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.

2-(3-Methyl-2-oxoquinoxalin-1-yl)-N-(4-methyl-phen-yl)acetamide.

The quinoxaline moiety in the title mol-ecule, C18H17N3O2, is not quite planar and the p-tolyl group is rotationally disordered over two nearly equally populated sets of sites. In the crystal, N-H⋯O and C-H⋯O hydro-gen bonds form chains extending along the b-axis direction. Due to the disorder of the p-tolyl rings, short C⋯C distances are observed between adjacent chains.

N-(4-Methoxy-2-nitrophenyl)-2-(3-methyl-2-oxo-1,2-dihydroquinoxalin-1-yl)acetamide.

The quinoxaline unit in the title mol-ecule, C18H16N4O5, is slightly puckered [dihedral angle between the rings = 2.07 (12)°] while the whole mol-ecule adopts an L-shaped conformation. Intra-molecular hydrogen bonding determines the orientation of the substituted phenyl ring and the amide nitro-gen atom is almost planar. The packing in the crystal is governed by C-H⋯O hydrogen bonds and slipped π-stacking inter-actions.

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.

Crystal structure of ethyl 2-{4-[(2-oxo-3-phenyl-1,2-di-hydro-quinoxalin-1-yl)meth-yl]-1H-1,2,3-triazol-1-yl}acetate.

The quinoxaline portion of the title mol-ecule, C21H19N5O3, is not quite planar as indicated by a dihedral angle of 3.38 (7)° between the constituent rings. The mol-ecule is 'U-shaped', which is consolidated by an intra-molecular anti-parallel carbonyl electrostatic inter-action with C··O distances of 2.8905 (16) and 3.0221 (15) Å, in the crystal forms corrugated layers through C-H⋯O and C-H⋯N hydrogen bonds and C-H⋯π(ring) and π-stacking inter-actions.

2-Azido-N-(4-methyl-phen-yl)acetamide.

The asymmetric unit of the title compound, C9H10N4O, comprises three independent mol-ecules, two pairs of which differ significantly in the rotational orientation of the azido group and one pair having very similar conformations; the N-N-C-C torsion angles are -173.9 (2), -102.7 (2) and -173.6 (2)°. In the crystal, each independent mol-ecule forms N-H⋯O hydrogen bonds with its glide-plane-related counterparts, forming zigzag chains extending along the c-axis direction.

Crystal structure and Hirshfeld surface analysis of 2-azido-N-(4-fluoro-phen-yl)acetamide.

The asymmetric unit of the title compound, C8H7FN4O, consists of two independent mol-ecules differing in the orientation of the azido group. Each mol-ecule forms N-H⋯O hydrogen-bonded chains along along the c-axis direction with its symmetry-related counterparts and the chains are connected by C-F⋯π(ring), C=O⋯π(ring) and slipped π-stacking inter-actions. A Hirshfeld surface analysis of these inter-actions was performed.

Crystal structure and Hirshfeld surface analysis of 2-chloro-N-(4-meth-oxy-phen-yl)acetamide.

In the title mol-ecule, C9H10ClNO2, the meth-oxy group lies very close to the plane of the phenyl ring while the acetamido group is twisted out of this plane by 28.87 (5)°. In the crystal, a three-dimensional structure is generated by N-H⋯O, C-H⋯O and C-H⋯Cl hydrogen bonds plus C-H⋯π(ring) inter-actions. A Hirshfeld surface analysis of the inter-molecular inter-actions was performed and indicated that C⋯H/H⋯C inter-actions make the largest contribution to the surface area (33.4%).

A possible potential COVID-19 drug candidate: Diethyl 2-(2-(2-(3-methyl-2-oxoquinoxalin-1(2H)-yl)acetyl)hydrazono)malonate: Docking of disordered independent molecules of a novel crystal structure, HSA/DFT/XRD and cytotoxicity.

This study reports the synthesis, characterization and importance of a novel diethyl 2-(2-(2-(3-methyl-2-oxoquinoxalin-1(2H)-yl)acetyl)hydrazono)malonate (MQOAHM). Two independent molecular structures of the disordered MQOAHM have been established by XRD­single­crystal analysis in a ratio of 0.596(3)/0.404(3), MQOAHM (a) and MQOAHM (b), respectively. MQOAHM was characterized by means of various spectroscopic tools ESI-MS, IR, 1H &13C NMR analyses. Density Functional Theory (DFT) method, B3LYP, 6-311++G(d,p) basis set was used to optimize MQOAHM molecule. The obtained theoretical structure and experimental structure were superimposed on each other, and the correlation between them was calculated. The Highest Occupied Molecular Orbital (HOMO) and Lowest Unoccupied Molecular Orbital (LUMO) were created, and the energy gap between these orbitals was calculated. For analyzing intermolecular interactions, Molecular Electrostatic Potential (MEP) and Hirshfeld Surface Analysis were studied. For a fair comparative study, the two forms of the title compound were docked together with 18 approved drugs and N3 under precisely the same conditions. The disordered molecule structure's binding scores against 7BQY were -7.0 and -6.9 kcal/mol-1 for MQOAHM (a) and MQOAHM (b), respectively. Both the forms show almost identical superimposed structures and scores indicating that the disorder of the molecule, in this study, has no obvious effect. The high binding score of the molecule was attributed to the multi-hydrogen bond and hydrophobic interactions between the ligand and the receptor's active amino acid residues. Worth pointing out here that the aim of using the free energy in Silico molecular docking approach is to rank the title molecule compared to the wide range of approved drugs and a well-established ligand N3. The binding scores of all the molecules used in this study are ranged from -9.9 to -4.5 kcal/mol-1. These results and the supporting statistical analyses suggest that this malonate-based ligand merits further research in the context of possible therapeutic agents for COVID-19. Cheap computational techniques, PASS, Way2drug and ADMET, online software tools, were used in this study to uncover the title compound's potential biological activities and cytotoxicity.