Adel A. Marzouk

Synthesis and anti-inflammatory activity of some pyrazole derivatives

A novel series of pyrazoles containing benzenesulfonamides, 1,3,4-oxadiazole-2-thiones, 4-substituted-1,2,4-triazole-3-thiones, and 2-substituted-1,3,4-thiadiazoles has been synthesized. Anti-inflammatory activity of some synthesized compounds was evaluated in vivo utilizing a standard acute carrageenan-induced paw edema method. The most active anti-inflammatory agents 3, 8f, and 10f were evaluated for ulcerogenic liability in rats compared to indomethacin and celecoxib as reference standards. Molecular modeling studies were initiated herein to validate the attained pharmacological data and provide understandable evidence for the observed anti-inflammatory behavior.

4-(1-Allyl-4,5-diphenyl-1H-imidazol-2-yl)-N,N-dimethyl­aniline

The title compound, C26H25N3, crystallizes with four independent molecules, 1–4, in the asymmetric unit of the triclinic unit cell. The allyl substituents on the imidazole rings adopt similar conformations in all four molecules. The imadazole and the 4-and 5-substituted phenyl rings of two pairs of molecules in the asymmetric unit stack parallel to (110). In contrast, the dimethylaniline systems in these pairs of molecules are almost normal to one another, with dihedral angles of 85.84 (10) and 85.65 (10)° between the benzene rings of the two dimethylaniline fragments of molecules 1 and 2, and 3 and 4, respectively. The crystal structure features an extensive series of C—H⋯π interactions that link the molecules into undulating rows along the c axis. The crystal studied was a pseudo-merohedral twin with twin law [-100, 0-10, 111] and the BASF parameter refined to 0.513 (3).

A facile synthesis of 3D NiFe2O4 nanospheres anchored on a novel ionic liquid modified reduced graphene oxide for electrochemical sensing of ledipasvir: Application to human pharmacokinetic study

Novel and sensitive electrochemical sensor was fabricated for the assay of anti-HCV ledipasvir (LEDV) in different matrices. The designed sensor was based on 3D spinel ferromagnetic NiFe2O4 nanospheres and reduced graphene oxide (RGO) supported by morpholinium acid sulphate (MHS), as an ionic liquid (RGO/NSNiFe2O4/MHS). This sensor design was assigned to synergistically tailor the unique properties of nanostructured ferrites, RGO, and ionic liquid to maximize the sensor response. Electrode modification prevented aggregation of NiFe2O4, increasing electroactive surface area and allowed remarkable electro-catalytic oxidation of LEDV with an enhanced oxidation response. Differential pulse voltammetry was used for detection LEDV in complex matrices whereas; cyclic voltammetry and other techniques were employed to characterize the developed sensor properties. All experimental factors regarding sensor fabrication and chemical sensing properties were carefully studied and optimized. Under the optimum conditions, the designated sensor displayed a wide linear range (0.4-350 ng mL-1) with LOD of 0.133 ng mL-1. Additionally, the proposed sensor demonstrated good selectivity, stability and reproducibility, enabling the quantitative detection of LEDV in Harvoni® tablets, human plasma and in a pharmacokinetic study. Our findings suggest that the developed sensor is a potential prototype material for fabrication of high-performance electrochemical sensors.

2-(2,6-Di­chloro­phen­yl)-1-pentyl-4,5-diphenyl-1H-imidazole

The title compound, C26H24Cl2N2, crystallizes with two independent molecules (1 and 2) in the asymmetric unit. In molecule 1, the two phenyl and 2,6-dichlorophenyl rings are inclined to the imidazole ring at angles of 74.12 (14), 26.13 (14) and 67.30 (14)°, respectively. In molecule 2, due to the different molecular environment in the crystal, the corresponding angles are different, viz. 71.72 (15), 16.14 (15) and 80.41 (15)°, respectively. In the crystal, molecules 1 and 2 are linked by C—H⋯Cl interactions, and inversion-related 2 molecules are linked by C—H⋯π interactions. There are no other significant intermolecular interactions present.

2-[2-(4-Meth­oxy­phen­yl)-4,5-diphenyl-1H-imidazol-1-yl]ethanol

In the title compound, C24H22N2O2, the central imidazole ring makes dihedral angles of 49.45 (8), 88.94 (9) and 19.43 (8)° with the benzene ring and the two phenyl rings, respectively. The dihedral angle between the phenyl rings is 77.86 (9)°, and they form dihedral angles of 49.06 (9) and 67.31 (8)° with the benzene ring. In the crystal, molecules are linked by O—H⋯N hydrogen bonds, forming chains along the b axis. These chains are connected by C—H⋯O hydrogen bonds, forming a two-dimensional network parallel to (100). In addition, C—H⋯π interactions are also observed. The terminal C and O atoms of the ethanol group are disordered over two sets of sites with an occupancy ratio of 0.801 (5):0.199 (5).

Enhanced dispersive solid phase extraction assisted by cloud point strategy prior to fluorometric determination of anti-hepatitis C drug velpatasvir in pharmaceutical tablets and body fluids

An innovative spectrofluorometric method was developed for the analysis of a recently FDA approved anti-hepatitis C velpatasvir (VELP). The developed method was relied on dispersive solid phase extraction (dSPE) using synergistic effect of reduced graphene oxide (RGO) and cobalt hydroxide nanoparticles (CHNPs) in addition to cloud point extraction (CPE) using polyethylene glycol 6000 (PEG 6000) as non-ionic surfactant. This method combines the merits of preconcentration and interferences elimination achieved by dSPE and CPE, respectively. All relevant parameters such as surfactant concentration, ionic strength, pH, incubation time and others were thoroughly investigated and optimized. Fluorometric detection of VELP was carried out at excitation wavelength of 350 nm and emission wavelength of 415 nm. Under the optimum conditions, a linear calibration curve was achieved in the range of 0.5–45 ng mL−1. Limits of detection (LOD) and quantification (LOQ) based on three and ten times the standard deviation of the blank were 0.040 and 0.112 ng mL−1, respectively. This method was successfully applied for determination of VELP in real samples such as tablets, human plasma and urine samples with good recoveries.

2-(4-Meth-oxy-phen-yl)-1-pentyl-4,5-di-phenyl-1H-imidazole.

The title compound, C27H28N2O, is a lophine (2,4,5-triphenyl-1H-imidazole) derivative with an n-pentyl chain on the amine N atom and a 4-methoxy substituent on the benzene ring. The two phenyl and methoxybenzene rings are inclined to the imidazole ring at angles of 25.32 (7), 76.79 (5) and 35.42 (7)°, respectively, while the methoxy substituent lies close to the plane of its benzene ring, with a maximum deviation of 0.126 (3) Å for the methoxy C atom. In the crystal, inversion dimers linked by pairs of C—H⋯O hydrogen bonds generate R 2 2(22) loops. These dimers are stacked along the a-axis direction.

2-(4-Chloro­phen­yl)-4,5-diphenyl-1-(prop-2-en-1-yl)-1H-imidazole

The title compound, C24H19ClN2, crystallizes with two independent molecules in the asymmetric unit. The prop-2-enyl substituents on the imidazole rings adopt similar conformations in the two molecules. The 4-and 5-substituted phenyl rings and the benzene ring make dihedral angles of 67.06 (8), 5.61 (8) and 41.09 (8)°, respectively, with the imadazole ring in one molecule and 71.53 (8), 28.85 (8) and 41.87 (8)°, respectively, in the other. The crystal structure features C—H⋯π interactions and weak π–π stacking interactions [centroid–centroid distances = 3.6937 (10) and 4.0232 (10) Å] between the chlorophenyl rings, which form a three-dimensional supramolecular structure.

Morpholinium hydrogen sulfate (MHS) ionic liquid as an efficient catalyst for the synthesis of bio-active multi-substituted imidazoles (MSI) under solvent-free conditions

Abstract Morpholinium hydrogen sulfate as an ionic liquid was employed as a catalyst for the synthesis of a biologically active series of multi-substituted imidazoles by a four-component reaction involving the combination of benzil with different aromatic aldehydes, ammonium acetate, and 1-amino-2-propanol under solvent-free conditions. The key advantages of this method are shorter reaction times, very high yield, and ease of processing. Furthermore, the resulting products can be purified by a non-chromatographic method and the ionic liquid catalyst is reusable. All of these novel compounds have been fully characterized from spectral data. The X-ray crystal structures of two representative molecules are also detailed.

Crystal structure of 1-[2-(2,6-di-chloro-phen-yl)-4,5-diphenyl-1H-imidazol-1-yl]propan-2-ol.

The central imidazole ring of the title compound, C24H20Cl2N2O, is twisted with respect to with the planes of the 2,6-dichlorobenzene and two phenyl rings, making dihedral angles of 74.06 (18), 28.52 (17) and 67.65 (18)°, respectively. The phenyl ring not adjacent to the N-bonded 2-hydroxypropyl group shows the greatest twist, presumably to minimize steric interactions. In the crystal, molecules are linked by O—H⋯N and C—H⋯O hydrogen-bond contacts into chains along the a-axis direction. The series of parallel chains form a two-dimensional sheet approximately parallel to the bc diagonal. In addition, C—H⋯π interactions are observed between the sheets. The atoms of the 2-hydroxypropyl group and the N atom of the 1H-imidazole ring to which it is bonded are disordered over two sets of sites, with an occupancy ratio of 0.722 (5):0.278 (5). The structure was refined as an inversion twin.