Synthesis of thiazolidine-2,4-dione tethered 1,2,3-triazoles as α-amylase inhibitors: In vitro approach coupled with QSAR, molecular docking, molecular dynamics and ADMET studies.

A new series of thiazolidine-2,4-dione tethered 1,2,3-triazole derivatives were designed, synthesized and screened for their α-amylase inhibitory potential employing in vitro and in silico approaches. The target compounds were synthesized with the help of Cu (I) catalyzed [3 + 2] cycloaddition of terminal alkyne with numerous azides, followed by unambiguously characterizing the structure by employing various spectroscopic approaches. The synthesized derivatives were assessed for their in vitro α-amylase inhibition and it was found that thiazolidine-2,4-dione derivatives 6e, 6j, 6o, 6u and 6x exhibited comparable inhibition with the standard drug acarbose. The compound 6e with a 7-chloroquinolinyl substituent on the triazole ring exhibited significant inhibition potential with IC50 value of 0.040 µmol mL-1 whereas compound 6c (IC50 = 0.099 µmol mL-1) and 6h (IC50 = 0.098 µmol mL-1) were poor inhibitors. QSAR studies revealed the positively correlating descriptors that aid in the design of novel compounds. Molecular docking was performed to investigate the binding interactions with the active site of the biological receptor and the stability of the complex over a period of 100 ns was examined using molecular dynamics studies. The physiochemical properties and drug-likeliness behavior of the potent derivatives were investigated by carrying out the ADMET studies.

Synthesis, Characterization and Energetic Properties of Hydroxymethyl-Bishomocubanone Derivatives.

The present work reports synthesis, characterization and theoretical insights on novel hydroxymethyl-bishomocubanone derivatives. Twelve new bishomocubanes (BHCs) were synthesized and fully characterized by various spectroscopic techniques and single crystal X-ray analysis. The densities of the title compounds were found in the range of 1.34-1.59 g/cm3. Density-functional theory (DFT) based calculations at B3LYP/6-311++G(d,p) level of theory were performed on  ten selected BHC based cage compounds. Propulsive and ballistic properties of newly synthesized hydroxymethyl-bishomocubanone derivatives in solid and liquid propulsion systems were calculated, and the results suggested that these compounds are superior to conventional fuel RP1 and binder HTPB. The detonation parameters revealed that these compounds are not explosive in nature and safe to use as solid propellants. Furthermore, kinetic and thermal stabilities of the title compounds were determined by HOMO-LUMO energy gap, ESP maps, impact sensitivity (h50) and bond dissociation energies (BDEs) followed by thermogravimetric analysis (TGA) and differential thermogravimetry analysis (DTA). Three compounds, a dinitroazide (Isp,vac= 310.98s), a dinitrate (Isp,vac = 309.51s), and a dinitronitrate (Isp,vac= 309.20s) were found to be excellent candidates for volume limited applications.

Azidomethyl-bisoxadiazol-linked-1,2,3-triazole-(ABT)-based potential liquid propellant and energetic plasticizer.

A scalable synthesis of azidomethyl bisoxadiazol linked-1,2,3-triazole-(ABT) based potential liquid propellant and energetic plasticizer is obtained from commercially available diaminomaleonitrile in excellent yield. Newly synthesized compounds were fully characterized by various spectroscopic techniques. These materials exhibit good densities (1.77 g cm-3) and high thermal stabilities (Td = 181 °C). Compound 5 has good detonation properties (5, P = 20.81 GPa, D = 7516 ms-1) and propulsive properties (Isp (neat) = 210 s). These are superior to TNT and GAP and comparable to BAMOD, making them potential green liquid rocket propellants and energetic plasticizers.

A versatile beamline for soft x-ray reflectivity, absorption, and fluorescence measurements at Indus-2 synchrotron source.

A versatile beamline for performing reflectivity, fluorescence, and absorption experiments in the soft x-ray region of 100-1500 eV is commissioned on a bending magnet port of the Indus-2 synchrotron source. A high vacuum 2-axis reflectometer with x, y, and z sample scanning stages is installed. This reflectometer is used to measure the reflectivity of large samples up to 300 mm in length and 5 kg in weight. This feature is useful for characterizing x-ray optical elements, such as mirrors, gratings, and multilayers. A flange mounted silicon drift detector is installed in the downstream of the reflectometer for soft x-ray fluorescence measurements. The soft x-ray absorption measurements are carried out in the total electron yield and partial fluorescence yield modes. Integration of three different experimental techniques in the experimental station makes the beamline versatile for materials science applications as it provides structural, chemical, and electronic state information by performing the required experiments in an identical environment. The beamline uses a varied line spacing plane grating monochromator and gives a high flux (∼109 to 1011 photon/s) with a moderate resolution (λ/Δλ ~1000-5000). A three-mirror-based higher harmonic setup is incorporated to get rid of harmonics and to get a high spectral purity monochromatic beam with less than 0.1% harmonic content. In the present article, the beamline optical scheme, mechanical configuration, and details of the experimental setups are presented, along with a few representative results of each experimental mode.

Nitroiminotriazole (NIT) based potential solid propellants: synthesis, characterization, and applications.

Nitroimino (R = N-NO2) energetic material is a unique class of high energy density materials (HEDM). Synthesis and characterization of insensitive nitroimino compounds are a major challenge. Here triazole-based nitroimino compounds and their high-nitrogen green energetic salts in excellent yields are described. These materials exhibit high positive heats of formation (7.84 to 735.29 kJ mol-1), good densities (1.66 to 1.98 g cm-3), suitable detonation properties (P = 22.02 to 31.88 GPa; D = 7472 to 8936 ms-1) and high ballistic properties (Isp 205.66 to 295.35 s; C* = 1065 to 1832 ms-1) with good thermal (Td = 136-378 °C) and mechanical stabilities (IS = 10-40 J and FS = 120-360 N).

Utilization of marine and agro-waste materials as an economical and active food packaging: Antimicrobial, mechanical and biodegradation studies of O-Carboxymethyl chitosan/pectin/neem composite films.

The present work deals with the eco-friendly preparation of highly degradable food packaging films consisting of O-CMC (O-Carboxymethyl Chitosan) and pectin, incorporated with neem (Azadirachta indica) leaves powder and extract. This study aimed to investigate the tensile properties, antimicrobial activity, biodegradability, and thermal behavior of the composite films. The results of tensile strength and elongation at break, showed that the incorporation of neem leaves powder improved the tensile properties (7.11 MPa) of the composite films compared to the neat O-CMC and pectin films (3.02 MPa). The antimicrobial activity of the films was evaluated against a panel of microorganisms including both gram-positive and gram-negative bacteria as well as fungi. The composite films exhibited excellent antimicrobial activity with a zone of inhibition (12-17.6 mm) against the tested microorganisms. The opacity of the composite films ranges from 1.14 to 4.40 mm-1 and the addition of fiber causes a decrease in opacity value. Biodegradability studies were conducted by Soil burial method and the films demonstrated complete biodegradability within 75 days. The results of thermogravimetric analysis (TGA) and differential scanning calorimetry (DSC) of composite films show that they are thermally stable and might be used in food packaging.

CORAL: probing the structural requirements for α-amylase inhibition activity of 5-(3-arylallylidene)-2-(arylimino)thiazolidin-4-one derivatives based on QSAR with correlation intensity index, molecular docking, molecular dynamics, and ADMET studies.

The present study aims to examine the structural requirements governing α-amylase inhibitory activity of 5-(3-arylallylidene)-2-(arylimino)thiazolidin-4-one derivatives and their precursors by employing a multifaceted approach combining in vitro and in silico studies. The in vitro assay findings revealed strong inhibitory effect of this class of compounds against α-amylase and compound 20 exhibited maximum percentage inhibition of 88.54 ± 0.69, 84.98 ± 0.40, 77.26 ± 0.75, 67.80 ± 0.54, and 62.93 ± 1.17 at 200, 100, 50, 25, and 12.5 µg mL-1, respectively. Multiple CORAL QSAR models were developed from the randomly distributed eight splits by employing two target functions (TF1, TF2 with WCII = 0.0 and = 0.3, respectively), and the quality of predictions by the produced models was validated with the help of various statistical parameters. The model M-4 (R2Val = 0.8799) and model M-11 (R2Val = 0.9064) were the leading models developed by using TF1 and TF2. We designed five new congeneric inhibitors (D-1 to D-5) by incorporating SMILES features positively correlating with the activity. Molecular docking experiments were carried out to confirm the binding of these new inhibitors with the biological receptor α-amylase (PDB ID: 7TAA). Furthermore, molecular dynamic simulations provided a thorough knowledge of the binding process by shedding insight into the dynamic behavior and stability of the ligand-receptor complex over time. The results of this study highlight the key structural characteristics needed for improved α-amylase inhibitory efficacy and provide a rational basis for the development of more effective inhibitors.Communicated by Ramaswamy H. Sarma.

Energetic performance of trinitromethyl nitrotriazole (TNMNT) and its energetic salts.

Little is known about trinitromethyl nitrotriazole (TNMNT) since the crystal structure, density, energetic performance, and thermal properties have not been determined. A detailed characterization of TNMNT and its hydrazinium and potassium salts and their potential as solid propellants and oxidizers has been established. TNMNT exhibits a high density (1.96 g cm-3) and positive enthalpy of formation (ΔHf = +84.79 kJ mol-1). TNMNT and its hydrazinium and potassium salts illustrate excellent detonation properties (P = 34.24 to 36.22 GPa, D = 8899 to 9031 ms-1). TNMNT and its hydrazinium salt exhibit outstanding propulsive properties (Isp = 247.28 to 271.19 s), and these are superior to AP (Isp = 156.63 s) and ADN (Isp = 202.14 s). The results suggest opening the door to utilizing TNMNT and its energetic salts in solid rocket propulsion.

α-amylase inhibition and in silico studies of novel naphtho[2,3-d]imidazole-4,9-dione linked N-acyl hydrazones.

Aim: To enrich the pool of α-amylase inhibitors to manage Type 2 diabetes. Methods: Synthesis, conformational study, α-amylase inhibitory action and various in silico studies of novel N'-(arylbenzylidene)-2-(4,9-dioxo-4,9-dihydro-1H-naphtho[2,3-d]imidazol-1-yl)acetohydrazides carried out. Results: Compound H6 demonstrated the highest activity (IC50 = 0.0437 µmol mL-1) among the tested compounds. Structure-activity relationship study suggested that variable substitution at the aryl ring has a pivotal role in determining the inhibitory action of tested compounds. Docking simulations of the most active compound (H6) confirmed its interaction potential with active site residues of A. oryzae α-amylase. The root-mean-square deviation fluctuations substantiated the stability of protein-ligand complex. Absorption, distribution, metabolism and excretion prediction revealed optimal values for absorption, distribution, metabolism and excretion parameters. Conclusion: The developed molecules could be beneficial for the development of novel α-amylase inhibitors to treat Type 2 diabetes.

Trinitromethyl-triazolone (TNMTO): a highly dense oxidizer.

A scalable synthesis of 5-(trinitromethyl)-2,4-dihydro-3H-1,2,4-triazol-3-one (TNMTO) is possible from commercially available 2-methylpyrimidine-4,6-diol. It exhibits high density (1.90 g cm-3) with comparably low thermal stability (Td = 80 °C) and positive oxygen balance (OBco = 20.51%, OBCO2 = 0.0%). TNMTO has an attractive combination of detonation properties (P = 35.01 GPa, D = 8997 ms-1) and propulsive properties (Isp(neat) = 251.85 s, ρIsp(neat) = 478.52 gs cm-3, ). These are superior to ammonium dinitroamide (ADN), 2,2,2-tetranitroacetimidic acid (TNAA) and ammonium perchlorate (AP), making it a potential green oxidizer in solid rocket propulsion.

Thiazolidinedione-triazole conjugates: design, synthesis and probing of the α-amylase inhibitory potential.

Aim: The primary objective of this investigation was the synthesis, spectral interpretation and evaluation of the α-amylase inhibition of rationally designed thiazolidinedione-triazole conjugates (7a-7aa). Materials & methods: The designed compounds were synthesized by stirring a mixture of thiazolidine-2,4-dione, propargyl bromide, cinnamaldehyde and azide derivatives in polyethylene glycol-400. The α-amylase inhibitory activity of the synthesized conjugates was examined by integrating in vitro and in silico studies. Results: The investigated derivatives exhibited promising α-amylase inhibitory activity, with IC50 values ranging between 0.028 and 0.088 µmol ml-1. Various computational approaches were employed to get detailed information about the inhibition mechanism. Conclusion: The thiazolidinedione-triazole conjugate 7p, with IC50 = 0.028 µmol ml-1, was identified as the best hit for inhibiting α-amylase.

Design and Synthesis of High-Performance Planar Explosives and Solid Propellants with Tetrazole Moieties.

A straightforward synthetic strategy for newly designed nitrogen-rich planar explosives and solid propellants is reported. These materials exhibit high densities (1.69-1.95 g cm-3), high positive enthalpies of formation (approaching 1149.21 kJ mol-1), promising energetic properties (P = 26.36-33.78 GPa, D = 8258-9518 m s-1), acceptable thermal stabilities (Td = 132-277 °C), good sensitivities (IS = 4-40 J, FS = 60-360 N) and excellent propulsive performance (Isp = 176.80-253.06 s).

Parsing structural fragments of thiazolidin-4-one based α-amylase inhibitors: A combined approach employing in vitro colorimetric screening and GA-MLR based QSAR modelling supported by molecular docking, molecular dynamics simulation and ADMET studies.

α-Amylase (EC.3.2.1.1) is a ubiquitous digestive endoamylase. The abrupt rise in blood glucose levels due to the hydrolysis of carbohydrates by α-amylase at a faster rate is one of the main reasons for type 2 diabetes. The inhibitors prevent the action of digestive enzymes, slowing the digestion of carbs and eventually assisting in the management of postprandial hyperglycemia. In the course of developing α-amylase inhibitors, we have screened 2-aryliminothiazolidin-4-one based analogs for their in vitro α-amylase inhibitory potential and employed various in silico approaches for the detailed exploration of the bioactivity. The DNSA bioassay revealed that compounds 5c, 5e, 5h, 5j, 5m, 5o and 5t were more potent than the reference drug (IC60 value = 22.94 ± 0.24 µg mL-1). The derivative 5o with -NO2 group at both the rings was the most potent analog with an IC60 value of 19.67 ± 0.20 µg mL-1 whereas derivative 5a with unsubstituted aromatic rings showed poor inhibitory potential with an IC60 value of 33.40 ± 0.15 µg mL-1. The reliable QSAR models were developed using the QSARINS software. The high value of R2ext = 0.9632 for model IM-9 showed that the built model can be applied to predict the α-amylase inhibitory activity of the untested molecules. A consensus modelling approach was also employed to test the reliability and robustness of the developed QSAR models. Molecular docking and molecular dynamics were employed to validate the bioassay results by studying the conformational changes and interaction mechanisms. A step further, these compounds also exhibited good ADMET characteristics and bioavailability when tested for in silico pharmacokinetics prediction parameters.

Design and synthesis of phenylene-bridged isoxazole and tetrazole-1-ol based energetic materials of low sensitivity.

A variety of phenylene-bridged isoxazole and tetrazole-1-ol based green energetic materials was synthesized, for the first time, in good to excellent yields. The structures of the newly synthesized compounds were confirmed by spectroscopic techniques, elemental analysis, and single-crystal X-ray analysis. The value of the present work is that all newly synthesized compounds have good thermal stabilities ranging between 167-340 °C and acceptable densities between 1.51 g cm-3 to 1.82 g cm-3. Detailed computational insight into the energetic properties of the new compounds shows that they have good energetic properties (propulsive and ballistic) with excellent thermal and mechanical stabilities which makes them promising candidates for solid propulsion systems. Compounds 5, 12 and 14 are the superior candidates as melt-castable energetic materials.

Correction: Dhatwalia et al. Rubus ellipticus Sm. Fruit Extract Mediated Zinc Oxide Nanoparticles: A Green Approach for Dye Degradation and Biomedical Applications. Materials 2022, 15, 3470.

In the original publication [...].

Approaches to 1,4-Disubstituted Cubane Derivatives as Energetic Materials: Design, Theoretical Studies and Synthesis.

Novel 1,4-disubstituted cubane derivatives have been designed and selected ones have been successfully synthesized and characterized by various analytical and spectroscopic techniques, including single-crystal X-ray analysis. A detailed computational study at B3LYP/6-311++G(d,p) level of theory revealed that all newly designed 1,4-disubstituted cubane derivatives possess higher densities, higher density-specific impulse and superior ballistic properties when compared to conventional fuels, for example, RP-1. These compounds also exhibit acceptable kinetic and thermodynamic stabilities which were evaluated in terms of their HOMO-LUMO energy gap and bond dissociation energies, respectively, and are superior to TEX and many other compounds containing explosophoric groups. These results provide novel insights into the possible application of cubane-based energetic materials.

Rubus ellipticus Sm. Fruit Extract Mediated Zinc Oxide Nanoparticles: A Green Approach for Dye Degradation and Biomedical Applications.

Rubus ellipticus fruits aqueous extract derived ZnO-nanoparticles (NPs) were synthesized through a green synthesis method. The structural, optical, and morphological properties of ZnO-NPs were investigated using XRD, FTIR, UV-vis spectrophotometer, XPS, FESEM, and TEM. The Rietveld refinement confirmed the phase purity of ZnO-NPs with hexagonal wurtzite crystalline structure and p-63-mc space group with an average crystallite size of 20 nm. XPS revealed the presence of an oxygen chemisorbed species on the surface of ZnO-NPs. In addition, the nanoparticles exhibited significant in vitro antioxidant activity due to the attachment of the hydroxyl group of the phenols on the surface of the nanoparticles. Among all microbial strains, nanoparticles' maximum antibacterial and antifungal activity in terms of MIC was observed against Bacillus subtilis (31.2 µg/mL) and Rosellinia necatrix (15.62 µg/mL), respectively. The anticancer activity revealed 52.41% of A549 cells death (IC50: 158.1 ± 1.14 µg/mL) at 200 µg/mL concentration of nanoparticles, whereas photocatalytic activity showed about 17.5% degradation of the methylene blue within 60 min, with a final dye degradation efficiency of 72.7%. All these results suggest the medicinal potential of the synthesized ZnO-NPs and therefore can be recommended for use in wastewater treatment and medicinal purposes by pharmacological industries.

Regio- and stereoselective synthesis of functionalized and fused heterocycles from Morita-Baylis-Hillman adducts of dicyclopentadienone.

An efficient protocol for the Morita-Baylis-Hillman (MBH) reaction of dicyclopentadienone using CTAB has been developed. The MBH adduct was subsequently transformed to its acetate and bromide derivatives. The 1,3-bielectrophilic character of the MBH acetate and bromide was further explored with various 1,3-binucleophiles to construct various oxa-, thia- and aza-heterocycles. These reactions proceed through a cascade double Michael addition of 1,3-binucleophiles to the MBH acetate/bromide under basic conditions. Amenability of these reactions to scale-up and applications of the products in the synthesis of cyclopentenone-fused chromenones and thiopyranoindoles have been demonstrated.

Sonochemical Protocols for Heterocyclic Synthesis: A Representative Review.

In the present era of the industrial revolution, we all are familiar with ever-increasing environmental pollution released from various chemical processes. Chemical production has had a severe impact on the environment and human health. For the betterment of our environment, the chemical community has turned their interest to developing green, harmless and sustainable synthetic processes. To accomplish these goals of green chemistry, the extraordinary properties of sonication play an important role. It is well known that sonochemistry can make decisive contributions to creating high pressures of almost 1000 atm and very high temperatures in the range of 4500-5000 °C. The implementation of ultrasound in chemical transformations somehow fulfils the measures of green chemistry, as it reduces energy consumption, enhances product selectivity, and uses lesser amounts of hazardous chemicals and solvents. Furthermore, heterocyclic synthesis under ultrasonication offers several environmental and process-related advantages compared with conventional methods. The remarkable contribution of ultrasonics to the development of green and sustainable synthetic routes inspired us to write this article. Herein, we have discussed only some of the various synthetic methodologies developed for the construction of heterocyclic cores under ultrasonic irradiation, accompanied by mechanistic insights. In some cases, a comparison between sonochemical conditions and conventional conditions has also been investigated. We emphasized principally 'up to date' developments on various sono-accelerated chemical transformations comprising aza-Michael, aldol reactions, C-C couplings, oxidation, cycloadditions, multi-component reactions, etc. for the synthesis of heterocycles.

Quantitative structure activity relationship studies of novel hydrazone derivatives as α-amylase inhibitors with index of ideality of correlation.

The present manuscript describes the synthesis, α-amylase inhibition, in silico studies and in-depth quantitative structure-activity relationship (QSAR) of a library of aroyl hydrazones based on benzothiazole skeleton. All the compounds of the developed library are characterized by various spectral techniques. α-Amylase inhibitory potential of all compounds has been explored, where compound 7n exhibits remarkable α-amylase inhibition of 87.5% at 50 µg/mL. Robust QSAR models are made by using the balance of correlation method in CORAL software. The chemical structures at different concentration with optimal descriptors are represented by SMILES. A data set of 66 SMILES of 22 hydrazones at three distinct concentrations are prepared. The significance of the index of ideality of correlation (IIC) with applicability domain (AD) is also studied at depth. A QSAR model with best Rvalidation2 = 0.8587 for split 1 is considered as a leading model. The outliers and promoters of increase and decrease of endpoint are also extracted. The binding modes of the most active compound, that is, 7n in the active site of Aspergillus oryzae α-amylase (PDB ID: 7TAA) are also explored by in silico molecular docking studies. Compound 7n displays high resemblance in binding mode and pose with the standard drug acarbose. Molecular dynamics simulations performed on protein-ligand complex for 100 ns, the protein gets stabilised after 20 ns and remained below 2 Å for the remaining simulation. Moreover, the deviation observed in RMSF during simulation for each amino acid residue with respect to Cα carbon atom is insignificant.