Exploring the Effect of Bioisosteric Replacement of Carboxamide by a Sulfonamide Moiety on N‐Glycosidic Torsions and Molecular Assembly: Synthesis and X‐ray Crystallographic Investigation of N‐(β‐D‐Glycosyl)sulfonamides as N‐Glycoprotein Linkage Region Analogues

N‐Glycoprotein linkage region constituents, 2‐acetamido‐2‐deoxy‐β‐D ‐glucopyranose (GlcNAc) and asparagine (Asn) are conserved among all the eukaryotes. To gain a better understanding for nature’s choice of GlcNAcβAsn as linkage region constituents and inter‐ and intramolecular carbohydrate–protein interactions, a detailed systemic structural study of the linkage region conformation is essential. Earlier crystallographic studies of several N‐(β‐glycopyranosyl)alkanamides showed that N‐glycosidic torsion, ?_N, is influenced to a larger extent by structural variation in the sugar part than that of the aglycon moiety. To explore the effect of the bioisosteric replacement of a carboxamide group by a sulfonamide moiety on the N‐glycosidic torsions as well as on molecular assembly, several glycosyl methanesulfonamides and glycosyl chloromethanesulfonamides were synthesized as analogues of the N‐glycoprotein linkage region, and crystal structures of seven of these compounds have been solved. A comparative analysis of this series of crystal structures as well as with those of the corresponding alkanamido derivatives revealed that N‐glycosidic torsion, ?_N, does not alter significantly. Methanesulfonamido and chloromethanesulfonamido derivatives of GlcNAc display a different aglycon conformation compared to other sulfonamido analogues. This may be due to the cumulative effect of the direct hydrogen bonding between N1 and O1′ and C? H???O interactions of the aglycon chain, revealing the uniqueness of the GlcNAc as the linkage sugar.     

Unsteady natural convective flow past a moving vertical cylinder with heat and mass transfer

Transient natural convection boundary layer flow of an incompressible viscous fluid past an impulsively moving semi- infinite vertical cylinder is considered. The temperature and concentration of the cylinder surface are taken to be uniform. The unsteady, nonlinear and coupled governing equations of the flow are solved using an implicit finite difference scheme. The finite difference scheme is unconditionally stable and accurate. Numerical results are presented with various sets of parameters for both air and water. Transient effects of velocity, temperature and concentration profiles are analyzed. Local and average skin friction, rates of heat and mass transfer are shown graphically. Received on 1 November 1999     

Model studies on the interactions of a Cu(II)-quinone complex with surfactant micelles and DNA explore its induction of apoptosis in human MDA-MB-231 breast adenocarcinoma cells

The interactions of copper complex (CuQ₂) of 1-amino-4-hydroxy-9,10-anthraquinone (QH) with calf thymus DNA, anionic surfactant sodium dodecyl sulfate (SDS), and cationic surfactant cetyltrimethylammonium bromide (CTAB) were investigated in an aqueous solution at physiological pH (7.4). Affinities of such molecule to DNA and surfactant micelles, a model for a biological membrane, are important in determining its biological action. Using different models, various binding parameters were evaluated in both of molecule–DNA interaction and molecule–surfactant interaction. The study showed that hydrophobic interaction plays a major role in the binding of CuQ₂ to surfactant micelles. In addition, the hydrophobic interaction has an important role in the distribution of CuQ₂ between micelle-water phases. Gibbs free energy for the binding and distribution of CuQ₂ between the bulk aqueous medium and surfactant micelles were calculated. In order to correlate the physicochemical properties deciphered from the aforementioned studies with the biological property of the molecule, CuQ₂ was treated with MDA-MB-231 breast adenocarcinoma cells where it was found that the molecule affects the viability of the cancer cells. Fluorescent staining of the treated cells with AO/EB and Hoechst indicated that the CuQ₂ induces apoptosis, suggesting its use in the treatment of breast cancer.     

Synthesis of novel 1,3-thiazin-4-ones by acetylene diester cyclization and their anticancer activities

A novel series of 1,3-thiazin-4-one derivatives containing a piperidyl ring (7–16) were designed and synthesized efficiently by thioamide and acetylene diester cyclization reaction via aminolysis of the ester group and the elimination of an alcohol molecule. The structures of all the novel compounds were established by their FTIR, Mass, ¹H NMR, and ¹³C NMR spectral techniques. The newly synthesized compounds (7–16) were studied for their in vitro anticancer activity against human liver cancer cell lines Hep G2 using MTT assay. The IC₅₀ values of the tested compounds were ranging in between 7.48 ± 0.71 and 56.57 ± 1.37 µM. Further, the apoptosis evaluation by the mitochondrial membrane potential using JC-1 dye was carried out and the results are in good agreement with the cytotoxicity studies.     

A distorted cubic tetranuclear copper(II) phosphonate cage with a double-four-ring-type core

The reaction of Cu2(O2CMe)(4).2H2O with tert-butylphosphonic acid and 3,5-di-tert-butylpyrazole in the presence of triethylamine leads to a high-yield synthesis of the tetranuclear compound [Cu2(3,5-t-Bu2PzH)2(t-BuPO3)2]2 (1). The latter has a distorted cubic cage structure and its core resembles the D4R (double-four-ring) motif found in zeolites. The phosphonate, [t-BuPO3]2-, functions as a dianionic tridentate ligand, while the pyrazole ligands are neutral and are monodentate. The coordination geometry at each copper atom is distorted square planar with a 3O,1N coordination environment. Magnetic measurements on 1 reveal that the chiT product continuously decreases to reach a value very close to zero at 1.8 K, indicating dominant antiferromagnetic interactions between Cu(II) ions that leads to an S=0 ground state. The tetranuclear cage 1 functions as a very effective artificial nuclease in the presence of an external oxidant, magnesium monoperoxyphthalate.     

Water extract of onion catalyst: An economical green route for the synthesis of 2-substituted and 1,2-disubstituted benzimidazole derivatives with high selectivity

An efficient, environmental friendly and substrate controlled method of synthesis of 2-substituted benzimidazole derivatives 3 and 1,2-disubstituted benzimidazole derivatives 4 with high selectivity has been achieved from the reaction of o-phenylenediamine 1 and aldehydes 2 in the presence of water extract of onion and selecting suitable reaction medium. This method is widely applicable for variety of aldehydes such as aromatic/aliphatic/heterocyclic aldehydes and 1,2-diamines to afford 2-substituted benzimidazole derivatives 3 and 1,2-disubstituted benzimidazole derivatives 4 in good to excellent yields (up to 96%). The developed method of water extract of onion catalysis produced 2-substituted benzimidazoles 3 from aromatic aldehydes having electron-withdrawing groups, whereas aromatic aldehydes bearing electron donating groups selectively furnished 1,2-disubstituted benzimidazole 4 derivatives. The process described here has several advantages of cheap, low energy consumption, commercially available starting materials, operational simplicity and nontoxic catalyst. The use of water extract of onion makes this present methodology green and giving a useful contribution to the existing methods available for the preparation of benzimidazole derivatives. In addition, Hammett correlation of substituent constant (σ) vs percentage (%) yield has been established.     

Local non-similarity solution to impact of chemical reaction on MHD mixed convection heat and mass transfer flow over porous wedge in the presence of suction / injection

Combined heat and mass transfer on free, forced, and mixed convection flow along a porous wedge with magnetic effect in the presence of chemical reaction is investigated. The flow field characteristics are analyzed by the Runge-Kutta-Gill scheme with the shooting method as well as the local non-similarity method up to the third level of truncation, which are used to reduce the governing partial differential equations into nine ordinary differential equations. The governing boundary layer equations are converted to a dimensionless form by Falkner-Skan transformations. Because of the effect of suction/injection on the wall of the wedge with buoyancy force and variable wall temperature, the flow field is locally non-similar. Numerical calculations up to the third order level of truncation are carried out as a special case for different values of dimensionless parameters. Effects of the magnetic field strength in the presence of chemical reaction with variable wall temperature and concentration on the dimensionless velocity, temperature and concentration profiles are shown graphically.     

Detection and elimination profile of cathinone in equine after norephedrine (Propalin®) administration using a validated liquid chromatography–tandem mass spectrometry method

Cathinone is the principal psychostimulant present in the leaves of khat shrub, which are widely used in East Africa and the Arab peninsula as an amphetamine-like stimulant. Cathinone readily undergoes metabolism in vivo to form less potent cathine and norephedrine as the metabolites. However, the presence of cathine and norephedrine in biological fluids cannot be used as an indicator of cathinone administration. The metabolism of pseudoephedrine and ephedrine, commonly used in cold and allergy medications, also produces cathine and norephedrine, respectively, as the metabolites. Besides, cathine and norephedrine may also originate from the ingestion of nutritional supplemental products containing extracts of Ephedra species. In Canada, ephedrine and norephedrine are available for veterinary use, whereas cathinone is not approved for human or veterinary use. In this article, the detection of cathinone in equine after administration of norephedrine is reported. To the best of our knowledge, this is the first such report in any species where administration of norephedrine or ephedrine generates cathinone as the metabolite. This observation is quite significant, because in equine detection of cathinone in biological fluids could be due to administration of the potent stimulant cathinone or the nonpotent stimulant norephedrine. A single oral dose of 450 mg norephedrine was administered to four Standardbred mares. Plasma and urine samples were collected up to 120 h after administration. The amount of cathinone and norephedrine detected in post administration samples was quantified using a highly sensitive, specific, and validated liquid chromatography–tandem mass spectrometry method. Using these results, we constructed elimination profiles for cathinone and norephedrine in equine plasma and urine. A mechanism that generates a geminal diol as an intermediate is postulated for this in vivo conversion of norephedrine to cathinone. Cathinone was also detected in samples collected after a single intramuscular administration of 200 mg ephedrine and oral administration of 300 mg ephedrine in equine.

Open image in new window

Figure Electron density structure of cathinone