Synthesis, characterization, X-ray, α-glucosidase inhibition and molecular docking study of new triazolic systems based on 1,5-benzodiazepine via 1,3-dipolar cycloaddition reactions.

We report in this work a synthesis of novel triazolo[1,5]benzodiazepine derivatives by the 1,3-dipolar cycloaddition reaction of N-aryl-C-ethoxycarbonylnitrilimines with 1,5-benzodiazepines. All the structures of the new compounds were determined from their NMR (1H and 13C) and HRMS. Then, X-ray crystallography analysis of compound 4d confirmed the stereochemistry of cycloadducts. The compounds 1, 4a-d, 5a-d, 6c, 7 and 8 were evaluated for their in vitro anti-diabetic activity against α-glucosidase. The compounds 1, 4d, 5a and 5b showed potential inhibitory activities compared to standard acarbose. Additionally, an in silico docking study was conducted to look into the active binding mode of the synthesized compounds within the target enzyme.Communicated by Ramaswamy H. Sarma.

Synthesis, structural characterizations, in vitro biological evaluation and computational investigations of pyrazole derivatives as potential antidiabetic and antioxidant agents.

In this study, a two pyrazole derivatives; 2-(5-methyl-1H-pyrazole-3-carbonyl)-N-phenylhydrazine-1-carboxamide (Pyz-1) and 4-amino-5-(5-methyl-1H-pyrazol-3-yl)-4H-1,2,4-triazole-3-thiol (Pyz-2) were synthesized and characterized by 13C-NMR, 1H-NMR, FT-IR, and mass spectrometry. A complete molecular structures optimization, electronic and thermodynamic properties of Pyz-1 and Pyz-2 in gas phase and aqueous solution were predicted by using hybrid B3LYP method with the 6-311++G** basis sets. Pyz-1 and Pyz-2 were evaluated in vitro for their anti-diabetic, antioxidant and xanthine oxidase inhibition activities. For anti-diabetic activity, Pyz-1 and Pyz-2 showed a potent α-glucosidase and α-amylase inhibition with IC50 values of 75.62 ± 0.56, 95.85 ± 0.92 and 119.3 ± 0.75, 120.2 ± 0.68 µM, respectively, compared to Acarbose (IC50(α-glucosidase) = 72.58 ± 0.68 µM, IC50(α-amylase) = 115.6 ± 0.574 µM). In xanthine oxidase assay, Pyz-1 and Pyz-2 exhibited remarkable inhibitory ability with IC50 values 24.32 ± 0.78 and 10.75 ± 0.54 µM, respectively. The result of antioxidant activities showed that the title compounds have considerable antioxidant and radical scavenger abilities. In addition, molecular docking simulation was used to determine the binding modes and energies between the title compounds and α-glucosidase and α-amylase enzymes.

Synthesis, structural characterization, antioxidant and antidiabetic activities, DFT calculation, and molecular docking of novel substituted phenolic and heterocyclic compounds.

The current work describes the preparation of three unexpected compounds: a tetrasubstituted phenolic compound, an isocoumarin, and a pyranopyridine, bearing various substituent groups obtained through the condensation of 6-methyl-4-hydroxypyran-2-one 1 with 2-aminopyridine 2 under mild conditions. Plausible mechanisms explaining the formation of these compounds have been presented. Their structures have been elucidated using spectral data and confirmed by crystallographic studies. Furthermore, optimized geometries of and electronic distribution of FMOs orbitals are investigated in the PCM solvent model at the B3LYP/6-311++G(d,p) level of theory. The compounds were tested for their antioxidant and antidiabetic activities. Moreover, the binding interactions between the compounds and α-glucosidase and α-amylase were determined through their docking into the binding sites of the target enzymes using the Autodock package.Communicated by Ramaswamy H. Sarma.

New styrylquinoxaline: synthesis, structural, biological evaluation, ADMET prediction and molecular docking investigations.

The organic compound (E)-3-(4-methylstyryl)quinoxalin-2(1H)-one (SQO) with molecular formula C17H14N2O was synthesized and analyzed using single crystal X-ray diffraction, 1H, 13C NMR and FTIR spectroscopic techniques. The geometric parameters of the molecule was optimized by density-functional theory (DFT) choosing B3LYP with 6-31++G(d,p) basis set. For compatibility, the theoretical structure and experimental structure were overlapped with each other. Frontier molecular orbitals of the title compound were made, and energy gap between HOMO and LUMO was calculated. Molecular electrostatic potential map was generated finding electrophilic and nucleophilic attack centers using DFT method. Hirshfeld surface analysis (HSA) confirms active regions at the circumference of N1 atoms and O1 atoms that form intermolecular N1-H1···O1 hydrogen bond. The acute oral toxicity study was carried out according to OECD guideline, which approve that the compound SQO was non-toxic. In addition, this quinoxaline derivative was evaluated for its in vitro antidiabetic activity against α-glucosidase and α-amylase enzymes and for antioxidant activity by utilizing several tests as 1,1-diphenyl-2-picryl hydrazyl, (2,2'-azino-bis(3-ethyl benzthiazoline-6-sulfonicacid), reducing power test (FRAP) and hydrogen peroxide activity H2O2. The molecular docking studies were performed to investigate the antidiabetic activity of SQO and compared with the experimental results. SQO is a potent antidiabetic from both the experimental and molecular docking results. Finally, the physicochemical, pharmacokinetic and toxicological properties of SQO have been evaluated by using in silico absorption, distribution, metabolism, excretion and toxicity analysis prediction.

Synthesis, design, in silico, in vitro and in vivo (streptozotocin-induced diabetes in mice) biological evaluation of novels N-arylacetamide derivatives.

The organic compounds 2-chloro-N-(aryl)acetamide (Ps13-Ps18) and 2-azido-N-(aryl)acetamide (148-153) were synthesized and analyzed using 1 H, 13C NMR. The acute oral toxicity study was carried out according to OECD guidelines, which approve that the compounds (Ps18 and 153) were nontoxic. In addition, the compounds were evaluated for its antidiabetic and antihyperglycemic properties (in vitro and in vivo) and for antioxidant activity by utilizing several tests as 1,1-diphenyl2-picrylhydrazyl DPPH, (2,2'-azino-bis(3-ethyl benzthiazoline-6-sulfonicacid) ABTS, reducing power test FRAP and hydrogen peroxide activity H2O2. The molecular docking studies were performed to investigate the antidiabetic activity of Ps18 and 153 and compared with the experimental results. These compounds are a potent antidiabetic from both the experimental and molecular docking results. Finally, the physicochemical, pharmacokinetic and toxicological properties of Ps18 and 153 have been evaluated by using in silico absorption, distribution, metabolism, excretion and toxicity analysis prediction.Communicated by Ramaswamy H. Sarma.

Acute and Subacute Toxicity Studies of Erodium guttatum Extracts by Oral Administration in Rodents.

The present study aimed to evaluate the acute and subacute toxicity profiles of Erodium guttatum extracts in mice using the methods described in the guidelines of the OECD. In the acute toxicity study, the LD50 value was greater than 2000 mg/kg. The subacute toxicity study of E. guttatum extracts showed no significant changes in body or organ weights. The administration of E. guttatum extracts to mice at a dose of 200 mg/kg led to an increase in white blood cells, platelets and hemoglobin. Moreover, the aqueous extract of E. guttatum only decreased liver aspartate aminotransferase (ASAT) levels at a dose of 200 mg/kg, and creatinine and urea levels did not show any significant alterations compared to the control group. Our results showed that the extracts of E. guttatum caused a slight increase in alanine aminotransferase (ALAT) and triglycerides. The histological study showed that mice treated with E. guttatum extracts experienced some histopathological changes in the liver, particularly with the methanolic extract, and slight changes in the kidneys and pancreas. Regarding the renal profile, no toxicity was observed. These results provide basic information on the toxicological profile of E. guttatum used in traditional medicine.