Synthesis, crystal structure and Hirshfeld surface analysis of 1-[(1-octyl-1H-1,2,3-triazol-4-yl)methyl]-3-phenyl-1,2-di-hydro-quinoxalin-2(1H)-one.

In the title mol-ecule, C25H29N5O, the di-hydro-quinoxaline unit is not quite planar (r.m.s. deviation = 0.030 Å) as there is a dihedral angle of 2.69 (3)° between the mean planes of the constituent rings and the mol-ecule adopts a hairpin conformation. In the crystal, the polar portions of the mol-ecules are associated through C-H⋯O and C-H⋯N hydrogen bonds and C-H⋯π(ring) and C=O⋯π(ring) inter-actions, forming thick layers parallel to the bc plane and with the n-octyl groups on the outside surfaces.

Synthesis, crystal structure and Hirshfeld surface of ethyl 2-[2-(methyl-sulfan-yl)-5-oxo-4,4-diphenyl-4,5-di-hydro-1H-imidazol-1-yl]acetate (thio-phenytoin derivative).

The di-hydro-imidazole ring in the title mol-ecule, C20H20N2O3S, is slightly distorted and the lone pair on the tri-coordinate nitro-gen atom is involved in intra-ring π bonding. The methyl-sulfanyl substituent lies nearly in the plane of the five-membered ring while the ester substituent is rotated well out of that plane. In the crystal, C-H⋯O hydrogen bonds form inversion dimers, which are connected along the a- and c-axis directions by additional C-H⋯O hydrogen bonds, forming layers parallel to the ac plane. The major contributors to the Hirshfeld surface are C⋯H/H⋯C, O⋯H/H⋯O and S⋯H/H⋯S contacts at 20.5%, 14.7% and 4.9%, respectively.

Synthesis, crystal structure and Hirshfeld surface analysis of 1-[3-(2-oxo-3-phenyl-1,2-di-hydro-quinoxalin-1-yl)prop-yl]-3-phenyl-1,2-di-hydro-quinoxalin-2-one.

In the title compound, C31H24N4O2, the di-hydro-quinoxaline units are both essentially planar with the dihedral angle between their mean planes being 64.82 (4)°. The attached phenyl rings differ significantly in their rotational orientations with respect to the di-hydro-quinoxaline planes. In the crystal, one set of C-H⋯O hydrogen bonds form chains along the b-axis direction, which are connected in pairs by a second set of C-H⋯O hydrogen bonds. Two sets of π-stacking inter-actions and C-H⋯π(ring) inter-actions join the double chains into the final three-dimensional structure.

Synthesis, crystal structure and Hirshfeld surface analysis of 2-[(4-hy-droxy-phen-yl)amino]-5,5-diphenyl-1H-imidazol-4(5H)-one.

In the title mol-ecule, C21H17N3O2, the five-membered ring is slightly ruffled and dihedral angles between the pendant six-membered rings and the central, five-membered ring vary between 50.78 (4) and 86.78 (10)°. The exocyclic nitro-gen lone pair is involved in conjugated π bonding to the five-membered ring. In the crystal, a layered structure is generated by O-H⋯N and N-H⋯O hydrogen bonds plus C-H⋯π(ring) and weak π-stacking inter-actions.

Synthesis, crystal structure and Hirshfeld surface analysis of 2-phenyl-3-(prop-2-yn-1-yl-oxy)quin-oxaline.

In the title compound, C17H12N2O, the quinoxaline moiety shows deviations of 0.0288 (7) to -0.0370 (7) Šfrom the mean plane (r.m.s. deviation of fitted atoms = 0.0223 Å). In the crystal, corrugated layers two mol-ecules thick are formed by C-H⋯N hydrogen bonds and π-stacking inter-actions.

Crystal structure and Hirshfeld surface analysis of 3-phenyl-1-{3-[(3-phenyl-quinoxalin-2-yl)-oxy]prop-yl}-1,2-di-hydro-quinoxalin-2-one.

In the title compound, C31H24N4O2, the quinoxaline units are distinctly non-planar and twisted end-to-end. In the crystal, C-H⋯O and C-H⋯N hydrogen bonds link the mol-ecules into chains extending along the a-axis direction. The chains are linked through π-stacking inter-actions between inversion-related quinoxaline moieties.

Synthesis, crystal structure, DFT, Hirshfeld surface analysis, energy frameworks and in-Silico drug-targeting PFKFB3 kinase of novel triazolequinoxalin derivative (TZQ) as a therapeutic Strategy against cancer.

Overall, drug design is a dynamic and evolving field, with researchers constantly working to improve their understanding of molecular interactions, develop new computational methods, and explore innovative techniques for creating effective and safe medications. The process can involve steps such as the identification of targets, the discovery of lead compounds, lead optimization, preliminary testing, human trials, regulatory approval and finally post-marketing surveillance, all aimed at bringing a new drug from concept to market. In this article, the synthesis of the novel triazolequinoxalin (TZQ) 1-((1-hexyl-1H-1,2,3-triazol-5-yl)methyl)-3-phenylquinoxalin-2(1H)-one (4) is reported. The structure has been identified with a variety of spectroscopic methods (1H, 13C NMR, and LC-MS) and finally, the structure has been determined by X-ray diffraction (XRD) studies. The TZQ molecule has crystallized in the monoclinic space C2/c group with unit cell dimensions a = 41.201(2) Å, b = 10.6339(6) Å, c = 9.4997(4) Å, ß = 93.904(4). The crystal structure is stabilized by intermolecular interactions (N-H ⋯ O and N-H … Cg) occurring within the molecule. The presence of these intermolecular interactions is evaluated through analysis of Hirshfeld surfaces (HS) and two-dimensional (2D) chemical fingerprints map. Additionally, energy frameworks were employed to identify the prevailing interaction energy influencing the molecular arrangement. Density Functional Theory (DFT) calculations were computed to establish concurrence between theoretical and experimental results. Furthermore, the HOMO-LUMO energy levels were determined using the B3LYP/6-31+G(d, p) level of theory. Finally, molecular docking was used to predict the anti-cancer activity of the compound (4) against PFKFB3 kinase and presented noticeable hydrophilic and hydrophobic interactions at the active site region.

2-[4-(2-Chloro-benz-yl)-3-methyl-6-oxo-1,6-di-hydro-pyridazin-1-yl]-N-(4-fluoro-phen-yl)acetamide.

The conformation of the title mol-ecule, C20H17ClFN3O2, is partly determined by an intra-molecular C-H⋯O hydrogen bond, which leads to a dihedral angle of 14.7 (4)° between the fluoro-benzene ring and the acetamide group. The 2-chloro-benzyl group is rotationally disordered over two orientations in a 0.656 (2): 0.344 (2) ratio. In the crystal, a layered structure is formed by N-H⋯O, C-H⋯O and C-H⋯F hydrogen bonds plus slipped π-π stacking inter-actions.

Novel Pyrazole-Based Benzofuran Derivatives as Anticancer Agents: Synthesis, Biological Evaluation, and Molecular Docking Investigations.

In this work, the design, synthesis, and mechanistic studies of novel pyrazole-based benzofuran derivatives 1-8 as anticancer agents were discussed. Cytotoxic potency of the title compounds was evaluated against the lung carcinoma A-549, human-derived colorectal adenocarcinoma HT-29, breast adenocarcinoma MCF-7 cells as well as mouse fibroblast 3T3-L1 cells using XTT assay. Anticancer mechanistic studies were carried out with flow cytometry. XTT results revealed that all compounds exhibited dose-dependent anti-proliferative activity against the tested cancer cells, and especially compound 2 showed the strongest anti-proliferative activity with an IC50 value of 7.31 µM and the highest selectivity (15.74) on MCF-7 cells. Flow cytometry results confirmed that the cytotoxic power of compound 2 on MCF-7 cells is closely related to mitochondrial membrane damage, caspase activation, and apoptosis orientation. Finally, molecular docking studies were applied to determine the interactions between compound 2 and caspase-3 via in-silico approaches. By molecular docking studies, free binding energy (ΔGBind), docking score, Glide score values as well as amino acid residues in the active binding site were determined. Consequently, these results constitute preliminary data for in vivo anticancer studies and have the potential as a chemotherapeutic agent.

Diethyl 2,2'-[({2-chloro-5-[(2-eth-oxy-2-oxoeth-yl)(2-methyl-indolin-1-yl)carbamo-yl]phen-yl}sulfon-yl)aza-nedi-yl]di-acetate.

The majority of the title mol-ecule, C28H34ClN3O9S, is disordered over two closely spaced sets of sites; the site occupancy of the major component = 0.542 (3). The conformation of each component is approximately U-shaped with the chloro-benzene ring forming the base and the indolinyl and sulfamoyl groups the sides; an intra-molecular C-H⋯Cl hydrogen bond possibly contributes to the stabilization of the conformation. In the crystal, a corrugated layer structure parallel to the ab plane is formed by C-H⋯O and C-H⋯Cl hydrogen bonds together with C-H⋯π(ring) inter-actions.

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.

5,6,7,8-Tetra-hydro-[1,2,4]triazolo[5,1-b]quinazolin-9(4H)-one.

The triazole ring in the title mol-ecule, C9H10N4O, is not quite coplanar with the six-membered ring to which it is fused, the dihedral angle between the two least-squares planes being 2.52 (6)°. In the crystal, a layered structure is formed by N-H⋯N and C-H⋯O hydrogen bonds plus slipped π-stacking inter-actions, with the fused cyclo-hexene rings projecting to either side.

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.

3-Methyl-2-(methyl-sulfan-yl)-5,5-diphenyl-3,5-di-hydro-4H-imidazol-4-one.

In the title mol-ecule, C17H16N2OS, the di-hydro-imidazolone ring is slightly puckered and the methyl-sulfanyl group is nearly coplanar with it. In the crystal, two sets of C-H⋯O hydrogen bonds form corrugated layers of mol-ecules parallel to the ac plane. The layers pack with normal van der Waals contacts between them.

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.

15,15-Diphenyl-2,3,4,5,6,8,9,11,12-octa-hydro-imidazo[2,1-h][1,4,12]trioxa[7]thia-[9]azacyclo-tetra-decin-14(15H)-one.

The title mol-ecule, C23H26N2O4S, adopts a cup-shaped conformation. In the crystal, layers lying parallel to the ab plane are formed by C-H⋯O hydrogen bonds and C-H⋯π(ring) inter-actions. The layers stack along the c-axis direction through normal van der Waals inter-actions.

3-(2-Bromo-eth-yl)-5,5-di-phenyl-imidazolidine-2,4-dione.

The imidazolidine ring in the title mol-ecule, C17H15BrN2O2, is slightly ruffled [r.m.s. deviation = 0.0192 Å], while the attached phenyl rings at the C atom at the position between the amine and carbonyl centres are rotated well out of its mean plane [dihedral angles with the imidazolidine ring = 63.60 (8) and 76.4 (1)°]. In the crystal, a three-dimensional network features N-H⋯O and C-H⋯O hydrogen bonds together with C-H⋯π(ring) 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.

Synthesis, molecular docking, ADMET evaluation and in vitro cytotoxic activity evaluation on RD and L20B cell lines of 3-substituted 5,5-diphenylimidazolidine-2,4-dione derivatives.

Hydantoins comprise an important class of compounds which have long attracted attention due to their remarkable biological and pharmacological properties including antitumor and antiviral activities. As a continuation of our studies on hydantoins derivatives we report the successful synthesis of hydantoins derivatives. These synthesized compounds were evaluated for their cytotoxic activity against Vero cells L20B (African green monkey kidney cell line) and Human Rhabdomyosarcoma RD cell lines using methotrexate drug (MTX) as a reference drug in cytotoxic activity studies. The percentage of the cell line viability was carried out by using Trypan blue dye exclusion method. The tested compounds showed equipotent cytotoxicity effect against Vero cells (L20B) and a moderate effect against Human Rhabdomyosarcoma (RD) cell lines. These results exhibited better activity for 4a-b compounds than the reference drug methotrexate (MTX). Molecular docking studies indicated that the synthesized compounds are suitable inhibitors of humain dihydrofolate reductase (DHFR) enzyme, which may explain the high antiproliferative activity.Communicated by Ramaswamy H. Sarma.

[Cu(dipicolinoylamide)(NO3)(H2O)] as anti-COVID-19 and antibacterial drug candidate: Design, synthesis, crystal structure, DFT and molecular docking.

For first time the new N-picolinoypicolinlamide was obtained as in situ ligand during the reaction of 2,4,6-ris(2-pyridyl)-,3,5-triazine with aqueous solution of CuNO3·3H2O and formed the corresponding complex [Cu(dipicolinoylamide)(NO3)(H2O)]. The crystal structure of the obtained complex was determined by x-ray structure. The complex crystallizes in space group P21/n, a = 10.2782(9) Å, b = 7.5173(6) Å, c = 17.738(2) Å, α = 90.00°, ß = 91.368(1)°, γ = 90.00°, V = 1370.1(2) Å3, Z = 4. The copper center has a distorted octahedral geometry. DFT calculations show good agreement between theoretical and X-ray data. The Molecular docking studies were executed to consider the nature of binding and binding affinity of the synthesized compounds with the receptor of COVID-19 main protease viral protein (PDB ID: 6lu7), the receptor of gram -ve bacteria (Escherichia coli, PDB ID: 1fj4) and the receptor of gram +ve bacteria (Staphylococcus aureus, PDB ID: 3q8u and Proteus PDB ID: 5i39) and with human DNA. Finally, in silico ADMET predictions was also examined.