Wafaa A. Zaghary

First Synthesis of Thiophene Thioglycosides

A new method for the preparation of a new class of thiophene thioglycosides via one-pot reaction of the sodium thiophenethiolate salts with 2,3,4,6-tetra-O-acetyl-α-D-gluco- and galacto-pyranosyl bromides has been studied. The sodium thiophenethiolate salts are prepared using cyano-di-thioic analogs and their corresponding mono- and dithiolate salts.

New Trends in Synthesis of Pyrazole Nucleosides as New Antimetabolites

Pyrazole nucleosides and condensed pyrazole nucleosides exhibit various biological activities. This article describes recent synthetic approaches to their preparation, chemical properties, biological activities, and structure-activity relationships, with emphasis to selected drugs or drug candidates. Two pyrazole C-nucleoside compounds pyrazofurin (pyrazomycin) and its α-epimer pyrazofurin B are active components of potent antivirals approved for therapeutic use in human medicine aimed against various diseases caused by DNA viruses.

First Synthesis of Thienopyrazole Thioglycosides

Reported is the first method to prepare a new class of thienopyrazole thioglycosides via a one‐pot reaction of the sodium thienopyrazolthiolate salts with 2,3,4,6‐tetra‐O‐acetyl‐α‐D‐gluco‐and galactopyranosyl bromides. The sodium thienopyrazolthiolate salts are prepared using pyrazoldithioic acids and their corresponding mono ‐ and dithiolate salts.

A Direct Route to a New Class of Acrylamide Thioglycosides

The preparation of a new class of acrylamide thioglycosides via one‐pot reaction of the potassium 2‐cyanoethylene‐1‐thiolate salts with 2,3,4,6‐tetra‐O‐acetyl‐α‐D‐gluco‐ and galactopyranosyl bromides has been studied. The E‐configuration of these thioglycosides was proven by their transformations to the corresponding 5‐aminopyrazoles.

Synthesis, Molecular Docking and Preliminary in-Vitro Cytotoxic Evaluation of Some Substituted Tetrahydro- naphthalene (2',3',4',6'-Tetra-O-Acetyl-β-D-Gluco / - Galactopyranosyl) Derivatives

A facile, convenient and high yielding synthesis of novel S-glycosides and N-glycosides incorporating 1,2,3,4-tetrahydronaphthalene and or 1,2-dihydropyridines moieties has been described. The aglycons 2, 4, and 7 were coupled with different activated halosugars in the presence of basic and acidic medium. The preliminary in-vitro cytotoxic evaluation revealed that compounds 3c, 3f, 5c and 7b show promising activity. A molecular docking study was performed against tyrosine kinase (TK) (PDB code: 1t46) by Autodock Vina. The docking output was analyzed and some compounds have shown hydrogen bond (H-B) formation with reasonable distances ranged from 2.06 A° to 3.06 A° with Thr 670 and Cys 673 residues found in the specified pocket. No hydrogen bond was observed with either Glu 640 nor Asp 810 residues, as was expected from pdbsum.

S-glycosides in medicinal chemistry: Novel synthesis of cyanoethylene thioglycosides and their pyrazole derivatives

ABSTRACT A one-pot reaction of a sodium 2-cyanoethylene-1-thiolate salt with 2,3,4,6-tetra-O-acetyl-α-D-gluco- and galactopyranosyl bromides affords a new class of cyanoethylene thioglycosides. The conversion to the corresponding 5-aminopyrazoles confirms the E-configuration of these cyanoethylene thioglycosides.

Suitability of various chromatographic and spectroscopic techniques for analysis and kinetic degradation study of trelagliptin

Multifaceted comparative analytical methods for trelagliptin (TRL) were investigated, applied to ZAFATEK tablets and HPLC-UV was selected for a degradation kinetic study. UPLC-MS/MS (Method I), UPLC-UV (Method II), HPLC-UV (Method III), UHPLC-UV (Method IV) and direct UV (Method V) methods were developed. Methods (I-V) showed satisfactory results using TRL concentration ranges of 50–800 ng/mL, 2.5–80 μg/mL, 5–100 μg/mL, 5–100 μg/mL and 5–50 μg/mL, respectively. Multiple Reaction Monitoring (MRM) of the transition pairs of m/z 358.176 to 134.127 for TRL and m/z 340.18 to 116.08 for alogliptin (IS) were employed utilizing positive mode Electrospray Ionization (ESI). The degradation kinetic study (Method VI) was carried out using 1 N HCl based on three different temperatures (70 °C, 80 °C and 90 °C). Through the optimized method-3, a good chromatographic separation of TRL from its major degradation product was achieved. Arrhenius plot was used in the kinetic study and the apparent 1st order degradation rate constant (K), t1/2, t90, and the activation energies were calculated for each temperature and at 25 °C. The optimized UPLC-MS/MS method is suitable for further TRL assay either in biological fluids or in the presence of impurities.

Comparative study between different simple methods manipulating ratio spectra for the analysis of alogliptin and metformin co-formulated with highly different concentrations

Different simple spectrophotometric methods were developed for simultaneous determination of alogliptin and metformin manipulating their ratio spectra with successful application on recently approved combination, Kazano® tablets. Spiking was implemented to detect alogliptin in spite of its low contribution in the pharmaceutical formulation as low quantity in comparison to metformin. Linearity was acceptable over the concentration range of 2.5-25.0μg/mL and 2.5-15.0μg/mL for alogliptin and metformin, respectively using derivative ratio, ratio subtraction coupled with extended ratio subtraction and spectrum subtraction coupled with constant multiplication. The optimized methods were compared using one-way analysis of variance (ANOVA) and proved to be accurate for assay of the investigated drugs in their pharmaceutical dosage form.

Chapter Five – Salmeterol Xinafoate

Salmeterol xinafoate is a potent and a long-acting β2-adrenoceptor agonist. It is prescribed for the treatment of severe persistent asthma and chronic obstructive pulmonary disease. Different methods were used to prepare (R)-(-)-salmeterol such as: mixing a sample of 4-benzyloxy-3-hydroxymethyl-ω-bromoacetophenone with sodium lauryl sulfate and the mixture was added to the microbial culture of Rhodotorula rubra, treatment of p-hydroxyacetophenone with Eschenmosers salt and carbonate exchange resin followed by a sequence of supported reagents and scavenging agents or via Rh-catalyzed asymmetric transfer hydrogenation. The enantioselective synthesis of (S)-salmeterol was achieved via asymmetric reduction of the azidoketone 4 by Pichia angusta yeast. Physical characteristics of salmeterol xinafoate were confirmed via: X-ray powder diffraction pattern, thermal analysis and UV, vibrational, nuclear magnetic resonance, and mass spectroscopical data. Initial improvement in asthma control may occur within 30 min following oral inhalation of salmeterol in fixed combination with fluticasone propionate. Clinically important improvements are maintained for up to 12 h in most patients. It is extensively metabolized in the liver by hydroxylation, thus increased plasma concentrations may occur in patients with hepatic impairment.

Synthesis, characterization and evaluation of99mTc-L, L-ethylenecysteine dimer to assess regional cerebral blood flow

L,L-ethylenecysteine dimer (L,L-ECD) compound was synthesized with an overall yield 31.2% and a melting point 197–198°C. A systematic study has been carried out on the labelling of L,L-ECD with technetium-99m by ligand exchange via99mTc-EDTA. The percent labelling yield of L,L-ECD was found ≥95% when 0.75 2.0 mg and 100 μg of L,L-ECD, disodium-EDTA and tin (II) were used, respectively, at pH 5.5. The produced99mTc-L,L-ECD complex is stable, neutral and lipid soluble. The99mTc-L,L-ECD complex penetrate the blood-brain barrier following intravenous injection in the tail vein of mice with an initial brain uptake equal to 0.9% at 2 minutes and a slow washout equal to 0.65% after 25 minutes. High uptake in the gastrointestinal tract (GIT) was observed. It reaches up to 38.9% at 2 minutes and increased as time pass reaching 48.3% at 60 minutes. These results indicate that this ligand is suitable for brain imaging and has a tendency to be excreted via liver and GIT due to its lipophilicity.