FROM AUTHOR]

Reactions between 1,2-di(tetrazol-2-yl)ethane (ebtz), 1,6-di(tetrazol-2-yl)hexane (hbtz) or 1,1′-di(tetrazol-1-yl)methane (1ditz) and Fe(BF4)2 in the presence of adiponitrile (ADN), glutaronitrile (GLN) or suberonitrile (SUN) resulted in the formation of coordination polymers [Fe(μ-ebtz)2(μ-ADN)](BF4)2 (1), [Fe(μ-hbtz)2(μ-ADN)](BF4)2 (2), [Fe(μ-1ditz)2(GLN)2](BF4)2·GLN (3) and [Fe(μ-1ditz)2(μ-SUN)](BF4)2·SUN (4). It was established that the application of dinitriles allows an increase in the dimensionality of the ebtz and hbtz based systems while maintaining the structure of the polymeric units characteristic of previously studied mononitrile based analogues. In 3 and 4, regardless of the type of dinitrile coligand, the motif of 2D polymeric layers constituted by 1ditz molecules remains preserved. However, the dimensionality of 1ditz based networks is governed by the coordination modes of dinitriles. 3, based on a shorter molecule of glutaronitrile, crystallizes as a two-dimensional (2D) coordination polymer. In this compound, dinitriles coordinate monodentately or play the role of guest molecules. The substitution of glutaronitrile with suberonitrile enables the bridging of neighboring polymeric layers, resulting in a 3D network. The intentional selection of bis(tetrazoles) and dinitriles as building blocks has led, as expected, to obtaining systems with the structure of the first coordination sphere consisting of four tetrazole rings and two axially coordinated nitrile molecules. It created the conditions required for the occurrence of thermally induced spin crossover. Magnetic measurements and single crystal X-ray diffraction studies were used for the characterization of the spin crossover properties of 1–4. [ABSTRACT FROM AUTHOR]

Background: Phosphodiesterase 3 (PDE-3) inhibition have been implicated in the neurobiologic underpinnings of migraine. Considering the clinical similarities between migraine and persistent post-traumatic headache (PPTH), we aimed to ascertain whether PDE-3 inhibition can elicit migraine-like headache in persons with PPTH. Methods: We tested cilostazol, which inhibits PDE-3, in a randomized, double-blind, placebo-controlled, two-way crossover study involving persons with PPTH attributed to mild traumatic brain injury. The randomized participants were allocated to receive oral administration of either 200-mg cilostazol or placebo (calcium tablet) on two separate experiment days. The primary end point was the incidence of migraine-like headache during a 12-hour observation window post-ingestion. The secondary endpoint was the area under the curve (AUC) for reported headache intensity scores during the same observation window. Results: Twenty-one persons underwent randomization and completed both experiment days. The mean participants' age was 41.4 years, and most (n = 17) were females. During the 12-hour observation window, 14 (67%) of 21 participants developed migraine-like headache post-cilostazol, in contrast to three (14%) participants after placebo (P =.003). The headache intensity scores were higher post-cilostazol than after placebo (P <.001). Conclusions: Our results provide novel evidence showing that PDE-3 inhibition can elicit migraine-like headache in persons with PPTH. Given that PDE-3 inhibition increases intracellular cAMP levels, our findings allude to the potential therapeutic value of targeting cAMP-dependent signaling pathways in the management of PPTH. Further investigations are imperative to substantiate these insights and delineate the importance of cAMP-dependent signaling pathways in the neurobiologic mechanisms underlying PPTH. ClinicalTrials.gov Identifier: NCT05595993. [ABSTRACT FROM AUTHOR]

New coordination compounds made of two novel tetrazole and C,N‐bipyrazole ligands, 2‐(3,5,5′‐trimethyl‐1′H‐[1,3′‐bipyrazol]‐1′‐yl)acetonitrile (L1), and 1′‐((1H‐tetrazol‐5‐yl)methyl)‐3,5,5′‐trimethyl‐1′H‐1,3′‐bipyrazole (HL2), were prepared and fully characterized by spectroscopic techniques. Their crystal structures were identified by single‐crystal X‐ray diffraction revealing mononuclear complexes: [Ni(L1)3](ClO4)2 (1), [Cd(L1)2Cl2] (2), [Cu(HL2)(L2)]ClO4 (3), [Cu(L2)2] (4) and a dinuclear complex [Co2(HL2)(L2)Cl3] (5) comprising CoII ions in octahedral and tetrahedral surrounding within the same unit. Noticeably, 3 and 4 show different architectural structures due to ligand deprotonation as well as the effect of the counter anion. All compounds demonstrated antimicrobial activity against Gram (+) bacteria Listeria innocua and Staphylococcus aureus, as well as Gram (−) bacteria such as Escherichia coli and Pseudomonas aeruginosa, and antifungal activity against pathogenic fungi Geotrichum candidum, Aspergillus niger, and Penicillium crustosum. Interestingly, a high inhibition activity of 97 % was reached for 5 with a low concentration of only 81.1 μmol/L against Fusarium oxysporum f. sp. Albedinis, which is commonly damaging palm trees crops. [ABSTRACT FROM AUTHOR]

This article discusses the development of a synthesis method for 3'-fluoro hexitol nucleic acids (FHNA) adenosine and guanosine phosphoramidites. The authors explain that antisense technology, which involves using oligonucleotides to downregulate gene expression, has shown promise in drug discovery. They describe the synthesis of FHNA pyrimidine nucleoside phosphoramidites and their properties, as well as the challenges faced in synthesizing FHNA purine nucleosides. The authors present two alternate routes for the synthesis of FHNA purine nucleosides and detail the steps involved in the synthesis process. They conclude that their synthetic method will facilitate the use of FHNA nucleic acids in genetic medicine and diagnostic applications. [Extracted from the article]

In this article, the mesoporous silica framework of KIT‐6 was synthesized and, then its surface was modified using 3‐aminopropyltrimethoxysilane (APTMS). The new KIT‐6@DABP@Cu nanocatalyst was then prepared by anchoring the copper complex on modified mesoporous KIT‐6. The nanocatalyst was identified using several techniques, including FT‐IR, WDX, AAS, SEM, TGA, XRD, EDS, and BET. The physical properties, such as size, shape, and morphology of the nanocatalyst were studied by SEM analysis. The elemental composition of KIT‐6@DABP@Cu nanocatalyst was described using wavelength dispersive X‐ray spectroscopy (WDX) and EDS. FT‐IR spectroscopy was used to characterize the functional groups in the structure of the nanoparticles. The stability of KIT‐6@DABP@Cu nanocatalyst was studied by TGA at high temperatures. Also, the surface area, total volume, and average diameter of pores of the nanocatalyst were determined using Brunauer–Emmett–Teller (BET) analysis. The KIT‐6@DABP@Cu catalyst was found to be a new, highly effective, and green catalyst for the synthesizing of 5‐substituted‐tetrazoles using nitriles and sodium azide (NaN3) catalyzed in polyethyleneglycol‐400 (PEG‐400) as a green solvent. This heterogeneous catalyst showed good recyclability for up to five consecutive cycles without notable loss of its catalytic efficiency. [ABSTRACT FROM AUTHOR]

In this contribution, new derivatives of bicyclic fused rings with a bridgehead nitrogen atom were synthesized from the imidazo[1,2-a]pyridine derivatives C1 by reacting two moles of 2-aminopyridine and 4-aminoacetophenone with iodine in a one-pot reaction. This compound (C1) was then condensed with 2- nitrobenzaldehyde and 2,4-dichlorobenzaldehyde to form new derivatives of Schiff bases (C2 and C3). These Schiff bases were then cyclized to synthesize thiazolidin4-one derivatives (C4 and C5), tetrazole derivatives (C6 and C7), and aza-β-lactam derivatives (C8 and C9) through the reactions with thioglycolic acid, sodium azide, and 1-naphthylisocyanate, respectively. FT-IR, 1H NMR, and 13C NMR spectroscopy were used to characterize these new compounds. In the second part of this work, the antioxidants of these compounds were measured, and results ranged from good to medium. [ABSTRACT FROM AUTHOR]

The synthesis of 1,4-disubstituted 1,2,3-triazoles through copper-catalyzed azide-alkyne cycloaddition (CuAAC) reaction has gained much attention due to its versatility and broad range of applications. In this study, we report two novel heterogeneous copper catalysts based on dehydroacetic acid chitosan Schiff base (DCSB) for the CuAAC reaction in water. The DCSB was synthesized through the condensation reaction of dehydroacetic acid and chitosan, and was subsequently used to support Cu(II) ions and CuO nanoparticles (CuO NPs). The prepared compounds were characterized using FT-IR, XRD, FE-SEM, EDX, BET, and TGA analyses. The performance of the catalysts was evaluated in a model reaction involving the 1,3-dipolar cycloaddition reaction of benzyl chloride, phenylacetylene, and sodium azide for the synthesis of 1,2,3-triazoles. After optimizing the reaction conditions, the scope of the reaction was extended to various substituted benzyl chlorides and alkyne molecules. Moreover, the recyclability of the catalysts was studied for up to four cycles. [ABSTRACT FROM AUTHOR]

BACKGROUND Arteriovenous fistula (AVF) is considered the gold standard for vascular access in hemodialysis. However, achieving the successful maturation of AVF remains a challenge. Cilostazol, a phosphodiesterase-3 inhibitor, has shown promise in enhancing AVF maturation. This study aimed to assess the clinical efficacy of cilostazol in promoting AVF maturation. METHODS This meta-analysis was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. A comprehensive systematic literature search was performed using PubMed, ScienceDirect, Cochrane Library, ProQuest, and Google Scholar to identify studies investigating the efficacy of cilostazol on the maturation of newly created AVF in patients with end-stage renal disease and published up to August 2023. The intervention group received perioperative cilostazol therapy, while the control group did not receive cilostazol. The outcomes were the maturation rate of AVF and AVF-related complications. Meta-analysis was conducted using Review Manager software version 5.3. RESULTS 5 studies involving 549 patients were included. The intervention group comprised 228 patients, while the control group comprised 321 patients. In the pooled analysis, patients in the intervention group had a significantly higher rate of AVF maturation (odds ratio [OR] = 2.18, 95% confidence interval [CI]: 1.29-3.68, p = 0.003, I² = 47%) and a lower rate of AVF-related complications (OR = 0.46, 95% CI: 0.28-0.77, p = 0.003, I² = 27%) compared to the control. CONCLUSIONS Cilostazol was associated with a higher rate of AVF maturation and a lower rate of AVF-related complications. [ABSTRACT FROM AUTHOR]

We have constructed Fe3O4@BAAH-CuCl nanomagnetic catalyst in ChCl-Urea (choline chloride deep eutectic as solvent) as a highly efficient catalytic system for the preparation of 2-aryl quinazoline derivatives through one-pot, three-component reactions of 2-bromobenzaldehyde with primary amines and sodium azide under molecular oxygen. FT-IR, VSM, SEM, TEM, TGA, XRD, EDX, ICP-OES and elemental mapping analyses confirmed the fabrication of Fe3O4@BAAH-CuCl nanomaterial. In this project, we first prepared various derivatives of benzylamines from reduction of aryl nitriles, then used the benzylamine products as substrates in the three-component synthesis of 2-aryl quinazoline derivatives in the presence of Fe3O4@BAAH-CuCl/ChCl-Urea as an efficient catalytic system. Although the synthesized products (primary amines and 2-aryl quinazolines) were known, their physical state was confirmed with the reported samples in the literature and the structure of all the products confirmed by 1HNMR and 1CNMR. [ABSTRACT FROM AUTHOR]

Nitrogen‐rich energetic materials based on five‐membered azoles, such as tetrazoles, triazoles, oxadiazoles, pyrazoles, and imidazoles, have garnered significant attention in recent years due to their environmental compatibility while maintaining high performance. These materials, including explosives, propellants, and pyrotechnics, are designed to release energy rapidly and efficiently while minimizing the release of toxic or hazardous byproducts and have attracted potential applications in the defense and space industries. The presence of extensive NC, NN, and NN high energy bonds in azoles provides high enthalpies of formation and facilitates intermolecular interactions through π‐stacking which may help with reducing sensitivity to external stimuli. Now, we report on the synthesis and energetic properties of N‐(5‐(1H‐tetrazol‐5‐yl)‐1,3,4‐oxadiazol‐2‐yl)nitramide (5) and its energetic salts. These new high nitrogen–oxygen‐containing materials have attractive feature applications of insensitivity and increased performance. [ABSTRACT FROM AUTHOR]

The activation of muscle pyruvate kinase (PK) increases the conversion of phosphoenolpyruvate (PEP) to pyruvate, which results in the production of ATP. This is critical for supplying the energy needed for muscle contraction. In this study, we synthesized 1,4-dihydropyridine/pyridine compounds bearing tetrazole and 1,3,4-oxadiazole groups by using Hantzsch method and characterized by FT-IR spectroscopy, elemental analysis, and 1H and 13C NMR and studied PK activation, ADME, and molecular docking. The studies revealed that all original synthesized compounds activated PK and AC50 (half-maximal activating concentration) values of the compounds were extremely effective (1.30 µM to 14.65 µM). [ABSTRACT FROM AUTHOR]

Although triazoles and tetrazole are amphoteric and may behave as weak acids, the latter property can be hugely enhanced by beryllium bonds. To explain this phenomenon, the structure and bonding characteristics of the complexes between triazoles and tetrazoles with one and two molecules of BeF2 have been investigated through the use of high-level G4 ab initio calculations. The formation of the complexes between the N basic sites of the azoles and the Be center of the BeF2 molecule and the (BeF2)2 dimer leads to a significant bonding perturbation of both interacting subunits. The main consequence of these electron density rearrangements is the above-mentioned increase in the intrinsic acidity of the azole subunit, evolving from a typical nitrogen base to a very strong nitrogenous acid. This effect is particularly dramatic when the interaction involves the (BeF2)2 dimer, that is, a Lewis acid much stronger than the monomer. Although the azoles investigated have neighboring N-basic sites, their interaction with the (BeF2)2 dimer yields a monodentate complex. However, the deprotonated species becomes extra-stabilized because a second N–Be bond is formed, leading to a new five-membered ring, with the result that the azole-(BeF2)2 complexes investigated become stronger nitrogenous acids than oxyacids such as perchloric acid. [ABSTRACT FROM AUTHOR]

Based on a diazo-coupling process in an aqueous solution under mild conditions, we presented a template-free technique for synthesizing multiple-functionality magnetic porous organic polymers (MOPs) with rich sulfide and free phenolic hydroxyl groups. The resulting pure porous organic polymer (POP) exhibits a large Brunauer–Emmett–Teller (BET) specific surface area of 268.6 m2 g−1, and MOPs have a surface area ranging from 179.91 m2 g−1 to 211.8 m2 g−1. Thermogravimetric analysis (TGA) indicate high thermal stability. Considering the advantages such as their porous nature and abundant adsorption sites, both MOP-F and MOP-H are highly capable of interacting with metal ions and cationic dyes, including methylene blue (MB). The polymers complexed with indium showed excellent catalytic performance for the synthesis of tetrazole derivatives. Moreover, the MOPs exhibited high adsorption capability for the cationic dye methylene blue with a maximum adsorption capacity of 1060 mg g−1. Because of the superparamagnetic properties of the synthesized MOPs, they could be easily separated from the media. The collected MOPs could be reused for four more rounds without a significant decrease in adsorption capacity. [ABSTRACT FROM AUTHOR]

The current research focuses on the design, method development, characterization, and clinical assessment of novel irbesartan medication compounds. The objective of synthetic modification of a drug molecule is to achieve the desired properties such as enhancing the pharmacological properties and minimizing the side effects. It is a biphenyl tetrazole and an aza‐spiro compound, a highly selective, potent nonpeptide compound that belongs to the sartan group, an authorized type‐1 angiotensin II receptor (AT1), dilates the blood vessels and is used in curing of to treat high blood pressure, cardiac arrest, and renal disease in diabetics. To achieve the structural modification of the irbesartan drug, the researcher prepared the FeCl3/SiO2 catalyst and successfully used it for the acetylation, chloro acetylation reaction of irbesartan with acetyl chloride and chloroacetyl chloride. Further, the reaction is performed in presence of the catalyst and without a catalyst to elucidate the role of the catalyst. With the aid of TLC, FT‐IR, and UV–visible spectral methods, the structural interpretation of synthesized derivatives is completed. The present work illustrates a novel method of synthesis of irbesartan derivatives through safe and convenient procedures. The pharmacological evaluation of synthetic derivatives and green chemistry protocol of synthesis is under progress. [ABSTRACT FROM AUTHOR]

Background: Glyoxalase system detoxifies methylglyoxal and other ketoaldehydes to produce innocuous metabolites that allow the cells to function normally. Its inhibition in cancer cells causes these toxic metabolites to accumulate, and the cancer cells enter the apoptotic stage. Methods: The techniques of Computer-Aided Drug Design (CADD) were used, and the compounds possessing a zinc-binding group from commercial databases were extracted, using the pharmacophore search protocol. These compounds were subjected to robust docking using the CDOCKER protocol within the Discovery Studio. Docking was performed on both Glo-I twin active sites. The biological activities of candidate hits were assessed using an in vitro assay against Glo-I. Results: Compounds containing zinc-binding groups were extracted from ASINEX® commercial database, which contains (91,001 compounds). This step has helped to retrieve 1809 ligands, which then were prepared and docked at the two active sites of Glo-I. The fourteen compounds, which have showed the highest scores in docking and returned acceptable Total Binding Energy values, were purchased and tested against the enzyme in vitro. Two compounds out of the fourteen, which were selected in the final step, possess tetrazole ring as zinc chelating moiety, and have showed moderate activity with an IC50 of 48.18μM for SYN 25285236 and 48.77 μM for SYN 22881895. Conclusion: Two hits with moderate activity are identified as the lead compounds against Glo-I. Both compounds possess a negatively ionized tetrazole ring as the zinc-binding moiety. These compounds will lead to the development of inhibitors with improved activities. [ABSTRACT FROM AUTHOR]

The availability of new products and strategies to manage wounds has taken a quantum leap in recent years. Healthcare professionals now have an extensive range of products to choose from, but while positive this also raises dilemmas in real-world clinical practice to decide on the most appropriate treatment for a given patient. Clinical trials confirm the effectiveness of the unique combination of hyaluronic acid and amino acids (Vulnamin®) in a range of wounds, but are these results replicated in real-world clinical practice? International experts presented their clinical experience with the use of the combination in difficult-to-treat wounds. The objective was to reach a consensus on how and when to use the unique combination products to provide a cost-effective, convenient option, in all healthcare settings that improves QoL for patients and their carers. [ABSTRACT FROM AUTHOR]

DTDA‐THA (tris(hydrazin‐1‐ium)5,5′‐(hydrazin‐1‐ide‐1,2‐diylbis((1H‐tetrazole‐5,1‐diyl)))bis(tetrazol‐2‐ide)) is a novel type of poly‐nitrogen energetic material characterized by high nitrogen content, high enthalpy of formation, and low sensitivity. To research the application of DTDA‐THA in polymer‐bonded explosives (PBXs) and improve the safety performance of DTDA‐THA in composite explosives, this study calculated the binding energies between ethylene‐vinyl acetate copolymer (EVA), polyvinyl butyral (PVB), polyvinyl acetate (PVAc) and DTDA‐THA via density functional theory, respectively. Three types of PBXs molding powders were prepared through the direct method. For further investigation, the moisture absorption of molding powders, the forming density, and the compressive strength of the grains under different binders were characterized. The result of the simulation shows higher binding energy between the crystal surface (2 −1 2) and different binders. The comprehensive order of the binding energies between different binders and the crystal surface of DTDA‐THA was DTDA‐THA@EVA>DTDA‐THA@PVB>DTDA‐THA@PVAc. The experimental results show that the addition of binder reduced the hygroscopicity of DTDA‐THA and improved the sensitivity and mechanical properties of the molding powders. Under the same binder proportion, the formulation prepared by PVAc had a higher molding density, while the formulation prepared by PVB exhibited the best compressive strength. [ABSTRACT FROM AUTHOR]

The development of energetic materials with acceptable sensitivity and high energy is a crucial target in explosive research. Primary explosives serve as special metastable energy materials extensively employed in military and civilian activities. Numerous studies are focused on identifying new candidates for this category. However, these newly developed primary explosives often suffer from drawbacks such as the inclusion of heavy metal ions or azide groups, which can lead to environmental concerns and compromised safety levels. In this study, a series of high-energy salts based on nitrogen-rich heterocycles linked by N-methylene-C, which are free from heavy metal ions and azide groups, were designed and synthesized. The molecular structures of the involved compounds were confirmed using single-crystal X-ray diffraction. Additionally, Hirshfeld and independent gradient model analyses of these compounds were conducted to investigate the intermolecular interactions and elucidate the relationship between the interactions and the molecular stabilities. Finally, the thermal stability, energetic properties and electrical initiation properties of compounds 4, 6·2H2O, and 7 were investigated and the results indicate that these compounds are potential primary explosives. [ABSTRACT FROM AUTHOR]

Numerous nitramine bridged compounds which show promising combinations of properties have already been identified in the area of energetic materials. In this work, four new nitrazapropane bridged tetrazoles, as well as four new trinitrazaheptane tetrazoles and three oxapropane bridged tetrazoles were synthesized and fully characterized. These new compounds can all be synthesized by a simple, one‐step synthesis using Finkelstein conditions. All of these new energetic materials were characterized using NMR spectroscopy, single crystal X‐ray diffraction, vibrational analysis and elemental analysis. The thermal behaviour of these compounds was studied by differential thermal analysis (DTA) and partly by thermogravimetric analysis (TGA). The BAM standard method was used to determine the sensitivities towards impact (IS) and friction (FS). The enthalpies of formation were calculated at the CBS‐4M level, and the energetic performances were calculated using the EXPLO5 (V6.06.01) computer code. The properties of the new compounds were compared to each other as well as to the known energetic material RDX. Moreover, the iron(II) and copper(II) perchlorate complexes with 1,3‐bis‐1,1‐tetrazolylnitrazapropane as ligand were prepared and investigated. [ABSTRACT FROM AUTHOR]

In this work, KIT‐6 mesoporous silica material was used to create heterogeneous catalyst due to its excellent surface area, substantial pore volume, and highly functionalized surface. A copper(II) Schiff‐base complex was fabricated on the surface of KIT‐6. For this purpose, (3‐iodopropyl)trimethoxysilane (IPTMS) was synthesized as a linker from (3‐choloropropyl)trimethoxysilane through a simple SN2 reaction using NaI. On the other hand, ligand (a) was synthesized from condensation of diethylenetriamine (DETA) and salicylaldehyde (SA), which was identified by IR and 1H‐NMR techniques. In order to, prepare Sal(PMeOSi)DETA (b), ligand (a) was reacted with IPTMS. One of the challenges of this synthesis was to prove the linkage between the ligand (a) and the IPTMS, which was proved by 1H‐NMR technique. In the next step, the Schiff base complex of copper(Cu(II)[Sal(PMeOSi)DETA]) (c) was synthesized using a complexation reaction of Cu(NO3)2.3 H2O and b. Finally, the obtained copper complex was fixed on KIT‐6, {Cu(II)[Sal(PMeOSi)DETA]} as the new reusable and practical catalyst. This catalyst has been identified using IR, BET, EDS, XRD, SEM, and TGA methods and employed in the synthesis of different tetrazoles for the first time. All tetrazoles were prepared with high yields, and good TOF and TON values, indicating excellent catalytic performance. This catalyst shows excellent homoselectivity in the synthesis of five‐substituted 1H‐tetrazoles. Also, it can be recovered and reused several times without a significant decrease in its catalytic activity or copper leaching. [ABSTRACT FROM AUTHOR]

Three tetrazole-based carboxylic acids, 3,3-di(1H-tetrazol-5-yl)pentanedioic acid (H4L1), 2-(5-pyridin-4-yl-tetrazol-2-yl)propionic anion (HL2), and 5-(2-pyridyl)tetrazole-2-acetic acid (HL3), were selected as ligands to synthesize three new Pb(II)-coordination polymers, [Pb2(L1)] · H2O (1), [Pb(L2)(NO3−)] (2), and [Pb(L3)2(H2O)] · H2O (3). These metal-organic frameworks have been characterized by elemental analysis, FT-IR, and single crystal X-ray diffraction. The results demonstrated that 1 displayed a 3-D network, while 2 and 3 show 2-D framework and 1-D chain, respectively. The differential scanning calorimetry and thermogravimetric analyses gave thermodynamic parameters (ΔH, ΔS, and ΔG). The results showed that 1–3 may be promising high-energy materials. [ABSTRACT FROM AUTHOR]

In order to comprehensively improve the energy performance and combustion properties of the propellants, four energetic metal-organic frameworks (EMOFs) constructed from transition-metal ions (Ag+, Cd2+, Pb2+) and tetrazole-based energetic ligands (5-methyl tetrazole (HMtta), N,N-bis(1H-tetrazole-5-yl)-amine (H2bta), 3-(1H-tetrazol-5-yl)-1H-triazole (H2tztr)) were prepared by hydrothermal synthesis. The crystal phase and structure of the as-prepared samples were analyzed by XRD and IR characterization. Their catalytic activity on thermal decomposition of ammonium perchlorate (AP) was evaluated by DSC. The results show that as-prepared EMOFs can significantly reduce the thermal decomposition temperature of AP and increase its heat release. Under the optimal condition that the addition amount is 10 wt%, the high-temperature decomposition peak temperatures of [AgMtta]n/AP, [Cd5(Mtta)9]n/AP, [Pb3(bta)2(O)2 (H2O)]n/AP, and [Pb(Htztr)2(H2O)]n/AP are decreased by 107.2°C, 94.2°C, 54.6°C, and 91.1°C compared to the case of pure AP, while the heat releases of them are increased by 1243.9 J⋅g-1, 1226.2 J⋅g-1, 1332.2 J⋅g-1, 1444.4 J⋅g-1, respectively. In addition, compared with the reported catalysts such as [Pb(BTF)(H2O)2]n, CuFe2O4, [Cu2(en)2(HBTI)2]2, and [Cu2(en) (HBTI)2]2en, the EMOFs prepared in this study show equal or even higher catalytic activity and heat release. Moreover, the catalytic mechanism of EMOFs on thermal decomposition of AP is also analyzed based on the electron transfer theory. With the excellent energy properties and catalytic performances, the prepared EMOFs may become promising energetic additives for composite solid propellant applications. [ABSTRACT FROM AUTHOR]

In this study, hercynite magnetic nanoparticles (FeAl2O4 MNPs) were synthesized using commercially available materials, including FeCl2.4H2O and Al(NO3)3·9H2O. The surface of FeAl2O4 MNPs was encapsulated using silica and then modified by 3-aminooropropyltrimtoxysilane (APTMS). The modified FeAl2O4 MNPs were further functionalized with tris(hydroxymethyl)amino methane (THAM). Finally, a new copper complex of THAM was stabilized on the surface of functionalized FeAl2O4 MNPs (Cu-THAM@SiO2@FeAl2O4) as a novel, magnetically recoverable, practical, and selective nanocatalyst. The nanocatalyst was characterized using a range of techniques, including atomic absorption spectroscopy (AAS), vibrating-sample magnetometer (VSM), X-ray-mapping analysis, energy dispersive X-ray spectroscopy (EDS), scanning electron microscope (SEM), thermogravimetric analysis (TGA), derivative thermogravimetric (DTG), Fourier transform infrared spectroscopy (FT-IR), and X-ray diffraction (XRD) techniques. The results showed that Cu-THAM@SiO2@FeAl2O4 nanocatalyst was highly efficiency, good selectivity, and excellent reusability in the synthesis of tetrazole derivatives through [3 + 2] cycloaddition of sodium azide (NaN3) with organic nitrile derivatives. [ABSTRACT FROM AUTHOR]

With the critical increase in patients suffering from various types of malignant growth, it is obvious that quick steps in the development of novel and viable agents should be taken. In the current study, we focused on a novel synthetic approach for the synthesis of tetrazole derivatives using Ugi-4CR by employing a gold catalyst in water: methanol media. Gold's adjustable nature, unique characteristics, and mild reaction conditions were utilized to generate a quadrupole adduct containing a cyclohexyl system, benzamine, terminal alkyne bearing aryl and a medicinally efficient tetrazole fragment. Along with the routine characteristic techniques (IR, MS, NMR), single crystal XRD was imparted for the assumption of the spatial arrangement of the desired adduct (5a-5j). Out of 10 selected scaffolds for the NCI 60 cell lines study, 5b was shown their highest potency in the single-dose assay (10−4 M) against CAKI-1 (GI50= −4.66, Renal cancer) and 5e were found to be most active in Leukemia (MOLT-4, GI50= −5.37) cancers than the rest of synthesized molecules. [ABSTRACT FROM AUTHOR]

Kinetic and thermodynamic parameters have been investigated for the thermal Z‒E isomerization of dihydroquinolylazotetrazole dyes with alkyl substituents (Me, t-Bu, and Adm) at positions 1 (dyes 2) and 2 (dyes 3) of the tetrazole moiety in two solvents of different polarity, acetonitrile (MeCN) and toluene. The experimental results show crucial dependence of these parameters on a substituent position in the tetrazole moiety and on a solvent. For dyes 2, Eact and ΔH‡ are lower in MeCN than in toluene that results in a high increase in the lifetimes of the Z isomers: from milliseconds in MeCN to minutes in toluene. For dyes 3, the difference in Eact and ΔH‡ in the two solvents is opposite: Eact and ΔH‡ are by more than 20 kJ mol−1 higher in MeCN, nevertheless, the rate constants for 3 in toluene are comparable with those in MeCN at the ambient temperature and the difference in the behavior is determined by the value of negative entropy of activation. Quantum-chemical calculations of the thermal Z‒E isomerization show the possibility of the process to occur via crossing from the S0 to the thermally induced T1 state. The contribution of this path is highest for 3 in toluene. The analysis of the absorption spectra demonstrates that for the E isomers, the n‒π* and π‒π* transitions are within the long-wavelength absorption band and their positions relative each other are opposite in the solvents: the n‒π* transition is blue-shifted relative to the π‒π* transition in MeCN and is red-shifted in toluene. [ABSTRACT FROM AUTHOR]

Magnesium oxide nanoparticles (NPs) were prepared by a solution combustion method utilizing Terminalia Cuddapha seed extract as fuel, amounting to a greener synthetic protocol. The nano-MgO was characterized by Fourier transform infrared (FT-IR) spectroscopy, powder x-ray diffraction (XRD), scanning electron microscopy (SEM) with energy-dispersive x-ray analysis (EDAX), transmission electron microscopy (TEM), and Brunauer–Emmett–Teller (BET) analysis. The electrical characteristics including dielectric constant, loss tangent, and AC conductivity were measured using a computer-controlled impedance analyser. The dielectric constant and loss tangent were found to decrease as frequency increased. The AC conductivity of the synthesized NPs was steady in the low-frequency region and found to increase as the frequency increased. Finally, the nano-metal oxide was investigated for its ability to effectively catalyse the synthesis of tetrazoles via [2+3] cycloaddition. The tetrazoles thus prepared were fully characterized by mass and nuclear magnetic resonance (NMR) analysis. [ABSTRACT FROM AUTHOR]

The high energy coordination compounds Cu(TZCA)2(ClO4)2 (ECCs-1) was prepared by 1H-tetrazole-5-carbohydrazide (TZCA) with a high energy skeleton and a strong coordination ability group. At the same time, the reaction activity of the ligand was explored, and the single crystal structure of it and intermediate were obtained. The structures of all substances were characterized by IR and EA. And the structure and composition of ECCs-1 are confirmed by ESP, AC, SEM and ICP-OES. Physical and chemical properties tests show that ECCs-1 has an acceptable thermal stability (Td = 177C) and extremely sensitive mechanical stimulation (IS = 1 J, FS = 5 N). The comprehensive performance test results show that ECCs-1 has excellent initiation ability. In addition, the decomposition mechanism of ECCs-1 is explored from two aspects of experiment and theoretical calculation. [ABSTRACT FROM AUTHOR]

Herein, we report an operationally simple and efficient protocol to prepare sulfonyl carbamimidic azide and N‐sulfonyl aminotetrazole via Co‐catalyzed three component coupling of sulfonyl azide (acts as nitrene source), isocyanide, and TMS‐azide at room temperature under visible light. Initially, the carbamimidic azide is formed, which cyclizes only in the presence of base to deliver N‐sulfonyl aminotetrazole in very good yields. The sulfonyl aminotetrazole can also be synthesized directly without isolating the carbamimidic azide in the presence of base. The sulfonyl azide is anticipated to generate nitrene and reacts with isocyanide to produce carbodiimide. Subsequent addition of azide (TMS‐N3) to carbodiimide results in the formation of carbamimidic azide. [ABSTRACT FROM AUTHOR]

Novel hybrids containing 1,2,3-triazole linked tetrazole derivatives were synthesized and characterized by various analytical techniques like 1H, 13C NMR and LC-MS. All the compounds were screened for their anticancer activity against two cancer cell lines A-549 and MCF-7 by using MTT assay and doxorubicin as standard drug. Molecular docking studies were performed on ERK2 using Auto dock Vina of PyRx tool. The binding energies and interactions acquired from docking results of compounds supported the experimental data. [ABSTRACT FROM AUTHOR]

We report herein the syntheses of original pyrazolines and pyrazoles through 1,3‐dipolar cycloaddition of cyclic enones with 2,5‐disubstituted nitrile imines achieved via photochemical activation of 2,5‐diaryl substituted tetrazoles. Monitoring of the reactions, similar to nitrile imine‐mediated tetrazole‐ene cycloadditions (NITEC), could be performed by means of UV‐vis absorption and emission measurements. The presence or absence of substituents in the alpha position of the ketone function makes it possible to direct these reactions towards the selective formation of pyrazoles or pyrazolines. The choice of the cyclic enones and 2,5‐disubstituted tetrazoles proved crucial for the fluorescence properties of the polycyclic derivatives obtained. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Purpose: To assess the antiplatelet effect of cilostazol clinically, we compared the effects of cilostazol in combination with clopidogrel on various platelet function tests. Methods: We recruited patients with ischemic stroke at high risk of recurrence who were treated with clopidogrel alone within 180 days after stroke onset. Subjects underwent baseline platelet function tests, and were then randomly assigned to receive dual antiplatelet therapy (DAPT) comprising clopidogrel and cilostazol or clopidogrel monotherapy (SAPT). After 6 months, platelet function was measured again and compared to that at baseline in each group, and the rate of change was compared between groups. Results: Thirty-four patients were enrolled, but 4 patients were excluded for various reasons. In total, 30 subjects (13 in DAPT and 17 in SAPT group) were analyzed. Adenosine diphosphate- and collagen-induced aggregation, VerifyNow P2Y12 reaction units, vasodilator-stimulated phosphoprotein (platelet reactivity index: PRI) and plasma p-selectin concentration were significantly lower (P = 0.004, 0.042, 0.049, 0.003 and 0.006 respectively), while VerifyNow % inhibition was significantly higher at 6 months compared to baseline (P = 0.003) in the DAPT group only. Comparison of the rate of change in each parameter from baseline to 6 months showed that while PRI decreased at a greater rate (P = 0.012), VerifyNow % inhibition increased at a greater rate (P = 0.003) in the DAPT group than the SAPT group. Conclusions: The inhibitory effects of adjunctive cilostazol added to clopidogrel on platelet function differed by type of platelet function test. VerifyNow % inhibition and PRI were more inhibited than the other platelet function tests. Trial registration: CSPS.com substudy in TWMU (UMIN000026672), registered on April 1, 2017. This study was performed as a substudy of CSPS.com (UMIN000012180, registered on October 31, 2013) and was retrospectively registered. [ABSTRACT FROM AUTHOR]

New nitrogen-containing fusidic acid analogues, namely bis-amidoxime, bis-tetrazole, and 1,2,4-oxadiazoles, were synthesized via chemical transformations of 3,11-bis-O-(2-cyanoethyl)fusidic acid methyl ester. [ABSTRACT FROM AUTHOR]

We herein reported a concise synthesis of a new class of tetrazolyl‐benzothiazoles (TBTs). This synthesis was achieved via a microwave‐assisted ANRORC method followed by an acid‐catalyzed [2 + 3] cycloaddition. The TBT core was elaborated with diverse substituents at the N‐1 or N‐2 position on the tetrazole ring to create a compound library for further bioactivity evaluation. The newly synthesized TBT‐based compounds were assessed for their inhibitory effects against human breast cancer cell lines, MCF‐7 and MDA‐MB‐231. Our results revealed that N‐2 substituted TBTs were generally more active than their N‐1 isomers, and 11g emerged as the most potent inhibitor with IC50 values of 5.3 and 10.4 μg/mL against MCF‐7 and MDA‐MB‐231, respectively. This study provides new insights into the synthesis and anticancer inhibitory activity of TBTs, highlighting their potential for future drug development. [ABSTRACT FROM AUTHOR]

The reaction of dehydroabiethylamine (DHA) with isocyanides and formaldehyde produces varying products depending on the conditions employed. In a 4-component Ugi reaction using benzyl isocyanide, paraformaldehyde, and TMS-azide, the anticipated tetrazole is formed. Nevertheless, other isocyanides were unsuccessful in these conditions. Upon substituting paraformaldehyde with formalin and utilizing ultrasound instead, bis-tetrazole formation was obtained in a pseudo-7-component reaction. A bis-benzyl-substituted tetrazole 5 demonstrated significant AChE and BChE inhibition in Ellman's assays. Molecular modeling corroborated these results, with compound 5 identified as a mixed-type inhibitor for both enzymes.

Lysine malonylation is a recently characterized post-translational modification involved in the regulation of energy metabolism and gene expression. One unique feature of this post-translational modification is its potential susceptibility to decarboxylation, which poses possible challenges to its study. As a step towards addressing these challenges, we report the synthesis and evaluation of a stable isostere of malonyllysine. First, we find that synthetic substitution of the malonyl group with a tetrazole isostere results in amino acids resistant to thermal decarboxylation. Next, we demonstrate that protected variants of this amino acid are readily incorporated into peptides. Finally, we show that tetrazole isosteres of malonyllysine can be recognized by anti-malonyllysine antibodies and histone deacylases, validating their ability to mimic features of the endogenous lysine modification. Overall, this study establishes a new chemical strategy for stably mimicking a metabolite-derived post-translational modification, providing a foothold for tool development and functional analyses.

The tetrazole moiety remains one of the most interesting scaffolds in the development of new high-energy density materials (HEDMs) because of its desired characteristics, such as high nitrogen content and heat of formation (HOF). The combination of several heterocycles with high HOF seems to be a promising strategy for obtaining energetic materials with superior properties. Herein, we report the synthesis and characterization of a tetrazole polymer, polymethylenetetrazole (PMT), as a potential HEDM. The compound was characterized using NMR, IR, and Raman spectroscopy. Its weight average molecular mass was obtained by static light scattering (SLS), and its physical properties by powder XRD analysis. The density, sensitivity to friction (FS), and impact (IS) of the compound were determined as well. The results of the thermal and energetic properties of PMT suggest that this polymer could be an insensitive explosive.

Inappropriate activation of the renin-angiotensin system decreases glucose uptake in peripheral tissues. Chronic angiotensin receptor type 1 (AT1) blockade (ARB) increases glucose uptake in skeletal muscle and decreases the abundance of large adipocytes and macrophage infiltration in adipose. However, the contributions of each tissue to the improvement in hyperglycemia in response to AT1 blockade are not known. Therefore, we determined the static and dynamic responses of soleus muscle, liver, and adipose to an acute glucose challenge following the chronic blockade of AT1. We measured adipocyte morphology along with TNF-α expression, F4/80- and CD11c-positive cells in adipose and measured insulin receptor (IR) phosphorylation and AKT phosphorylation in soleus muscle, liver, and retroperitoneal fat before (T0), 60 (T60) and 120 (T120) min after an acute glucose challenge in the following groups of male rats: 1) Long-Evans Tokushima Otsuka (LETO; lean control; n = 5/time point), 2) obese Otsuka Long Evans Tokushima Fatty (OLETF; n = 7 or 8/time point), and 3) OLETF + ARB (ARB; 10 mg olmesartan/kg/day; n = 7 or 8/time point). AT1 blockade decreased adipocyte TNF-α expression and F4/80- and CD11c-positive cells. In retroperitoneal fat at T60, IR phosphorylation was 155% greater in ARB than in OLETF. Furthermore, in retroperitoneal fat AT1 blockade increased glucose transporter-4 (GLUT4) protein expression in ARB compared with OLETF. IR phosphorylation and AKT phosphorylation were not altered in the liver of OLETF, but AT1 blockade decreased hepatic Pck1 and G6pc1 mRNA expressions. Collectively, these results suggest that chronic AT1 blockade improves obesity-associated hyperglycemia in OLETF rats by improving adipocyte function and by decreasing hepatic glucose production via gluconeogenesis.NEW & NOTEWORTHY Inappropriate activation of the renin-angiotensin system increases adipocyte inflammation contributing to the impairment in adipocyte function and increases hepatic Pck1 and G6pc1 mRNA expression in response to a glucose challenge. Ultimately, these effects may contribute to the development of glucose intolerance.

The electron-induced reactivity of 5-(4-chlorophenyl)-1H-tetrazole and 5-chloro-1-phenyl-1H-tetrazole was studied using a trochoidal electron monochromator quadrupole mass spectrometer experimental setup. 5-(4-chlorophenyl)-1H-tetrazole underwent dissociative electron attachment to form Cl−, [M–HCl]−, and [M–H]−. 5-chloro-1-phenyl-1H-tetrazole underwent associative electron attachment to form the parent anion and dissociative electron attachment to form Cl−, CN2Cl−, [M–N2–Cl]−, and [M–HCl]−. For each anion product, the ion yield was measured as a function of incident electron energy. Density functional theory calculations were performed to support the experimental results with estimates of the energetic thresholds for the different reaction pathways. While the tetrazole group is susceptible to electron-induced ring opening in both molecules, this process was only observed for 5-chloro-1-phenyl-1H-tetrazole, indicating that this process is influenced by the structure of the molecule. [ABSTRACT FROM AUTHOR]

In this study, we develop novel tetrazole compounds based on dibenzyl amine (DBA) and investigate their potential as antioxidants. The aforementioned compounds were synthesised by the Ugi multicomponent reaction, which involved the simultaneous addition of four systems, i.e., DBA, cyclohexyl isocyanide, TMSN3 and aromatic aldehyde in ethanol media under RT. The different isocyanides effect in the progress of the TMSN3 based Ugi reaction was studied. The tetrazoles that were changed with DBA were studied using several techniques, including FTIR, 1H NMR, 13C NMR, and MS. The antioxidant properties of the produced compounds (4a-4j) were subsequently tested in a controlled laboratory setting using the 2,2-diphenyl-1-picryl-hydrazyl-hydrate (DPPH) free radical assay. When compared to ascorbic acid, the antioxidant efficacy of all of the produced compounds was high. The obtained results for all prepared compounds were good as an antioxidant in comparison with ascorbic acid. The electron withdrawing effect of the substituents (halogens and nitro groups) on the aromatic side enhanced the antioxidant activity of the newly derived motifs. Their molecular docking investigation with the myeloperoxidase (MPO) enzyme revealed a strong relationship between their binding modalities and the antioxidant properties they displayed.

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. [ABSTRACT FROM AUTHOR]