Ultrafast synthesis of efficient TS-PtCoCu/CNTs composite with high feed-to-product conversion rate by Joule heating for electrocatalytic oxidation of ethanol.

Due to the challenges involved in achieving high metal load, uniform metal dispersion and nanosized metal particles simultaneously, it is difficult to develop a simple protocol for the rapid and efficient synthesis of Pt-based composites for electrocatalytic ethanol oxidation reaction (EOR). In this study, a facile ultrafast thermal shock strategy via Joule heating was applied to fabricate a series of PtCoCu ternary nanoalloys decorated carbon nanotube composites (TS-PtCoCu/CNTs), without the need for a reducing agent or surfactant. The TS-PtCoCu/CNTs with optimal Pt content (∼15 %) exhibited excellent EOR activity, with mass and specific activity of 3.58 A mgPt-1 and 5.79 mA cm-2, respectively, which are 3.8 and 13.5 times higher than those of Pt/C. Compared with the control prepared through the traditional furnace annealing, the catalyst also showed excellent activity and stability. DFT calculations revealed that the TS-PtCoCu/CNTs possesses a downshifted d-band center, weakened CO adsorption and higher OH affinity compared with monometallic Pt, all of which lead to the preferred C1 pathway for EOR. This study demonstrates an ultrafast construction of a highly efficient Pt-Co-Cu ternary catalyst for EOR. Additionally, it provides insights into the reaction mechanism based on structural characterization, electrochemical characterization, and theoretical calculations.

A Combined Experimental and Computational Study of Novel Benzotriazinone Carboxamides as Alpha-Glucosidase Inhibitors.

Diabetes is a chronic metabolic disorder of the endocrine system characterized by persistent hyperglycemia appears due to the deficiency or ineffective use of insulin. The glucose level of diabetic patients increases after every meal and medically recommended drugs are used to control hyperglycemia. Alpha-glucosidase inhibitors are used as antidiabetic medicine to delay the hydrolysis of complex carbohydrates. Acarbose, miglitol, and voglibose are commercial drugs but patients suffer side effects of flatulence, bloating, diarrhea, and loss of hunger. To explore a new antidiabetic drug, a series of benzotriazinone carboxamides was synthesized and their alpha-glucosidase inhibition potentials were measured using in vitro experiments. The compounds 14k and 14l were found to be strong inhibitors compared to the standard drug acarbose with IC50 values of 27.13 ± 0.12 and 32.14 ± 0.11 µM, respectively. In silico study of 14k and 14l was carried out using molecular docking to identify the type of interactions developed between these compounds and enzyme sites. Both potent compounds 14k and 14l exhibited effective docking scores by making their interactions with selected amino acid residues. Chemical hardness and orbital energy gap values were investigated using DFT studies and results depicted affinity of 14k and 14l towards biological molecules. All computational findings were found to be in good agreement with in vitro results.

Investigations of Electronic, Structural, and In Silico Anticancer Potential of Persuasive Phytoestrogenic Isoflavene-Based Mannich Bases.

Isoflavenes have received the greatest research attention among the many groups of phytoestrogens. In this study, various isoflavene-based Mannich bases were selected for their theoretical studies. The purpose of this research was to discover the binding potential of all the designated Mannich bases acting as inhibitors against cancerous proteins EGFR, cMet, hTrkA, and HER2 (PDB codes: 5GTY, 3RHK, 6PL2, and 7JXH, respectively). For their virtual screening, DFT calculations and molecular docking studies were undertaken using in silico software. Docking studies predicted that ligands 5 and 15 exhibited the highest docking score by forming hydrogen bonds within the active pocket of protein 6PL2, ligands 1 and 15 both with protein 3RHK, and 7JXH, 12, and 17 with protein 5GTY. Rendering to the trends in polarizability and dipole moment, the energy gap values (0.2175 eV, 0.2106 eV) for the firm conformers of Mannich bases (1 and 4) replicate the increase in bioactivity and chemical reactivity. The energy gap values (0.2214 eV and 0.2172 eV) of benzoxazine-substituted isoflavene-based Mannich bases (9 and 10) reflect the increase in chemical potential due to the most stable conformational arrangements. The energy gap values (0.2188 eV and 0.2181 eV) of isoflavenes with tertiary amine-based Mannich bases (14 and 17) reflect the increase in chemical reactivity and bioactivity due to the most stable conformational arrangements. ADME was also employed to explore the pharmacokinetic properties of targeted moieties. This study revealed that these ligands have a strong potential to be used as drugs for cancer treatment.

Design, Synthesis, Characterization and Computational Studies of Mannich Bases Oxadiazole Derivatives as New Class of Jack Bean Urease Inhibitors.

Mannich bases consisting of 1,3,4-oxadiazole-2-thione (3 a-3 l) bearing various substituents were synthesized and found potent jack bean urease inhibitors. The prepared compounds showed significantly good inhibitory activities with IC50 values from 9.45±0.05 to 267.42±0.23 µM. The compound 3 k containing 4-chlorophenyl (-R) and 4-hydroxyphenyl (-R') was most active with IC50 9.45±0.05 µM followed by 3 e (IC50 22.52±0.15 µM) in which -R was phenyl and -R' was isopropyl group. However, when both -R and -R' were either 4-chlorophenyl groups (3 l) or only -R' was 4-nitrophenyl (3 i), both compounds were found inactive. The detailed binding affinities of the produced compounds with protein were explored through molecular docking and data-supported in-vitro enzyme inhibition profiles. Drug likeness was confirmed by in silico ADME investigations and molecular orbital analysis (HOMO-LUMO) and electrostatic potential maps were got from DFT calculations. ESP maps exposed that there are two potential binding sites with the most positive and most negative parts.

Aqueous extract of Platycodon grandiflorus attenuates lipopolysaccharide-induced apoptosis and inflammatory cell infiltration in mouse lungs by inhibiting PI3K/Akt signaling.

BACKGROUND: Acute lung injury (ALI), an acute inflammatory lung disease, can cause a rapid inflammatory response in clinic, which endangers the patient's life. The components of platycodon grandiflorum, such as platycodins have a wide range of pharmacological activities such as expectorant, anti-apoptotic, anti-inflammatory, anti-tumor and anti-oxidant properties, and can be used for improving human immunity. Previous studies have shown that aqueous extract of platycodon grandiflorum (PAE) has a certain protective effect on ALI, but the main pharmacodynamic components and the mechanism of action are not clear. METHODS: The anti-inflammatory properties of PAE were studied using the lipopolysaccharide (LPS)-induced ALI animal model. Hematoxylin and eosin stains were used to assess the degree of acute lung damage. Changes in RNA levels of pro-inflammatory cytokines in the lungs were measured using quantitative RT-qPCR. The potential molecular mechanism of PAE preventing ALI was predicted by lipidomics and network pharmacology. To examine the anti-apoptotic effects of PAE, TdT-mediated dUTP nick-end labelling (TUNEL) was employed to determine apoptosis-related variables. The amounts of critical pathway proteins and apoptosis-related proteins were measured using Western blotting. RESULTS: Twenty-six chemical components from the PAE were identified, and their related pathways were obtained by the network pharmacology. Combined with the analysis of network pharmacology and literature, it was found that the phosphatidylinositol 3 kinase (PI3K)/protein kinase B (AKT) signaling pathway is related to ALI. The results of lipidomics show that PAE alleviates ALI via regulating lung lipids especially phosphatidylinositol (PI). Finally, the methods of molecular biology were used to verify the mechanism of PAE. It can be found that PAE attenuates the inflammatory response to ALI by inhibiting apoptosis through PI3K/Akt signaling pathway. CONCLUSION: The study revealed that the PAE attenuates lipopolysaccharide-induced apoptosis and inflammatory cell infiltration in mouse lungs by inhibiting PI3K/Akt signaling. Furthermore, our findings provide a novel strategy for the application of PAE as a potential agent for preventing patients with ALI.

Facile Synthesis of ZIF-67 for the Adsorption of Methyl Green from Wastewater: Integrating Molecular Models and Experimental Evidence to Comprehend the Removal Mechanism.

Organic dyes with enduring colors which are malodorous are a significant source of environmental deterioration due to their virulent effects on aquatic life and lethal carcinogenic effects on living organisms. In this study, the adsorption of methyl green (MG), a cationic dye, was achieved by using ZIF-67, which has been deemed an effective adsorbent for the removal of contaminants from wastewater. The characterization of ZIF-67 was done by FTIR, XRD, and SEM analysis. The adsorption mechanism and characteristics were investigated with the help of control batch experiments and theoretical studies. The systematical kinetic studies and isotherms were sanctioned with a pseudo-second-order model and a Langmuir model (R2 = 0.9951), confirming the chemisorption and monolayer interaction process, respectively. The maximum removal capacities of ZIF-67 for MG was 96% at pH = 11 and T = 25 °C. DFT calculations were done to predict the active sites in MG by molecular electrostatic potential (MEP). Furthermore, both Molecular dynamics and Monte Carlo simulations were also used to study the adsorption mechanism.

Synthesis and Micromechanistic Studies of Sensitized Bentonite for Methyl Orange and Rhodamine-B Adsorption from Wastewater: Experimental and DFT-Based Analysis.

This work reports the formation of a novel adsorbent, prepared by activating bentonite with cinnamic acid, which is highly efficient to remove dyes from wastewater. The adsorption efficiency of the cinnamic acid activated bentonite was compared with unmodified bentonite by removing methyl orange and rhodamine-B from polluted water. The characterization was performed through X-ray diffraction (XRD) Fourier transform infrared (FTIR) and scanning electron microscopy (SEM). The results indicated that acidic pH and low temperature were more suitable for the selected dyes adsorption. The analysis of the data was done by the Langmuir and Freundlich isotherms; the Freundlich isotherm showed more suitability for the equilibrium data. The data were further analyzed by pseudo-first and pseudo-second-order models to study adsorption kinetics. The results showed that methyl orange and rhodamine-B adsorption obeyed pseudo-order kinetics. The results obtained from this research suggested that acid activation of bentonite with cinnamic acid increased the surface area of the clay and hence enhanced its adsorption efficiency. The maximum adsorption efficiency for the removal of methyl orange and rhodamine-B was up to 99.3 mg g-1 and 44.7 mg g-1, respectively, at 25 °C. This research provides an economical modification technique of bentonite, which makes it cost-effective and a good adsorbent for wastewater treatment.

Synthesis, in Vitro Cholinesterase Inhibition, Molecular Docking, DFT, and ADME Studies of Novel 1,3,4-Oxadiazole-2-Thiol Derivatives.

A series of 1,3,4-oxadiazole-2-thiol derivatives bearing various alkyl or aryl moieties were designed, synthesized, and characterized using modern spectroscopic methods to yield 17 compounds (6a-6q) that were screened for acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) enzymes in the search for 'lead' compounds for Alzheimer's disease treatment (AD). The compounds 6q, 6p, 6k, 6o, and 6l showed inhibitory capability against AChE and BChE, with IC50 values ranging from 11.73±0.49 to 27.36±0.29 µM for AChE and 21.83±0.39 to 39.43±0.44 µM for BChE, inhibiting both enzymes within a limited range. The SAR ascertained that the substitution of the aromatic moiety had a profound effect on the AChE and BChE inhibitory potential as compared to the aliphatic substitutions which were supported by the molecular docking studies. The drug-likeness of the most synthesized compounds was confirmed by in silico ADME investigations. These results were additionally supplemented by the molecular orbital analysis (HOMO-LUMO) and electrostatic potential maps got from DFT calculations. ESP maps expose that on all structures, there are two potential binding sites conquered by the most positive and most negative districts.

Organocatalyzed Solvent Free and Efficient Synthesis of 2,4,5-Trisubstituted Imidazoles as Potential Acetylcholinesterase Inhibitors for Alzheimer's Disease.

The catalytic potential of pyridine-2-carboxlic acid has been evaluated for efficient, green and solvent free synthesis of 2,4,5-trisubstituted imidazole derivatives 3a-3m. The compounds 3a-3m were synthesized by one pot condensation reaction of substituted aromatic aldehydes, benzil, and ammonium acetate in good to excellent yields (74-96 %). To explore the potential of these compounds against Alzheimer's disease, their inhibitory activities against acetylcholinesterase (AChE) were evaluated. In this series of compounds, compound 3m, bearing one ethoxy and a hydroxy group on the phenyl ring on 2,4,5-trisubstituted imidazoles, proved to be a potent AChE inhibitor (102.56±0.14). Structure-activity relationship (SAR) of these compounds was developed. Molecular dockings were carried out for the compounds 3m, 3e, 3k, 3c, 3a, 3d, 3j, and 3f in order to further investigate the binding mechanism. The inhibitor molecule was molecularly docked with acetylcholinesterase to further study its binding mechanism. The amino group of the compound 3m forms an H-bond with the oxygen atom of the residue (i. e., THR121) which has a bond length of 3.051 Å.

Facile one-step economical methodology of metal free g-C3N4 synthesis with remarkable photocatalytic performance under visible light to degrade trans-resveratrol.

Nanoropes crafted graphitic carbon nitride (NRCN-2), prepared by a novel, cost effective and easy to scale up method. We used naphthalene to induce nanoropes like structure inside of the graphitic carbon nitride; on industrial scale, it is easy to recycle naphthalene. The Naphthalene decomposition temperature (>700 °C) is much higher than the polymerization temperature ( = 520 °C) of NRCN-2. At higher temperature, naphthalene molecular vapors moved vigorously through graphitic carbon nitride sheets and caused the sheets to adopt nanoropes like morphology. Photocatalyst (NRCN-2) presented extraordinary specific surface area (351.08 m2 g-1), stimulated the parting effectiveness of photo-generated electrons and holes, by extending the visible light harvesting ability to 600 nm. The nanoropes adopted photocatalysts can easily degrade MO in 90 min and trans-resveratrol in 120 min. The buoyant energetic reactive species (h+, OH and O2-), created during photocatalysis caused mineralization of pollutants. The apparent rate constant, half-life time period and regression coefficients for MO and trans-resveratrol calculated with the help of pseudo first order kinetics. For MO the value of Kapp is 2.968 × 10-2 min-1, for trans-resveratrol, Kapp is 2.490 × 10-2 min-1, corresponding half-life values are 23.354 min and 27.837 min respectively.

Sensitization of TiO2 nanosheets with Cu-biphenylamine framework to enhance photocatalytic degradation performance of toxic organic contaminants: synthesis, mechanism and kinetic studies.

TNS/Cu(X) composite materials were firstly synthesized via simple overnight stirring of TNS in the methanolic solution of Cu complexes. The developed TNS/Cu(X) composites had a well-designed nanostructure, in which the TNS and Cu complexes were closely bounded with each other. The biphenylamine complexes fixed on the TNS surface in form of nanocapsules, which were confirmed by TEM and SEM, thus improving the surface area and subsequently charge separation. Innovatively merged photocatalysts of Cu complexes with TNS were successfully verified for photocatalytic mineralization of colored and colorless organic contaminants under the visible light degradation. As compared to original TNS, TNS/Cu(BA) showed prominent improvement in the catalytic actions. Kinetics i.e. t 1/2 (half-life times period), K app, and R 2 (linear regression co-efficient) were also studied. The amended materials created charge separation, by means of electrons gathering at the higher CB, and holes gathering at the lower level valence band of the Cu complex, therefore improving mineralization efficiency of the electrons and holes. TNS/Cu(BA) degrade 99%-99.6% of methyl orange (MO) and rhodamine B (RhB) dyes at 120 min, and 160 min, respectively, and 68% of phenol and 53% of TCP were destroyed in 180 min. The resilient holes can directly destroy MO, RhB, phenol, and TCP.

Organocatalyzed and mechanochemical solvent-free synthesis of novel and functionalized bis-biphenyl substituted thiazolidinones as potent tyrosinase inhibitors: SAR and molecular modeling studies.

Eluding the involvement of solvents in organic synthesis and introducing environment friendly procedures can control environmental problems. A facile and an efficient solvent free mechanochemical method (grinding) is achieved to synthesize novel bis-biphenyl substituted thiazolidinones using non-toxic and cheap N-acetyl glycine (NAG). Organocatalytic condensation of a series of Schiff's bases bearing different substituents with thioglycolic acid produces a variety of thiazolidinones derivatives in good to excellent yield. In vitro inhibition studies against mushroom tyrosinase of these thiazolidinone analogues revealed that many of them possessed good to excellent tyrosinase inhibition at low micro-molar concentrations. In particular, six compounds exhibited potent inhibitory potential with IC50 values ranging from 0.61 ± 0.31 to 21.61 ± 0.11 µM as compared with that of standard kojic acid (IC50 6.04 ± 0.11 µM). Further molecular docking studies revealed that the thiazolidinones moiety plays a key role in the inhibition mechanism by well fitting into the enzyme bounding pocket.

Novel biphenyl bis-sulfonamides as acetyl and butyrylcholinesterase inhibitors: Synthesis, biological evaluation and molecular modeling studies.

A series of new biphenyl bis-sulfonamide derivatives 2a-3p were synthesized in good to excellent yield (76-98%). The inhibitory potential of the synthesized compounds on acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) was investigated. Most of the screened compounds showed modest in vitro inhibition for both AChE and BChE. Compared to the reference compound eserine (IC50 0.04 ± 0.0001 µM for AChE) and (IC50 0.85 ± 0.0001 µM for BChE), the IC50 values of these compounds were ranged from 2.27 ± 0.01 to 123.11 ± 0.04 µM for AChE and 7.74 ± 0.07 to <400 µM for BuChE. Among the tested compounds, 3p was found to be the most potent against AChE (IC50 2.27 ± 0.01 µM), whereas 3g exhibited the highest inhibition for BChE (IC50 7.74 ± 0.07 µM). Structure-activity relationship (SAR) of these compounds was developed and elaborated with the help of molecular docking studies.

Pyridine sulfonamide as a small key organic molecule for the potential treatment of type-II diabetes mellitus and Alzheimer's disease: In vitro studies against yeast α-glucosidase, acetylcholinesterase and butyrylcholinesterase.

This paper presents the efficient high yield synthesis of novel pyridine 2,4,6-tricarbohydrazide derivatives (4a-4i) along with their α-glucosidase, acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibition activities. The enzymes inhibition results showed the potential of synthesized compounds in controlling both type-II diabetes mellitus and Alzheimer's disease. In vitro biological investigations revealed that most of compounds were more active against yeast α-glucosidase than the reference compound acarbose (IC50 38.25±0.12µM). Among the tested series the compound 4c bearing 4-flouro benzyl group was noted to be the most active (IC50 25.6±0.2µM) against α-glucosidase, and it displayed weak inhibition activities against AChE and BChE. Compound 4a exhibited the most desired results against all three enzymes, as it was significantly active against all the three enzymes; α-glucosidase (IC50 32.2±0.3µM), AChE (IC50 50.2±0.8µM) and BChE (IC50 43.8±0.8µM). Due to the most favorable activity of 4a against the tested enzymes, for molecular modeling studies this compound was selected to investigate its pattern of interaction with α-glucosidase and AChE targets.

Synthesis, thymidine phosphorylase inhibition and molecular modeling studies of 1,3,4-oxadiazole-2-thione derivatives.

Thymidine phosphorylase (TP) inhibitors have attracted great attention due to their ability to suppress the tumors formation. In our ongoing research, a series of 1,3,4-oxadiazole-2-thione (1-12) has been synthesized under simple reaction conditions in good to excellent yields (86-98%) and their TP inhibition potential has also been evaluated. The majority of synthesized compounds showed moderate thymidine phosphorylase inhibitory activity with IC50 values ranging from 38.24±1.28 to 258.43±0.43µM, and 7-deazaxanthine (7DX) was used as a reference compound (IC50 38.68±4.42). The TP activity was very much dependent on the C-5 substituents; among this series the compound 6 bearing 4-hydroxyphenyl group was found to be the most active with IC50 38.24±1.28µM. Molecular docking studies revealed their binding mode.