Synthesis, and evaluation of α-amylase and α-glucosidase inhibitory potential of new pyrazolo[3,4-d]pyrimidine derivatives

A series of new pyrazolo[3,4-d]pyrimidine compounds were synthesized in excellent yields via sulfuration and 1,3-dipolar cycloaddition and confirmed by MS, FT-IR and NMR techniques. All the prepared compounds were screened in vitro for their α-amylase and α-glucosidase inhibitory activities. Preliminary results indicated that some target compounds exhibited promising α-amylase and α-glucosidase inhibitory activity potency. Among the tested products, the cycloadduct f was found most active inhibitor (IC50 = 134.30 μM) for α-amylase, and the sulphur product b is the most active inhibitor (IC50 = 16.37 μM) for α-glucosidase

La chimie thérapeutique des Antituberculeux

Le but de cette mise au point est d’établir une approche thérapeutique dans la prise en charge de la tuberculose. La plupart des patients atteints de tuberculose suivront l’un des schémas thérapeutiques antituberculeux standard recommandés par l’OMS selon la catégorie de malade. Tous ces schémas sont composés d’une association de quatre médicaments essentiels appelés « antituberculeux du premier intention » : isoniazide, rifampicine, pyrazinamide et éthambutol. Les antituberculeux mineurs ou de relais dits «de seconde intention » qui servent de traitement d’appoint : aminosides (streptomycine, amikacine et capréomycine), fluoroquinolones (ofloxacine, ciprofloxacine, moxifl oxacine et lévofloxacine), rifabutine, acide para- aminosalicylique, D- cyclosérine, éthionamide, sont utilisés après échec des dérivés de première ligne et sont considérés comme moins efficaces et/ou plus toxiques. En dehors des médicaments disponibles, la thérapeutique constitue toujours un handicap en matière de lutte antituberculeus

Ethyl 2-(4-benzyl-3-methyl-6-oxo-1,6-dihydropyridazin-1-yl)acetate: crystal structure and Hirshfeld surface analysis

The title compound, C16H18N2O3, is constructed about a central oxopyridazinyl ring (r.m.s. deviation = 0.0047 A˚ ), which is connected to an ethylacetate group at the N atom closest to the carbonyl group, and benzyl and methyl groups second furthest and furthest from the carbonyl group, respectively. An approximately orthogonal relationship exists between the oxopyridazinyl ring and the best plane through the ethylacetate group [dihedral angle = 77.48 (3)]; the latter lies to one side of the central plane [the Nr—Nr—Cm—Cc (r = ring, m = methylene, c = carbonyl) torsion angle being 104.34 (9)]. In the crystal, both H atoms of the N-bound methylene group form methylene-C—HO(ring carbonyl) or N(pyridazinyl) interactions, resulting in the formation of a supramolecular tape along the a-axis direction. The tapes are assembled into a three-dimensional architecture by methyl- and phenyl-C—HO(ring carbonyl) and phenyl-C— HO(ester carbonyl) interactions. The analysis of the calculated Hirshfeld surface indicates the dominance of HH contacts to the overall surface (i.e. 52.2%). Reflecting other identified points of contact between molecules noted above, OH/HO (23.3%), CH/HC (14.7%) and NH/HN (6.6%) contacts also make significant contributions to the surface

Synthesis, structural characterisation and theoretical studies of a novel pyridazine derivative: Investigations of anti-inflammatory activity and inhibition of α-glucosidase

X-ray crystallography on pyridazine 1 (ethyl 2-(3-methyl-4-(4-methylbenzyl)-6-oxopyridazin1(6H)-yl)acetate) shows the planar pyridazinyl ring to exhibit significant delocalisation of πelectron density over the constituent atoms and to be substituted with oxo, methyl, (4- methylphenyl)methyl and N-bound ethylacetate groups. While three of the ring-bound atoms are close to co-planar with the ring, the ethylacetate group is not; the latter exhibits a definitive kink in its conformation. In the molecular packing of 1, helical supramolecular chains along the b-axis are formed through O- and N-methylene-C–H…O(carbonyl) and Omethylene-C–H…π(pyridazinyl) interactions. The chains are connected into a supramolecular layer by π(pyridazinyl)…π(phenyl) interactions. The flat layers stacks along the c-axis 2 without directional interactions between them. The geometry-optimisation of 1 resulted in the straightening of terminal ethylacetate group but no other substantial changes. Computational chemistry shows the most stabilising interactions in the crystal are due to the π(pyridazinyl)…π(phenyl) (-10.7 kcal/mol) followed by O- and N-methylene-C–H…O(carbonyl) (-9.5 and -9.0 kcal/mol, respectively). The most prominent identified interlayer interaction is a weak methylene-C–H···N(pyridazinyl) contact. Throughout, comparisons are made with the phenyl analogue of 1, namely 2. Most notably, the lattice energy of 1 is approximately 4.1 kcal/mol more stable than that of 2, an observation related to the influence upon the molecular packing exerted by the methyl substituent of 1. Compound 1 exhibits moderate inhibition against α-glucosidase, compared to Acarbose, and weak heatinduced haemolysis inhibition

(Z)-3-(4-Methylbenzylidene)-4-oxopentanoic acid

The title compound, C13H14O3, a levulinic acid derivative, crystallizes with two independent molecules (A and B) in the asymmetric unit. The compound adopts a Z configuration about the C=C bonds in both molecules. The dihedral angle between the toluene ring and the carboxylic acid group is 72.83 (7)° in molecule A and 83.64 (8)° in molecule B. The toluene rings are inclined to the ketone substituents by 27.03 (9)° for A and 30.84 (6)° for B. In the crystal, like molecules are linked by pairs of O—H...O hydrogen bonds, forming A–A and B-B inversion dimers

Synthesis, X-ray, spectroscopy, molecular docking and DFT calculations of (E)-N'-(2,4-dichlorobenzylidene)-5-phenyl-1H-pyrazole-3-carbohydrazide

(E)-N'-(2,4-dichlorobenzylidene)-5-phenyl-1H-pyrazole-3-carbohydrazide (E-DPPC) has been synthesized and characterized by FT-IR, 1H-NMR, ESI-MS, and single-crystal X-ray diffraction. The structures and properties of this new pyrazole-3-carbohydrazide derivative were studied in gas phase and aqueous solution by using Functional hybrid B3LYP/6-311++G** calculations in gas phase and in aqueous solution to study. Two stable structures (C1 and C2) with similar energies were found in the PES. C2 evidence a higher dipole moment and a volume contraction in solution attributed to the presence of donors and acceptors H bonds. Besides, the changes in orientation and direction of dipole moment vector in solution are attributed to the hydration of E-DPPC with water molecules. The repulsion existent between the negative MK, Mulliken and NPA charges on the N12 and O15 atoms explain the diminishing of N12-C14-O15 angle from 123.77 ° in gas phase to 123.03 ° in solution. Nucleophilic sites are visibly observed on the acceptor H bonds groups (N10, O15 and N22 atoms) while on the N18-H21, N12-H13, C11-H23, C2-H3, C17-H20 bonds characteristics electrophilic sites were found, being the N18-H21 bond the most labile donor of H bond with the lowest MEP and bond order values. NBO calculations suggest that C2 is clearly most stable in solution than in gas phase. AIM studies show that C2 is stable in both media due to new H bonds formed. Harmonic force fields in both media were calculated together with the scaled force constants while the 102 vibration normal modes expected for C2 were completely assigned. The comparisons of experimental NMR and UV-visible spectra with the corresponding predicted evidence reasonable correlations. Docking results also displayed that E-DPPC possessed good binding profile against receptor molecule and interacted with core residues of target protein

Synthesis, structural, molecular docking and spectroscopic studies of (E)-N'-(4-methoxybenzylidene)-5-methyl-1H-pyrazole-3-carbohydrazide

(E)-N'-4-methoxybenzylidene-5-methyl-1H-pyrazole-3-carbohydrazide (E-MBPC) has been synthesized and characterized by FT-IR, 1H & 13C NMR and ESI-MS spectroscopic methods. The (E)-configuration of hydrazonoic group was confirmed by single-crystal X-ray diffraction. Theoretical structures of E-MBPC in both gas phase and aqueous solution have been optimized by using hybrid B3LYP/6-311++G** calculations. Calculations in solution have shown that dipole moment increases from 7.97 D in the gas phase to 13.68 D in solution with solvation energy of −131.34 kJ/mol. Atomic charges have evidenced that the protonation of E-MBPC in solution could occur only in the N28 atom because those charges on this atom show negative values. Mapped MEP surfaces show that the nucleophilic sites is located on the O21 and N28 atoms including the N16 atom while the electrophilic sites are observed on the N24-H27 and N18-H19 bonds. NBO calculations support the high stability of E-MBPC in solution while frontier orbitals studies suggest low reactivity of E-MBPC in both media, as compared with the (E)-N'-(4-(dimethylamino)benzylidene)-5-methyl-1H-pyrazole-3-carbohydrazide derivative. The vibrational assignments of 93 vibration modes expected for E-MBPC were reported together with the corresponding force fields and force constants in both media. The predicted Raman and Ultraviolet-visible spectra were also reported for E-MBPC at the same level of theory. Good correlations were obtained between the predicted 1H- and 13C NMR spectra and the corresponding experimental ones. In addition, molecular docking studies between the title ligand and 4AMJ protein were performed. Docking results revealed that the title compound can be designed as a potential anti-diabetic agent

Synthesis and investigations of reactive properties, photophysical properties and biological activities of a pyrazole-triazole hybrid molecule

© 2022In this work, we report the synthesis, spectroscopic characterization, reactivity study, photophysical properties and evaluation of α-glucosidase inhibitory activity pyrazole-triazole hybrid molecule. Reactive properties of the title compound have been investigated using density functional theory (DFT) calculations. Local reactive descriptors such as condensed versions of Fukui functions and Molecular electrostatic potential were used to predict the chemical reactivity. Further, the influence of solvents on the photophysical properties was investigated by using Time independent Density Functional Theory (TDDFT) calculations. In addition, the in vitro anti-diabetic activity against α-glucosidase enzyme revealed that the title compound has α-glucosidase inhibitory activity with IC50 value of 43.92 µg/mL. Molecular docking studies were carried out to understand the binding mechanism of the title compound in the active site of the α-glucosidase enzyme. The stability of the protein-ligand complex was validated by Molecular Dynamics (MD) simulations and Molecular Mechanics Poisson-Boltzmann Surface Area (MMPBSA) analysis

Synthesis, crystal structure, DFT, α-glucosidase and α-amylase inhibition and molecular docking studies of (E)-N'-(4-chlorobenzylidene)-5-phenyl-1H-pyrazole-3-carbohydrazide

In this work, a novel crystal i.e. (E)-N'-(4-chlorobenzylidene)-5-phenyl-1H-pyrazole-3-carbohydrazide has been synthesized and characterized using various spectroscopic techniques. The (E)-configuration of the azomethine (Ndouble bondCH) was confirmed by single crystal X-ray analysis. The molecule crystallizes in the monoclinic space group, P21/c, a = 15.629(9) Å, b = 7.152(4) Å, c = 14.707(9) Å, β = 111.061(15)°, V = 1534.1(6) Å3 and Z = 4. In addition, the elucidated molecular structure was confirmed by comparing the predicted Z-matrix geometries and spectroscopic data with the experimental ones. DFT calculations have been carried out in gas and IEFPCM solvent at the B3LYP/6–31+G(d,p). The in vitro anti-diabetic potential of the title compound was evaluated against α-glucosidase and α-amylase enzymes. Molecular docking studies showed that the various interactions tightly anchored the title compound to the active site, which makes it a more potent α-glucosidase inhibitor compared to well-known Acarbose